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Evaluation of distortion of monolithic zirconia crowns under the influence of different preparation designs… Ahmed, Walaa Magdy 2019

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  EVALUATION OF DISTORTION OF MONOLITHIC ZIRCONIA CROWNS UNDER THE INFLUENCE OF DIFFERENT PREPARATION DESIGNS AND SINTERING TECHNIQUES by  Walaa Magdy Ahmed BDS, King Abdulaziz University, 2005 MSc, The University of Toronto, 2012  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF  Doctor of Philosophy in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Craniofacial Science)  THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver)  November 2019  © Walaa Magdy Ahmed, 2019  ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: EVALUATION OF DISTORTION OF MONOLITHIC ZIRCONIA CROWNS UNDER THE INFLUENCE OF DIFFERENT PREPARATION DESIGNS AND SINTERING TECHNIQUES  submitted by Dr. Walaa Magdy Ahmed in partial fulfillment of the requirements for the degree of Doctor of Philosophy  in Craniofacial science  Examining Committee: Dr. Ricardo Carvalho Supervisor  Dr. Christopher Wyatt Supervisory Committee Member  Dr. Anthony McCullagh  Supervisory Committee Member Dr. Edwin Yen University Examiner Dr. Rizhi Wang University Examiner  Additional Supervisory Committee Members: Dr. Tom Troczynski Supervisory Committee Member   iii Abstract Zirconia has seen a marked increase in its use in dentistry. The sintering of soft milled zirconia is accompanied by high shrinkage, approximately 20–30% [1]. Sintering shrinkage is usually estimated as a single value for each blank, and manufacturers do not provide information on how shrinkage percentage is calculated and whether the estimated shrinkage percentage is based on linear or volumetric changes. In order to compensate for sintering shrinkage, the dimensions of the milled frameworks are enlarged by an appropriate factor, which supposedly corresponds to the estimated shrinkage upon sintering [2]. Since dimensional changes are unavoidable during the processing of zirconia [3], the purpose of this series of studies was to understand how different preparation designs may affect dimensional changes during sintering, especially when using different sintering protocols, and how that would affect the fitting of the crown (Chapter 1). A systematic overview of how altering sintering protocol could affect the microstructure, mechanical and optical properties of zirconia material was conducted (Chapter 2). Then a systematic review of literature on the factors affecting the marginal fit of zirconia crowns was assessed qualitatively (Chapter 3). Subsequently, the effects of different preparation designs and sintering protocols on the marginal fit of zirconia crowns were investigated (Chapter 4). Afterwards, the linear and volumetric dimensional differences between the virtual, milled and sintered copings as a result of the two different sintering protocols were measured (Chapter 5). Our search demonstrated that fast sintering improved the optical properties of zirconia but decreased its flexural strength. There was a lack of studies investigating the effects of different sintering protocols on marginal fit and dimensional changes of zirconia prostheses. There was a significant interaction between the crown thickness, finish line width and sintering protocol on the marginal fit of zirconia crowns. There was also a significant interaction between the coping design, processing stage and sintering  iv protocol on linear and volumetric dimensions of zirconia copings. The combined outcome of this series of experiments allowed the proposition of the ideal combination of design and sintering protocol that results in minimal distortion and improves fitting of zirconia crowns.   v Lay Summary   Precise marginal fit is an essential component for the clinical success of dental restorations. Misfit of the prosthesis margin creates a potential space between the restoration and prepared tooth that can accumulate bacterial plaque and consequently jeopardize the longevity of the treatment. There is no existing guideline of the optimum preparation criteria for monolithic zirconia crowns. Therefore, we studied the relationship between marginal adaptation and dimensional changes of zirconia crowns and/or copings to learn the best combination of preparation criteria and sintering protocol that can minimize dimensional changes and therefore reduce the marginal gap of zirconia prostheses.    vi Preface “Zirconia” is used to generally describe the broader group of zirconium oxide materials. The zirconia material used in the experimental studies was IPS e.max ZirCAD LT (Ivoclar vivadent, NY, USA). It is a low translucency 88-95.5% Zirconium oxide ZrO2, 4.5-6% Yttrium oxide Y2O3, less than 5% Hafnium oxide HfO2, less than 1% Aluminum oxide Al2O3, and less than 1% other oxides. IPS e.max ZirCAD LT flexural strength is 1200 MPa and fracture toughness is 5.1 MPa.m1/2.  The work of this thesis has already been published or submitted for publication. This is to confirm that Walaa Magdy Ahmed is the first author in all the publications included in this thesis, as shown below. All the publications were critically reviewed by Professors Ricardo Carvalho and Tom Troczynski. All projects included in this thesis did not need UBC Research Ethics Board Approval.   A version of chapter 2 has been published: Ahmed, W. M., Troczynski, T., McCullagh, A. P., Wyatt, C. C. L., & Carvalho, R. M. (2019). The influence of altering sintering protocols on the optical and mechanical properties of zirconia: A review. J Esthet Restor Dent. doi:10.1111/jerd.12492. Dr. Walaa Magdy Ahmed conducted all the review and wrote the whole manuscript. The manuscript was modified by Dr. Ricardo Carvalho and Tom Troczynski.  A version of chapter 3 has been submitted for publication. It is a systematic review of the literature on the factors affecting the marginal fit of zirconia crowns. The systematic search and selection of studies were done by two independent reviewers, Dr. Walaa Magdy Ahmed and Dr.  vii Arwa Gazzaz. The manuscript was written by Dr. Walaa Magdy Ahmed and critically reviewed by Professor Ricardo Carvalho and Dr. Batoul Shariati.  A version of chapter 4 has been published: Ahmed, W. M., Abdallah, M. N., McCullagh, A. P., Wyatt, C. C. L., Troczynski, T., & Carvalho, R. M. (2019). Marginal discrepancies of monolithic zirconia crowns: The influence of preparation designs and sintering techniques. J Prosthodont. doi:10.1111/jopr.13021. Dr. Walaa Magdy Ahmed wrote the proposal, collected data and conducted all data entry and wrote the manuscript. Atlantis Core file Dentsply Sirona Implants was responsible for titanium custom abutments fabrication by Atlantis Core file digital implant specialist, Canada Western Region. Ivoclar Vivadent, NY, USA was responsible for milling and sintering the zirconia crowns using IPS e.max ZirCAD LT zirconia blanks (Ivoclar Vivadent, NY, USA). Marginal gap measurements were performed by Dr. Walaa Magdy Ahmed at the UBC facility at the Faculty of Dentistry using the optical microscope and imageJ software. Statistical analysis of the research data was performed by or under the consultation of Biljana J. Stojkova at the University of British Columbia, Department of Statistics, The Applied Statistics and Data Science Group (ASDa). The manuscript was proofread and modified by Dr. Mohamed-Nur Abdallah, Dr. Ricardo Carvalho, Tom Troczynski, and Dr. Anthony McCullagh. My research committee members, Dr. Ricardo Carvalho, Tom Troczynski, Dr. Anthony McCullagh and Dr. Chris Wyatt, have substantially contributed to the manuscript from presenting ideas, modifying approaches, formatting and presentation. This project received the American College of Prosthodontic Educational Research Fellowship award in 2016. This study was presented at UBC Research Day 2019 and awarded the PhD first place. It was also presented in two USA competitions, the Sharry competition of the American College of Prosthodontists annual meeting  viii 2018 (awarded third place) and the Pacific Coast Society of Prosthodontics 2019 (awarded second place).    A version of chapter 5 was submitted for publication. Atlantis Core file Dentsply Sirona Implants was responsible for titanium custom abutment fabrication by Atlantis Core file digital implant specialist, Canada Western Region. Ivoclar Vivadent, NY, USA was responsible for milling and sintering the zirconia copings using IPS e.max ZirCAD LT zirconia blanks (Ivoclar Vivadent, NY, USA). The linear and volumetric measurements were performed by Dr. Walaa Magdy Ahmed at the UBC facility at Faculty of Dentistry using the Trios intra-oral scanner and Meshmixer software. The statistical analysis of the research data was performed by or under the consultation of Biljana J. Stojkova at the University of British Columbia, Department of Statistics, The Applied Statistics and Data Science Group (ASDa). This project received the American College of Prosthodontic Educational Research Fellowship award in November 2019.  Chapter 6 includes the overall discussion, conclusions, limitations and future direction of this thesis. Some repetition of information did occur in terms of literature review, discussion and conclusions. Efforts were made to minimize this repetition and make each chapter stand alone as well as maintaining the coherence of the whole thesis.      ix Table of Contents  Abstract ......................................................................................................................................... iii Lay Summary .................................................................................................................................v Preface ........................................................................................................................................... vi Table of Contents ......................................................................................................................... ix List of Tables ................................................................................................................................xv List of Figures ........................................................................................................................... xviii List of Abbreviations ................................................................................................................ xxii Acknowledgements ....................................................................................................................xxv Dedication ................................................................................................................................. xxvi Chapter 1: Introduction ................................................................................................................1 1.1 History of Zirconia ..........................................................................................................1 1.2 Properties of the Zirconia ................................................................................................2 1.2.1 Microstructural Properties ...................................................................................... 2 1.2.2 Physical Properties .................................................................................................. 4 1.2.2.1 Zirconia Fracture Toughness .............................................................................. 4 1.2.2.2 Wear of Zirconia and Antagonists in Dentistry .................................................. 5 1.2.3 Chemical Properties ................................................................................................ 7 1.2.3.1 Low Thermal Degradation (LTD) or Hydrothermal Aging ................................ 7 1.2.4 Zirconia Biocompatibility ....................................................................................... 8 1.2.5 Zirconia Optical Properties ..................................................................................... 9 1.3 Types of Zirconia in Dentistry .......................................................................................11  x 1.3.1 Tetragonal Zirconia Polycrystals (TZP; e.g., Y-TZP, Ce-TZP) ........................... 11 1.3.2 Partially Stabilized Zirconia (PSZ; e.g., Ca-PSZ, Mg-PSZ, Y-PSZ) ................... 12 1.3.3 Zirconia Toughened Alumina (ZTA).................................................................... 13 1.3.4 Graded Zirconia .................................................................................................... 13 1.4 Manufacturing of the Zirconia Prostheses .....................................................................13 1.4.1 Soft Machining of Pre-sintered Blanks ................................................................. 13 1.4.2 Hard Machining of 3Y-TZP.................................................................................. 15 1.5 Sintering Zirconia ..........................................................................................................16 1.6 The Clinical Studies of Zirconia-Based Crowns ...........................................................17 1.6.1 Zirconia-based Crowns ......................................................................................... 17 1.6.2 Full-Contoured Zirconia Crowns .......................................................................... 18 1.7 Post-Sintering Marginal Fit of Zirconia Crowns ...........................................................19 1.7.1 Acceptable Marginal Gap ..................................................................................... 19 1.7.2 Fit Terminology .................................................................................................... 20 1.7.3 Marginal Gap and Secondary Caries .................................................................... 22 1.8 Gap in Knowledge .........................................................................................................23 1.9 Specific Aims and Rationales ........................................................................................25 1.9.1 Specific Aim 1 ...................................................................................................... 25 1.9.1.1 Rationale for Aim 1 .......................................................................................... 25 1.9.2 Specific Aim 2 ...................................................................................................... 26 1.9.2.1 Rationale for Aim 2 .......................................................................................... 26 1.9.3 Specific Aim 3 ...................................................................................................... 26 1.9.3.1 Rationale for Aim 3 .......................................................................................... 26  xi 1.9.3.2 Null hypothesis for Aim 3................................................................................. 26 1.9.4 Specific Aim 4 ...................................................................................................... 27 1.9.4.1 Rationale for Aim 4 .......................................................................................... 27 1.9.4.2 Null hypothesis for Aim 4................................................................................. 27 1.9.5 Specific Aim 5 ...................................................................................................... 27 1.9.5.1 Rationale for Aim 5 .......................................................................................... 27 1.9.5.2 Null hypothesis for Aim 5................................................................................. 28 Chapter 2: The Influence of Altering Sintering Protocols on the Optical and Mechanical Properties of Zirconia: A Review ...............................................................................................29 2.1 Purpose ..........................................................................................................................29 2.2 Materials and Methods ..................................................................................................29 2.2.1 Search Strategy ..................................................................................................... 29 2.2.2 Inclusion/Exclusion Criteria ................................................................................. 30 2.2.3 Extracted Data ....................................................................................................... 30 2.3 Results ............................................................................................................................31 2.4 Discussion ......................................................................................................................35 2.4.1 Effect of Altering Sintering Time/Temperature on the Optical Properties of Zirconia .. .............................................................................................................................. 36 2.4.2 Effect of Altering Sintering Time/Temperature on the Mechanical Properties of Zirconia .. .............................................................................................................................. 39 2.5 Conclusions ....................................................................................................................41 Chapter 3: Fit of Tooth-supported Zirconia Single Crowns - A Systematic Review of the Literature ......................................................................................................................................43  xii 3.1 Purpose ..........................................................................................................................43 3.2 Materials and Methods ..................................................................................................43 3.2.1 Search Strategy ..................................................................................................... 43 3.2.2 Inclusion/Exclusion Criteria ................................................................................. 45 3.2.3 Selection Criteria .................................................................................................. 45 3.2.4 Data Extraction ..................................................................................................... 47 3.2.5 Quality Assessment ............................................................................................... 48 3.3 Search Results ................................................................................................................48 3.3.1 Factors Affecting Zirconia Marginal Fit ............................................................... 48 3.3.2 Methods Used for Measuring Marginal and Internal Fit of Zirconia Crowns ...... 49 3.3.3 Description of the Selected Studies ...................................................................... 49 3.4 Discussion ......................................................................................................................61 3.5 Conclusions ....................................................................................................................69 Chapter 4: Influence of Crown Design and Sintering Protocol on Marginal Fit of Monolithic Zirconia Crowns...........................................................................................................................71 4.1 Purpose ..........................................................................................................................71 4.1.1 Fabrication of the Master Dies .............................................................................. 71 4.1.2 Crown Fabrication ................................................................................................ 74 4.1.3 Experimental Groups ............................................................................................ 75 4.1.4 Sintering Protocol ................................................................................................. 76 4.1.5 Measurement of the Marginal Discrepancy .......................................................... 79 4.1.6 Statistical Analysis ................................................................................................ 82 4.2 Results ............................................................................................................................83  xiii 4.3 Discussion ....................................................................................................................103 4.4 Conclusions ..................................................................................................................107 Chapter 5: Dimensional Changes of Yttria-stabilized Zirconia under Different Preparation Designs and Sintering Protocols ...............................................................................................108 5.1 Purpose ........................................................................................................................108 5.2 Material and Methods ..................................................................................................109 5.2.1 Fabrication of the Master Dies ............................................................................ 109 5.2.2 Coping Fabrication.............................................................................................. 111 5.2.3 Experimental groups ........................................................................................... 114 5.2.4 Sintering Procedure Protocol .............................................................................. 116 5.2.5 Measurement of the Dimensional Changes ........................................................ 118 5.2.6 Statistical Analysis .............................................................................................. 120 5.3 Results ..........................................................................................................................121 5.3.1 Primary Outcome: Interaction Between Coping Design (Group), Sintering (Sintering) and Processing Stage (Stage) on Linear Measurements (LM) ......................... 121 5.3.2 Secondary Outcome: Interaction Between Coping Design (Group), Sintering (Sintering) and Processing Stage (Stage) on Volumetric Measurements (VM) ................. 135 5.4 Discussion ....................................................................................................................148 5.5 Conclusions ..................................................................................................................152 Chapter 6: Summary and Conclusion......................................................................................153 6.1 Limitations ...................................................................................................................157 6.2 Future Directions .........................................................................................................158 References ...................................................................................................................................160  xiv Appendix .....................................................................................................................................177   xv List of Tables Table 1-1 Factor Influence the Optical Properties of Zirconia ....................................................... 9 Table 1-2 Fit Terminology according to Holmes et al. [78] ......................................................... 21 Table 2-1 Summary of the 11 included articles (see Appendix A)............................................... 32 Table 3-1 Search strategy in MEDLINE applied for this review ................................................. 44 Table 3-2 Search strategy in Embase applied for this review ....................................................... 44 Table 3-3 A descriptive table for excluded articles ...................................................................... 47 Table 3-4 Summary of the articles included for final analysis ..................................................... 49 Table 4-1 Experimental groups according to the different combinations of finish line widths, abutment length, crown thickness and sintering protocol. ............................................................ 75 Table 4-2 Likelihood ratio values from testing the effect of the Finish line × Crown thickness × Sintering ........................................................................................................................................ 86 Table 4-3 Vertical marginal gaps mean estimates for different combinations of CrownThickness (CT) × Finishline depending on the sintering process .................................................................. 87 Table 4-4 ANOVA table for Model 2 ........................................................................................... 89 Table 4-5 Multiple comparisons between all the different combinations of finish line and sintering for each crown thickness (CT), adjusted by false discovery rate (FDR) method for multiple comparisons within each level of crown thickness. ....................................................... 90 Table 4-6 Likelihood ratio values from testing the effect of the Finish line × Crown thickness × Sintering × Surface interactions (Case 2) on the vertical marginal gap following Model 1` and Model 2`. ....................................................................................................................................... 94 Table 4-7 ANOVA test for Model 2`. ........................................................................................... 95  xvi Table 4-8 Vertical marginal gap mean estimates for different combinations of CrownThickness × Finishline × Sintering × Surface (case 2). ..................................................................................... 96 Table 5-1 Experimental groups according to the coping designs ............................................... 115 Table 5-2. Descriptive table of the average percentage change between each of the stages for each combination of the Group and Sintering. Columns LM_St0,LM_St1,LM_St2 correspond to average LM for each stage, and for each combination of Group and Sintering. ........................ 123 Table 5-3. Descriptive table of the average percentage change between each of the stages for each Sintering method averaged over the 6 Groups. Columns LM_St0,LM_St1,LM_St2 correspond to average LM for each stage, grouped by sintering method while taking average over the 6 groups. ........................................................................................................................ 126 Table 5-4 ANOVA type 3 table to test the significance of the three-way interaction from the linear model. Linear measurement ~ Stage+Group+Sintering+Stage  Group+Stage  Sintering+Group  sintering+Stage  Group  Sintering + RE(Sample) + RE(Distance) ......... 128 Table 5-5 Estimated coefficients for the three-way interaction, three two-way interactions and main effects from the linear model mixed effect model: Linear measurement ~ Stage+Group+Sintering+Stage  Group+Stage  Sintering+Group  sintering+Stage  Group  Sintering + RE(Sample)+ RE(Distance) ..................................................................................... 129 Table 5-6. Descriptive table of the average percentage change between each of the stages for each combination of the Group and Sintering. Columns Vol_St0,Vol_St1,Vol_St2 correspond to average Volume for each stage, and for each combination of Group and Sintering. ................. 137 Table 5-7. Descriptive table of the average percentage change between each of the stages for each Sintering method averaged over the 6 Groups. Columns Vol_St0,Vol_St1,Vol_St2  xvii correspond to average Volume for each stage, grouped by sintering method while taking average over the 6 groups. ........................................................................................................................ 140 Table 5-8 ANOVA Type 3 table to test the significance of the three-way interaction from the linear mixed effect model. The model is specified with Volume as response and the three-way interaction of interest Stage  Group  Sintering, three two-way interactions Stage  Group, Stage  Sintering and Group  Sintering, main effects for Stage, Group and Sintering and random effect for the Sample to account for the correlated observations within a Sample ....... 142 Table 5-9 Estimated coefficients for the three-way interaction, three two-way interactions and main effects from the linear model mixed effect model specified in Table 5-4. ........................ 143   xviii List of Figures Figure 1-1 Zirconia Three Allotropic Phases [16]. ......................................................................... 3 Figure 1-2 Transformation Toughness Mechanism adapted from Material science and engineering textbook, Callister [19]. As the t-m occurs at the crack propagation front, the expansion caused by the transformation compresses the crack front and delays its propagation. . 5 Figure 1-3 Cold isostatic pressing fabrication of partially sintered zirconia blanks [46]. ............ 14 Figure 1-4 Hot isostatic pressure machining for fabrication of fully sintered zirconia [47]. ....... 15 Figure 1-5: Fit definitions according to Holmes et al. [66]. ......................................................... 22 Figure 3-1 PRISMA flow diagram to identify the included studies in the review ....................... 46 Figure 4-1 Illustrations showing the digital fabrication process of the core file abutment. A dental laboratory scanner was used to scan the model and Atlantis FLO to order the abutments (Left). Dental Wing software was used to import the core files and design the six master abutments individually (Right). ...................................................................................................................... 72 Figure 4-2 Upper row: Photographs showing the titanium abutment (Left: tall abutment (5.7mm); right: short abutment (5.0mm). Lower row: Illustrations showing the relationship between the abutment length and crown thickness (Left: tall abutment and thin crown; right: short abutment and thick crown). .......................................................................................................................... 73 Figure 4-3 Digitally designed monolithic zirconia crown. Example showing the different parameters used to set the cement thickness marginally and internally (Left). Example showing the software interface for designing the different crown dimensions (Right). ............................. 74 Figure 4-4  Schematic diagram illustrating the different experimental groups. “Ti” refers to titanium abutments. ....................................................................................................................... 76  xix Figure 4-5 Standard and fast sintering protocols following the manufacturer’s recommendations for sintering IPS e.max ZirCAD LT. The standard program is 9hr in total, while the fast program is 3 hr 30 min in total. ................................................................................................................... 77 Figure 4-6 An image illustrating the rotating measuring chuck using an alignment clamp and 500g load. ...................................................................................................................................... 80 Figure 4-7 Measurement locations................................................................................................ 81 Figure 4-8 Buccal marginal gap image taken by the digital microscope and measured using imageJ software. ........................................................................................................................... 82 Figure 4-9 Boxplots of vertical marginal gap values from the different Crown thickness × Finishline × Sintering combinations. ............................................................................................ 84 Figure 4-10 Interaction plot for effect of Length × Finishline × Sintering on Marginal gap. Points on the plot represent mean values of the Marginal gap for each combination of Length × Finishline × Sintering. Dotted lines represent standard errors of the respective mean estimates. 85 Figure 4-11 Estimated mean vertical marginal gap values from Case I, Model 2 for each combination of CrownThickness × Finishline × Sintering to reflect Table 4-3. .......................... 88 Figure 4-12 Boxplots of vertical marginal gap values from the different crown thickness × finish line × sintering × surface interactions. .......................................................................................... 93 Figure 4-13 Estimated mean vertical marginal gap values from Case II, Model 2` by the different Crown Thickness × Finish line × Sintering × Surface combinations. ........................................ 102 Figure 5-1. Illustrations showing the digital fabrication process of the core file abutment. A dental laboratory scanner was used to scan the model and Atlantis FLO was used to order the abutments (Left). Dental Wing software was used to import the core files and design the master abutment. ..................................................................................................................................... 110  xx Figure 5-2 Photograph showing the Atlantis titanium abutment. ............................................... 111 Figure 5-3 Schematic example showing the different parameters used to set the cement thickness marginally and internally in the digitally designed monolithic zirconia coping (all dimensions in mm). ............................................................................................................................................ 111 Figure 5-4 Schematic example showing the software interface for designing the different coping dimensions. ................................................................................................................................. 112 Figure 5-5 Schematic illustrating AB, BC, CD, DA linear measurements in mm. .................... 113 Figure 5-6 An image illustrating how the samples were held by the veneer stick during scanning process......................................................................................................................................... 114 Figure 5-7 Experimental groups with different coping dimensions and the four posts showing in Meshmixer software.................................................................................................................... 116 Figure 5-8 Standard and fast sintering protocols following the manufacturer’s recommendations. The standard program is 9hr in total, while the fast program is 3 hr 30 min in total. ................ 117 Figure 5-9 Schematic illustrating the methodology of the linear measurements DA a) at the design stage, b) at the milling stage, and c) at the sintering stag of G1 in Meshmixer software.119 Figure 5-10 Schematic illustrating the methodology of the volumetric measurements a) at the design stage, b) at the milling stage, and c) at the sintering stage of G3 in Meshmixer software...................................................................................................................................................... 120 Figure 5-11. Linear measure (mm) median by Group, Sintering and Stage. .............................. 121 Figure 5-12. Interaction plot of Linear measure (mm) by Group  Sintering  Stage. Points on the plot represent mean values of the LM for each combination of Group  Stage. Vertical dotted lines represent standard errors of the respective mean estimates. .............................................. 122  xxi Figure 5-13. Estimated mean Linear measure (mm) by Group  Sintering  Stage interaction from the model. ........................................................................................................................... 130 Figure 5-14 Estimated marginal means of Linear measure for each combination of sintering within a group at each stage and their respective 95% confidence intervals. ............................. 132 Figure 5-15 Estimated pairwise stage difference in Linear Measure and their respective 95% confidence intervals. ................................................................................................................... 133 Figure 5-16 Estimated pairwise stage differences in Linear measure for each combination of group and sintering and their respective 95% confidence intervals. .......................................... 134 Figure 5-17 Volume by Group, Sintering and Stage. ................................................................. 135 Figure 5-18 Interaction plot of Volume measure by Group  Sintering  Stage. Interaction plot for effect of Group  Stage on Volume. Points on the plot represent mean values of the VM for each combination of Group  Stage. Dotted lines represent standard errors of the respective mean estimates. SS and FS are parallel except at G4. ................................................................ 136 Figure 5-19 Estimated mean Volume by Group  Sintering  Stage interaction from the model...................................................................................................................................................... 144 Figure 5-20 Estimated marginal means of Volume for each combination of sintering within a group at each stage and their respective 95% confidence intervals. ........................................... 145 Figure 5-21 Estimated pairwise stage difference in Volume and their respective 95% confidence intervals. ...................................................................................................................................... 146 Figure 5-22 Estimated pairwise stage differences in Volume for each combination of group and sintering and their respective 95% confidence intervals. ............................................................ 147  xxii  List of Abbreviations .stl                  STereoLithography  ∆E                       color difference 3D                    Three dimensional AMG               Absolute marginal gap  ANOVA           Analysis of variance  c                       The cubic phase of zirconia  CAD/CAM      Computer-aided design/computer-aided manufacturing CaO                  Calcium oxide Ce2O3               Cerium oxide CI                     Confidence Interval CIELab (L* a* b*) color coordinates  CR                       contrast ration CS                    Conventional sintering DB                    Distobuccal DL                    Distolingual F.S                      Flexural strength  FCZ                  Full-contoured zirconia  FDP                  Fixed dental prosthesis FS                     Fast sintering FSZ                   fully sintered zirconia  G.S.                     grain size h                          hour   xxiii HIP                   Hot isostatic pressure I.F.                   Internal fit  LM                   Linear measurements  LTD                 Low-thermal degradation m                      The monoclinic phase of zirconia  MB                   Mesiobuccal MCC                 Metal ceramic crowns MgO                 Magnesium oxide  MG                  Marginal gap  ML                   Mesiolingual  MS                      microwave  PSZ                   partially sintered zirconia  Ra                        roughness  SEM                Scanning electron microscope  SS                    Standard sintering t                        The tetragonal phase of zirconia  t/T                    time/Temperature rate Tc                        thermocycling Tooth #46        Mandibular right first molar TP                      Translucency parameter  VM                  Volumetric measurements  Y2O3                 Yttria, Yttrium oxide YTZP                  yttria-stabilized tetragonal zirconia polycrystalline  xxiv Zr                     Zirconia    xxv Acknowledgements I would like to thank my great mentor and supervisor, Dr. Ricardo Carvalho, for his valuable guidance, encouragement, and mentoring throughout my last six years and for making me a competent future researcher and educator. I offer my enduring gratitude to my advisory committee, Dr. Tom Troczynski, Dr. Anthony McCullagh and Dr. Chris Wyatt, for their continuous guidance throughout my research.  I thank Dr. Joy Richman for allowing me to use her microscopes at UBC facilities. I would also like to thank Biljana J. Stojkova at the University of British Columbia, Department of statistics, The Applied Statistics and Data Science Group (ASDa) for helping me with the statistical analyses. I greatly appreciate the generous financial support and educational sponsorship from King Abdulaziz University (KAU), Saudi Arabia. I deeply appreciate the generous financial support of the American College of Prosthodontics Education Foundation award (ACPEF), USA for the fellowship award in 2016, and the invaluable support and trust of Ivoclar Vivadent company for providing the zirconia material and further milling the crowns and copings at no cost. I would also like to thank the Canadian Dental Specialties Association (CDSA), who recognized my participation in the Sharry Competition and generously awarded me with a CDSA travel award 2018.       xxvi Dedication I dedicate this work to: my beloved mother, Dr. Awatif Jamil Khogeer, for everything she has done to make me the person I am today. For always being my inspiration and strength even after she left our world. For all the days and nights she suffered to make me and my brothers who we are. Without her kindness, care and patience, we would not have reached this high level of education. May God bless her and reward her for her good deeds. the sweetest father, Dr. Magdy Abdulhamid Eissa, for his endless love, support and prayers. For planting the courage and strength in my soul. For being supportive all the time.  my lovely husband and best friend, Dr. Khaled Ahmed Fawaz, for his endless love and sacrifice. For sharing the happiness and hardship with me, believing in me and pushing me always forward to be the best I can.  my kids and sweethearts Lilian, Lamis, Salma and Sara, for making this life meaningful and bright and enduring my educational journey from the first breath of their life. my brothers Haitham, Wael, Hani, and Hossam, for their support and guidance.       Chapter 1: Introduction 1.1 History of Zirconia  Zircon is a well-known gemstone from ancient times. The word zircon was originally derived from the Arabic work “Zargon,” which means golden color. Chemically, zirconia is referred to as zirconium oxide and technically, it is a ceramic material. Zirconium oxide is relatively abundant in nature (about 0.02% of the earth’s crust) [4]. In 1789, the German chemist Martin Heinrich Klaproth identified zirconia (the metal dioxide), ZrO2, in a reaction after heating some gems. Zirconium oxide has been used for long time as a pigment for ceramic when mixed with other rare earth oxides [5]. It is insoluble in water but dissolves in H2SO4 and HF. For a long time, zirconia has been used in industry for manufacturing extrusion dyes, valves and port liners for combustion engines. It has also been used as zirconia blades for cutting and in fuel cells and oxygen sensors. Helmer and Driskell (1969) published the first paper concerning biomedical applications of zirconia and Christel (1988) published the first paper concerning zirconia used to manufacture ball heads for total hip replacement. The fate of zirconia for hip replacement was marked by a great incidence of premature failure of ceramic ball heads made of Yttria-stabilized zirconia between 2000 and 2002. The prosthesis was produced by Saint Gobain Desmarquest and marked with the name Prozyr. They failed prematurely due to the change in the processing procedure (from batch to tunnel furnace), which resulted in increased monoclinic content [5]. The poor outcome in the orthopedic field practically suppressed the use of zirconia for medical purposes, with no other attempts recorded since then.  Parallel to that, in 1999, during an international symposium in Munich, zirconium dioxide was considered to fulfill all the requirements for an ideal restorative material in dentistry because of its good chemical, dimensional and mechanical properties. Since then, dentistry began to deal  2 with zirconia as a potential material for dental applications. Zirconia use has increased in clinical applications in dentistry since 2004, mostly because of its white color, strength and functional outcomes. Zirconia has been increasingly used for multiple dental applications, such as the fabrication of all-ceramic copings, endodontic posts [6], fixed partial prostheses [7, 8], and full-arch dental prostheses[9], as well as implant abutments and implants [10]. Clinical studies have shown that zirconia-based prostheses may serve as viable long-term restorations [8, 11-14]. However, technical problems associated with the clinical performance of zirconia crowns and fixed dental prostheses have been reported, in particular, chipping of the veneering porcelain when applied to zirconia framework structures and loss of retention [8, 11-13]. Attempts to minimize the chipping of veneering porcelain by milling the veneers and frameworks separately and subsequently luting them with either luting agent or using fusing firing (CAD on) has not been quite sufficient to address the chipping concerns [15]. Another attempt to overcome the veneer chipping problem was the introduction of zirconia in the form of fully anatomical contoured monolithic prostheses intended to be used without veneering porcelain. These have been generically known as monolithic zirconia crowns in the field of prosthodontics. 1.2 Properties of the Zirconia  1.2.1 Microstructural Properties   Zirconia is a polymorphic material that exists in three allotropes: the monoclinic phase (m), which is stable at room temperature up to 1170C; when it converts to the tetragonal phase (t), which is stable up to 2370C; and then transforms to the cubic phase (c), which exists up to its melting point of 2680C (Figure 1-1). This two-way, temperature-driven phase transformation is  3 accompanied by significant changes in mechanical properties, with greater strength at the tetragonal phase, followed by the cubic phase.  For dental prosthesis applications, stabilizing zirconia at the tetragonal phase is desirable because cooling to room temperature is associated with 4-5% volumetric expansion that causes severe cracking, which ultimately leads to catastrophic failure of the material and consequently of the prosthesis. Because of that, blending zirconia with stabilizing oxide “dopants” has been shown to stabilize zirconia in tetragonal or cubic phases at room temperature, therefore maintaining the improved mechanical, thermal and electrical properties and allowing its use for dental applications and others. Effective dopants include Magnesium oxide (MgO), Yttrium oxide (Y2O3, Yttria), Calcium oxide (CaO), and Cerium oxide (Ce2O3).    Figure 1-1 Zirconia Three Allotropic Phases [16].   4 1.2.2 Physical Properties  1.2.2.1 Zirconia Fracture Toughness Zirconia is regarded as one of the toughest materials available, and certainly the toughest of the ceramic-like materials in dentistry. Ironically, the advantage of phase transformation from tetragonal to monoclinic is that the resultant expansion puts a crack into compression and retards its growth, thereby enhancing the fracture toughness of the material. Zirconia ceramics are toughened by the process of ‘crack shielding,’ which involves the formation of a microcracked zone around a propagating crack, thus reducing the crack-tip stress and generating a layer of compressive stresses that eventually dissipates the energy of the propagating crack [17] (Figure 1-2). Residual stresses arise when zirconia is sintered at high temperature and then cooled down to room temperature for practical dental use; fast cooling rates and/or coupling with other veneering materials having a different coefficient of thermal expansion (CTE) leads to larger residual stresses. Another factor that triggers tetragonal to monoclinic (t→m) phase transformation is the milling process of zirconia and adjusting zirconia occlusal and/or intaglio surfaces of the prosthesis before insertion [18].  Although zirconia’s self-toughening mechanism is regarded as advantageous to prevent a catastrophic fracture under stress, the transformation from tetragonal to monoclinic phase (t→m) is irreversible and will ultimately render the material weaker, with longer-term unpredictable consequences. The t→m phase transformation is regarded as the major drawback of zirconia material. Besides localized stress, phase transformation can also be caused by a phenomenon known as low-thermal degradation (LTD) or hydrothermal aging [18].    5  Figure 1-2 Transformation Toughness Mechanism adapted from Material science and engineering textbook, Callister [19]. As the t-m occurs at the crack propagation front, the expansion caused by the transformation compresses the crack front and delays its propagation.   1.2.2.2 Wear of Zirconia and Antagonists in Dentistry Full contoured zirconia restorations caused concern about the wear of the antagonists because of the hardness of Y-TZP that was found to be double the hardness of most of porcelains [8]. The wear of zirconia antagonists depends on the material used as well as environmental factors. Materials’ factors such as fracture toughness, internal pores, and surface flaws and/or defects may induce accelerated wear of antagonists [20]. The surface textures also play an important role in wear of antagonists. The effect of full zirconia restoration on abrasion of antagonistic teeth is an issue of great clinical significance from the standpoint of prolonged stability and safety of the occlusion when zirconia is used for the occlusal surface [20]. The adjustment of the occlusion at the moment of delivering a ceramic restoration is crucial since a  6 rough surface as a result of the adjustment may increase wear of the opposing tooth and restorative materials.  There is currently a shortage of comprehensive, fundamental studies that quantitatively and qualitatively evaluate the wear pattern of zirconia crowns against other restorative materials, and the effect of the sintering process on the resultant wear characteristics. Plus, there is a lack of clinical knowledge concerning the effect of the wear mechanism of monolithic zirconia crowns due to the effect of low-thermal degradation of zirconia. Two studies evaluated the wear mechanism of anatomical contoured zirconia (polished vs. glazed) using 2-body wear against enamel [21, 22]. They found that polished zirconia yielded less antagonist wear compared to glazed zirconia. A different study measured the wear of antagonist enamel against polished, autoclave-aged zirconia and found no significant difference in the roughness of aged zirconia compared to non-aged zirconia [23]. Translucent and shaded monolithic zirconia resulted in less wear to the antagonist than monolithic lithium disilicate, veneering porcelain or enamel specimens [21, 24]. Furthermore, Park et al. reported less wear of the antagonistic tooth against different CAD/CAM anatomic contour zirconia compared to veneered ceramic, and that staining and glazing the zirconia substructure caused more antagonistic tooth wear than polishing [22].  Polished monolithic zirconia caused a significantly lower wear rate on enamel antagonists as well as within the material itself compared to the glazed monolithic specimens [21], but developed higher rates of enamel cracks [25]. More interestingly, polished zirconia specimens that were glazed by using a glaze spray showed less enamel wear than airborne-particle abraded zirconia that was glazed using a layering technique with glaze ceramic [25]. Surface roughness after polishing with diamond paste and glazing showed zirconia to be smoother than feldspathic porcelain. Moreover, no statistical difference was found between the surface roughness values of  7 polished with diamond paste and glazing.  These results indicated that zirconia might have a possibility to present a smooth surface after occlusal adjustment and loading [20]. Stawarczyk et al. presented SEM images of the enamel surface after the loading test and showed an increase cracks on the enamel antagonist [25]. This result suggests a disadvantage of full zirconia restorations resulting from the discrepancy of hardness between the substrates. Further investigation is required for this point. 1.2.3 Chemical Properties 1.2.3.1 Low Thermal Degradation (LTD) or Hydrothermal Aging LTD is defined as the spontaneous t→m transformation occurring over time at low temperature and in the presence of fluids. In this case, transformation is not triggered by the local stress produced at the tip of an advancing crack [4]. Although LTD has been investigated and identified as the major cause of failures of zirconia implants (femur head replacements) in orthopedics, it has been poorly investigated and highly disregarded as a potential problem for zirconia in dental applications [18, 26, 27].  In the current literature, there are three informed speculations that investigated the aqueous attack of Y-TZP ceramics and explained the mechanisms of the low-thermal degradation phenomenon. The first speculation was proposed by Lang et al. [26] and claimed that the reaction between water vapor and yttrium oxide (Y2O3) forms clusters rich in yttrium hydroxide (Y(OH)3), which leads to depletion of the stabilizer in the surrounding zirconia grains and allows the transformation from tetragonal to monoclinic phase. The second speculation was explained by Yoshimura et al. [27] who suggest that diffusion of water vapor leads to stress accumulation that breaks the Zr-O bond and causes subsequent lattice defects acting as a nucleating agent for subsequent tetragonal to monoclinic transformation [27]. The third and most recent proposed  8 mechanism is by Chevalier et al. [18], who theorize that O2- originating from water desiccation fills the oxygen vacancies in zirconia grains and is believed to be the cause of destabilization and change of the lattice parameters.  Despite potential long-term problems derived from LTD, zirconia has been shown to have excellent strength and fracture toughness in short-term laboratory testing [5]. Many factors can affect the LTD, including stabilizer type and content, residual stress and grain size [28]. Several solutions were proposed in the literature to minimize the LTD of 3Y-TZP, including adding small amounts of silica [29], using yttria coating rather than co-precipitated powder, reducing the particle size [30] and increasing the stabilizer content or by the formation of composites with Al2O3 Co-doping of Ce-nitrate by liquid infiltration [31]. Zirconia hydrothermal degradation was reduced by selecting a specific pre-sintering temperature and optimized solutions.  1.2.4 Zirconia Biocompatibility  Biocompatibility and chemical stability are highly important properties in dental materials. Biocompatibility is the ability of a material to provide successful clinical service in a host without producing allergic and/or toxic reactions in the surrounding tissues or adverse systemic reactions [32]. Zirconia ceramics have been reported not to have potential toxic or genotoxic effects and to present satisfactory tissue responses [5]. The biocompatibility of zirconia has been evaluated in vivo and in vitro. The first in vivo publication dates back to 1969 [33], while the first in vitro publication was in 1990 [34]. In vitro studies concluded that zirconia has no toxic effects on cell cultures or when in contact with blood cells. The in vivo studies studied the biocompatibility when implementing zirconia in bone and soft tissue and showed no cytotoxicity in the soft tissue and no bone reaction.  9 1.2.5 Zirconia Optical Properties  Zirconia is an opaque monochromic material. Esthetic characteristics of zirconia restoration are related to its optical properties, which include translucency, contrast ratio, color, direct transmittance of light, and opalescence. Factors influencing the optical properties of zirconia are summarized in Table (1-1) [35].   Table 1-1 Factor Influence the Optical Properties of Zirconia Translucency ceramic brand and thickness, presence of cubic phase, amount and type of additives, number of pores, ceramic shade, sintering time and temperature, primary grain size, refractive index, atmospheric conditions while sintering, surface roughness, contrast ratio, acidic medium, and staining Contrast ratio zirconia brand and thickness, grain size, sintering temperature and duration, and translucency Color the number of firings, ceramic brand, ceramic thickness, cement color, cement thickness, abutment color, sintering temperature and duration, and number of coloring liquid applications Opalescence the number of coloring liquid applications, and ZrO2 and Y2O3 concentrations  Zirconia opacity can be caused by its microstructural properties, high refractive index (2.20), larger particle size than visible light wavelengths (380-780), different refractive indices between the zirconia matrix and the second phase such as impurities (sintering aids), defects (oxygen vacancies) or pore-refractive indices, which can lead to discontinuity of refractive indices at the grain boundaries [36].    10 Because of zirconia’s opacity, two principal techniques have been developed for coloring zirconia restorations to overcome this esthetic problem and to decrease the zirconia opacity. One technique is by adding metal oxides (pigments) to the Y-TZP powder before pressing the milling blocks and then sintering it. In this method, the color of the zirconia blocks is determined at the time of block fabrication and therefore, it is called pre-colored zirconia. In the other technique, milled zirconia restorations are immersed in coloring liquids as chloride solutions (rare earth elements) before sintering to achieve desired shade [37]. Recently, advanced protocols have been developed to reduce the opacity of zirconia by reducing the particle size below the visible wavelength to keep its grain size small, ideally under 100 nm, because when the grain size decreases below approximately a micron, the effect of pores is significantly reduced [38]. Another protocol is to substitute the 0.1-0.25 wt% alumina sintering aid with 0.2mol% La2O3 to reduce zirconia opacity [39].  One additional approach is to replace some tetragonal zirconia grains with optically isotropic cubic zirconia particles by increasing the yttria content to diminish grain boundary light scattering and make it fully stabilized zirconia [39]. However, the cubic zirconia is weaker and more brittle than its tetragonal counterpart [39]. Finally, the opacity can be reduced by optimizing the heat treatment conditions to reduce the oxygen vacancies while avoiding the introduction of porosity. This is because zirconia will contain a high concentration of oxygen vacancies when sintered in an environment of reduced oxygen vacancies, which act as light scattering centers and at the same time introduce porosity. In addition to that, when zirconia is heat treated in air after sintering, it will restore oxygen into 3Y-TZP crystals and will also introduce porosity to the material due to the coalescence of vacancies in large concentrations at high temperatures [40].   11 It has been documented that the aging process affects the optical properties of zirconia and glass ceramic. Over time, the transparency decreases, and the ceramic material becomes more opaque (higher contrast ratio), darker, reddish and yellowish. The translucency parameter of zirconia was affected by lightness/darkness variation, the opalescence parameter of zirconia was affected by yellowish/bluish color variation, and there was an inverse relationship between the translucency parameters of zirconia and contrast ratio [35]. 1.3 Types of Zirconia in Dentistry There are different types of zirconia ceramics available for dental application. They are grouped into five categories [7]: tetragonal zirconia polycrystals (3Y-TZP), partially stabilized zirconia (PSZ), zirconia toughed Alumina (ZTA) and graded zirconia. 1.3.1 Tetragonal Zirconia Polycrystals (TZP; e.g., Y-TZP, Ce-TZP) The first generation, tetragonal zirconia polycrystals (3Y-TZP), consists of 5.2 wt% or 3 mol% Y2O3 dopants and 0.25 wt% Al2O3 and has a small fine grain size (0.3-0.5 m), high fracture toughness (9-10 MPa.m1/2), high flexural strength (900-1200 MPa), and a Young’s modulus of 210 GPa at room temperature [36]. It is sintered at a relatively lower temperature compared to the second and third generations. The grain size is an essential determinant of the mechanical properties of 3Y-TZP. Studies have shown that above a critical grain size, the 3Y-TZP is less stable and more prone to t→m transformation. On the other hand, lowering the grain size below 1m is correlated with a lower transformation rate, to the point that transformation was not possible when the grain sizes were lower than ~0.2 m, which leads to reduced zirconia fracture toughness [41]. A crucial factor that affects the grain size and consequently strongly impacts the mechanical properties of zirconia material is sintering conditions (as will be discussed below in the sintering  12 section). Higher sintering temperatures and longer sintering time have been shown to increase the grain size [40, 42-44]. Some of the examples of the first generation 3-YTZP are DC Zirkon (DCS Precident, Schreuder & Co), Cercon (Dentsply Prosthetics), Lava (3M ESPE), and In-Ceram YZ (Vita Zahnfabrik). Recently, advanced protocols have been developed to reduce the opacity of zirconia and make it more translucent by intensifying the heat treatment conditions [36]. 1.3.2 Partially Stabilized Zirconia (PSZ; e.g., Ca-PSZ, Mg-PSZ, Y-PSZ) The second generation, partially stabilized zirconia (3Y-PSZ), consists of tetragonal precipitates in a cubic stabilized zirconia matrix. It is doped with 3 mol% of Y2O3, but the sintering aid (0.25 wt% Al2O3) is eliminated, and the sintering temperature and/or duration are increased. The grain size of 3Y-PSZ is increased to 0.5-0.7 m, and the cubic phase content is increased from 6-12% to 20-30%. As a consequence, the translucency parameter is increased to 24-31, and the biaxial strength is decreased to 900-1150 MPa [36]. An additional approach that can be used is to replace tetragonal zirconia grains with optically isotropic cubic zirconia particles. This can be done by increasing the yttria content to diminish the grain boundary light scattering to yield fully stabilized zirconia [39]. This generation of material has a larger grain size, which is associated with the presence of porosity and consequently wear. The cooling rate of this material has to be controlled due to the need for high sintering temperature (1680-1800C). A dental example of this material is Denzir-M (Dentronic AB), available for hard milling restorations.  The third generation, 4-5Y-PSZ, incorporates more optically isotropic cubic zirconia (50-80 %), has a grain size of 1-4 m and is produced by increasing the Y2O3 dopants to 4 to 5 mol% and increasing the sintering temperature and/or duration more than that of the second generation. Although esthetics are improved, cubic zirconia is weaker and more brittle than its tetragonal  13 counterpart. The translucency parameter is increased to 30-43, and the biaxial strength is decreased to 450-740 MPa, more in the range of lithium disilicate [45]. 1.3.3 Zirconia Toughened Alumina (ZTA) ZTA is a ceramic material that is based on zirconia combined with alumina matrix to advantageously utilize the stress-induced transformation capabilities of zirconia combined with the strength of alumina. A dental example of this group is In-ceram zirconia (Vita Zahnfabrik). Generally, In-ceram zirconia has lower mechanical properties than 3Y-TZP. However, the presence of Ce-TZP enhances thermal stability as well as the material resistance to LTD compared to 3Y-TZP under a similar aging process. In-ceram zirconia can be processed by either slip-casting or machining. The two processes result in similar microstructures. However, studies have found a significantly higher flexural strength for the slip-casting (630+-58 MPa) compared to machining (476+-50 MPa), but no significant difference was observed for fracture toughness [7]. 1.3.4 Graded Zirconia  There are polycrystalline materials in which glass is infiltrated into the surface of zirconia substrates to create a more damage-tolerant and esthetic system. It consists of gradual stiffness glass that gradually changes across the interface with resulting elastic modulus in the range of 125 GPa to 250 GPa [36].  1.4 Manufacturing of the Zirconia Prostheses 1.4.1 Soft Machining of Pre-sintered Blanks  Currently, the most popular route for fabricating zirconia prostheses is to use partially sintered zirconia blanks that are available in a partially sintered state. 3Y-TZP blanks are manufactured from zirconia powder that contains binder. The binder makes the blank suitable for pressing during manufacturing. This binder is eliminated during the pre-sintering in a carefully  14 controlled way (Figure 1-3). The blank is manufactured by cold isostatic press pressing followed by partial sintering to achieve a minimum strength required during blank milling. The mean pore size is between 20-30 nm, with a very narrow pore size distribution.    Figure 1-3 Cold isostatic pressing fabrication of partially sintered zirconia blanks [46].  The soft-milling technique makes zirconia blanks easy to mill in the CAM unit. However, after milling, zirconia prostheses must be fully sintered to achieve the final density and maximum strength of the material. This sintering procedure is accompanied by a high sintering shrinkage of approximately 20–30% [1]. In order to compensate for this shrinkage, the dimensions of the milled, partially sintered frameworks must be enlarged by an appropriate factor [2]. This factor varies according to the type of zirconia materials and microstructure. Companies indicate that factor to  15 the consumers in a form of barcode for each zirconia blank, which should be scanned and input to the CAM machine before milling the zirconia in the enlarged form.  1.4.2 Hard Machining of 3Y-TZP Fully sintered 3Y-TZP blocks are prepared by pre-sintering at a temperature below 1500C to reach a density of at least 95.5% of the theoretical density. The blocks are then processed to by hot isostatic pressure (HIP) at a temperature below 1400 and 1500 under high pressure in an inert gas atmosphere (Figure 1-4). This latter treatment leads to a very high density in excess of 99% of the theoretical density [19].   Figure 1-4 Hot isostatic pressure machining for fabrication of fully sintered zirconia [47].    16 Hard machining zirconia is a less common route of zirconia fabrication and it is referred to as a hard-milling technique using fully-sintered zirconia. Fully-sintered zirconia blanks can be milled to the actual size of the frameworks and no further sintering procedure, accompanied by subsequent sintering shrinkage, is necessary after milling, thus eliminating the somewhat uncontrolled shrinkage. Therefore, these frameworks showed good fitting accuracy in previous studies [48]. However, the high strength of such fully-sintered blanks does have the disadvantages of longer milling times and increased attrition of milling tools, which is undesirable for a production line in the laboratories. Additionally, fully-sintered zirconia requires a robust milling machine and a high temperature that will result in near surface damage and defect formation, which will significantly shorten the anticipated life span of the restoration. Therefore, milling in the “green” partially sintered state, followed by sintering, allows lower-temperature milling, and the sintering “heals” any milling-induced defects [49].  1.5 Sintering Zirconia  Sintering is defined as the process of transforming a powder into a solid body using heat. Traditionally, sintering is the principle method of processing ceramic bodies, but not unique to ceramics. Many of the techniques that are currently being used to shape and sinter ceramics have been used by potters for millennia but have been refined for today’s new ceramic materials. The zirconia sintering process involves several stages: densification, grain growth and then cooling. Sintering time and temperature (t/T), as well as the presence of impurities and stabilizer content, determine the grain size, amount of cubic phase, and stabilizer distribution. These, in turn, dictate the mechanical properties, metastability and resistance of zirconia to low-thermal degradation (LTD) [19].   17 The most common sintering method for zirconia is the use of conventional furnaces at temperatures between 1,350C and 1,600C and holding times ranging from 2-4 hours [50]. Conventional sintering furnaces include hot press (HP), hot isostatic pressure (HIP) and atmospheric furnaces. An alternative zirconia sintering protocol that is recommended by manufacturers using conventional ovens is a shorter, “speed” or fast sintering protocol that is claimed to save time and be more economical. Manufacturers’ “in-house” testing claims similar fit, translucency and color stability of zirconia restorations with either standard or fast protocols. Actual testing data to support the claims are, however, lacking. One in vitro study has recently shown that a combination of high sintering temperature with short sintering time increased the flexural strength of zirconia [51]. However, there are no reports documenting the effects of different sintering protocols on dimensional changes or distortion and its consequences in marginal fitting.  Several other alternative sintering methods for zirconia have been proposed in the literature, aiming to improve the mechanical and optical properties of zirconia, as well as ease of operation and control of sintering energy, and resulting in high productivity, safety and reliability. Among those alternative methods are spark plasma sintering [52], microwave [53], and vacuum furnaces [50].  1.6 The Clinical Studies of Zirconia-Based Crowns 1.6.1 Zirconia-based Crowns Because of its attractive properties, zirconia has gained traction in dentistry and has been increasingly used for the fabrication of coping material for all-ceramic crowns and fixed partial dentures [7, 8]. It has also been used in dental implantology as abutments or implants [10]. Clinical studies with short-term clinical data have shown that zirconia-based single crowns may serve as a  18 viable restoration [8, 11-13], but should not be considered as a primary treatment option [12]. According to Larsson and Wennerberg et al., life table analysis revealed cumulative 5-year survival rates of 95.9% for tooth-supported and 97.1% for implant-supported zirconia crowns [13]. Yet Sailer et al. reported an estimated survival rate of zirconia single crowns (with 95% confidence interval) to be closer to 92.1% [12].  Among technical problems associated with the clinical performance of zirconia crowns and fixed dental prostheses are those related to chipping and delamination of the veneering porcelain when applied on zirconia framework structures, and loss of retention. One of the main root causes of chipping/fracture of porcelain veneer problems is the dramatic differences in the coefficients of thermal expansion between zirconia and the veneering porcelain. In addition, incorrect anatomical designs of the crowns can put the weak porcelain at high stress bearing challenge with reduced likelihood of survival. Different modifications in the firing process and in the technical fabrication of fixed dental prostheses (FDPs) using zirconia as the framework have been attempted to address this problem [54, 55]. Limited data suggest the superior clinical outcomes of the pressed zirconia technique compared to conventional layering technique [11].  1.6.2 Full-Contoured Zirconia Crowns Zirconia has also been introduced as a full-anatomical contoured monolithic ceramic crown (FCZ) to be used without veneering porcelain to overcome the problem of mismatching materials that leads to chipping and/or dislodgement of the veneering porcelain. Currently, the use of monolithic zirconia is expanding into single- and multi-unit restorations, full-arch implant-supported prosthesis, abutments, implants, and orthodontic brackets.  FCZ crowns carry the advantage of a reduced tooth preparation since there is no need to create space for the framework and the veneering porcelain. Anecdotally, because zirconia is  19 regarded as a “very strong” material, preparations can be very conservative in tooth reduction since zirconia is expected to perform well in thicknesses of approximately 0.5-1.0 mm [56]. The most accepted finish line designs are round shoulder (RS) and chamfer finish line design. There is conflicting evidence about which design offers better marginal adaptation [57-60].  1.7 Post-Sintering Marginal Fit of Zirconia Crowns Esthetics, fracture resistance and adaptation are essential components in prosthetic crowns’ long-term success. Misfit of the crown prosthesis margin creates a potential space (marginal gap) between the restoration and the prepared tooth. Bacterial contamination can easily accumulate in the marginal gap and jeopardize the longevity of the treatment. Furthermore, adjustments of the prosthesis by grinding to achieve proper fit can create stress concentrations, which may reduce the resistance to fracturing of the crown and consequently lead to clinical failure [61].  1.7.1 Acceptable Marginal Gap A clinically acceptable marginal gap of dental prostheses has been debated in literature. The American Dental Association (ADA) specification No. 8 suggested that the luting cement film thickness for a dental crown should not exceed 25m when utilizing a type I luting agent and 40m when utilizing a type II luting agent [62]. While Christensen agreed with ADA specifications [63], Mclean and von Fraunhofer examined 1000 restorations’ marginal fits over a 5-year period and indicated that a marginal gap of less than 80 m is difficult to detect clinically. They also indicated that an acceptable marginal gap for full-coverage restorations after cementation should be less than 120m [64]. Fransson proposed a slightly higher marginal gap and that they should be less than 150m [65]. All of the previous studies measured the marginal gap of cast restorations.  On the other hand, there is inconclusive evidence regarding the optimum fit of contemporary ceramic systems despite the fact that this topic is heavily investigated. The reported  20 fit values for contemporary ceramic restorations in literature ranges between 7.5-206 m. Such a wide range of discrepancy between studies is attributed to the diversity in terms of methodology of the studies, ceramic processing technique as well as the lack of coherence regarding the definition of “fit” [62]. 1.7.2 Fit Terminology  Assessment of crown adaptation is described by the measurement of the marginal and internal gaps of crown restorations. According to Holmes et al. [66] (Table 1-2), the marginal gap could be vertical marginal discrepancy or horizontal marginal discrepancy. A vertical marginal discrepancy encompasses the distance between the restoration and the preparation when measured parallel to the long axis of the abutment, while a horizontal marginal discrepancy is the perpendicular distance from the internal surface of the restoration to the finish line of the preparation (Figure 1-5). The internal gap is the perpendicular distance from the internal surface of the restoration to the axial wall of the preparation [66].  Overextended margin is the perpendicular distance from the marginal gap to the crown margin, while the under-extended margin is the perpendicular distance from the marginal gap to the cavo-surface angle of the tooth. Absolute marginal discrepancy is defined by the angular combination on MG and the extension error (over-extension or under-extension), which represents the distance from the preparation finish line to the restoration margin. It is considered the best alternative measurement since it reflects the total crown misfit (vertically and horizontally) [66].      21 Table 1-2 Fit Terminology according to Holmes et al. [78] Term Definition A vertical marginal discrepancy encompasses the distance between the restoration and the preparation when measured parallel to the long axis of the abutment A horizontal marginal discrepancy the perpendicular distance from the internal surface of the restoration to the finish line of the preparation The internal gap the perpendicular distance from the internal surface of the restoration to the axial wall of the preparation Overextended margin the perpendicular distance from the marginal gap to the crown margin Underextended margin the perpendicular distance from the marginal gap to the cavo-surface angle of the tooth. Absolute marginal discrepancy is defined by the angular combination on MG and the extension error (over-extension or under-extension), which represents the distance from the preparation finish line to the restoration margin.   22  Figure 1-5: Fit definitions according to Holmes et al. [66].  1.7.3 Marginal Gap and Secondary Caries  Secondary caries (recurrent caries) can be defined as the carious lesion occurring associated with existing restorations [67], and it involves two parts, an outer lesion and a wall lesion [68]. The occurrence of an outer lesion is due to the deposits of plaque at the restoration margins. The occurrence of the wall lesion is proposed to be linked to microleakage at the tooth-restoration interface and to be dependent on the size of the marginal gap, but this is not supported by either clinical studies or laboratory models. On the other hand, larger marginal gaps have been found to have a significant effect on the development of secondary caries in vitro on indirect restorations [68]. Although positive correlation has been found between the marginal gap size and the development of secondary caries [69], no conclusive evidence exists to relate marginal gap  23 size and/or placement of the margin (supra/subgingival) to secondary caries. Moreover, studies were not able to find an association between marginal gap and microleakage [70, 71].  1.8 Gap in Knowledge In contemporary dentistry, the use of computer-aided design/computer-aided manufacturing (CAD/CAM) is becoming increasingly popular in the fabrication of dental prostheses [72]. It is recognized that every step of the fabrication process of zirconia ceramics must be carefully controlled [73]. One of the problems with CAD/CAM materials is that there is typically a discrepancy between the virtual model and the final structure. This discrepancy results from difficult-to-predict distortions of the prosthesis material across the various processing steps. Although discrepancies are always found [64, 74], no efforts have been made to investigate the sources and magnitude of such discrepancies in relation to the prosthesis processing and sintering and how they could be minimized. It has been recognized that processing of zirconia results in distortions of the structure due to sintering [31]. However, this information was obtained from very simple laboratory models that do not incorporate the typical 3D design and complex combination of thicknesses and shapes that are usually encountered when designing a real crown for dental prostheses. Therefore, the model currently available is very limited in helping to understand the dimensional alterations that occur with complex shape structures of CAD/CAM processed zirconia, and thus is of limited application for dentistry and other complex structures produced in a similar way.  The sintering shrinkage of the partially sintered zirconia is usually estimated as a single value and manufacturers do not provide information on how they were calculated for each specific batch of material. Additionally, it is not clear whether the estimated shrinkage percentage is based on linear or volumetric changes. Considering the three-dimensional shape of crowns and variances  24 in thickness, curvatures and finish line shapes, it becomes difficult to predict how accurately zirconia prostheses can be milled from the original virtual design using CAD/CAM technology.  While a certain degree of misfit is expected when trying a crown on the original preparation, such inaccuracy is taken for granted and little research has been dedicated to understanding the causes of the distortions during the processing of the crowns in order to minimize it. Inadequate fitting of crowns is usually dealt with by accepting a larger cement space and/or by making post-sintering bur adjustments to the crown to compensate for discrepancies, a procedure that can trigger t→m phase transformation with potential disastrous consequences for the prosthesis. Ideally, sintered zirconia crowns should present dimensions that match the original virtual design to perfectly fit to the original preparation with no adjustments to be made. Since dimensional changes are unavoidable during the processing of zirconia, it is important to understand how different thicknesses and shapes of margins could affect localized dimensional changes during sintering, and how that would affect the fitting of the crown. This could help better estimate the dimensional changes of zirconia during processing and propose preparation and crown designs that result in less distortion of the material, with consequent better fit.   Finite elemental analysis (FEA) has been used to investigate and potentially predict the internal stresses that may occur when processing zirconia. However, the method cannot determine the dimensional changes that occur due to internal stresses or any other causes. In addition, FEA has a very limited ability to provide information about the causes of distortions and suggest measures to prevent them. One of the concerns is that most of the reported properties of zirconia for dental applications have been obtained from testing specimens that are much thicker than the suggested thickness of currently used monolithic zirconia crowns. This is even more relevant to the margins, since some authors are now recommending a mini-chamfer shape [75] that resembles  25 a feather edge, with thickness far reduced from the traditional round shoulder or deep chamfer. Such thin margins for zirconia are being recommended without existing supporting evidence that zirconia can be processed under such conditions without compromised properties or behavior. There is currently a lack of comprehensive studies that evaluate the mechanisms involved, and the outcomes of the sintering process of zirconia, and how potential distortions may affect the adaptation of the crowns to the original preparation. To address this gap in knowledge, we investigated the effects of different finish line widths, occlusal thicknesses and different sintering protocols on dimensional distortions of zirconia by directly measuring the dimension difference between the virtual, milled and sintered copings and indirectly determining the accuracy of marginal fitting of monolithic zirconia crowns. We speculate on the causes of distortions in zirconia and propose a combination of design and sintering protocol that should result in minimal distortion and improved fitting of zirconia crowns. 1.9 Specific Aims and Rationales  1.9.1 Specific Aim 1 To review the influence of altering the sintering parameters used for dental zirconia processing, including changes in the sintering time, temperature (t/T) or methods used (furnace or technique) on the microstructure, optical and mechanical properties of zirconia. 1.9.1.1 Rationale for Aim 1 While methods for processing zirconia are well known, there is a tendency to modify the process parameters with the aim of decreasing the overall processing time and, in particular, the sintering time. There is lack of review in dental literature focusing on the influence of altering sintering parameters on zirconia properties.   26 1.9.2 Specific Aim 2 To systematically review the dental literature related to zirconia crowns’ and/or copings’ marginal and internal fit and to map all the factors that influenced the fit of zirconia crowns and/or copings. 1.9.2.1 Rationale for Aim 2 To assess what others have investigated in relation to zirconia crown marginal fit and dimensional changes and identify gaps in the knowledge.  1.9.3 Specific Aim 3 To investigate the influence of different finish line widths (0.5; 1.0; 1.2 mm) and crown thicknesses (0.8 and 1.5 mm) on the marginal fit of monolithic zirconia crowns using the manufacturer recommended standard sintering protocol.  1.9.3.1 Rationale for Aim 3 Zirconia prosthesis distortion during sintering is usually analyzed at the final stage, when adapting the prosthesis to the original scanned preparation. There is a lack of consistent evidence regarding the effects of different preparation designs on the marginal fit of monolithic zirconia crowns [58-60, 75]. Little is known about the fit of zirconia at thin thicknesses and whether the cutting and sintering processes of CAD/CAM designed prostheses can affect the thin-shaped design. If distortions increase with decreased thickness, then a minimal thickness to prevent significant distortions can be estimated and clinical recommendations made to improve the fitting and subsequent success rates of monolithic zirconia crowns.  1.9.3.2 Null hypothesis for Aim 3 There will be no significant differences in the marginal fit, regardless of the combination of crown thickness and finish line.  27 1.9.4 Specific Aim 4 To compare the effects of different sintering protocols (standard and fast) on the marginal fit of monolithic zirconia crowns.  1.9.4.1 Rationale for Aim 4 Zirconia manufacturers are recommending a short sintering protocol that saves time and is more economical. There is no evidence to support that using the fast sintering protocol results in equivalent marginal fit compared to the standard sintering protocol.  1.9.4.2 Null hypothesis for Aim 4 There will be no significant differences in the marginal fitting of zirconia crowns, regardless of the sintering protocol.  1.9.5 Specific Aim 5 To compare the effects of standard and fast sintering protocols on the dimensional changes among the virtually designed, the milled and the final sintered zirconia copings.  1.9.5.1 Rationale for Aim 5 Although there are some reported investigations on the effect of sintering methods on the physical properties of monolithic zirconia crowns [52, 53, 76], there is currently a lack of studies that evaluate the actual dimensional changes of zirconia crowns during the three processing stages (design, milling and sintering) and if the percentage of enlargement calculated for milling is equivalent to the percentage of shrinking during sintering, particularly when different sintering protocols are used.  There are no reported data of the assessment of dimensional changes of monolithic zirconia coping throughout the fabrication process and the comparison between the effects of different sintering protocols on dimensional changes. To address this gap in knowledge, we investigated the  28 effects of different preparation designs and sintering protocols on determining the accuracy of linear and volumetric dimensional changes occurring through the three separate steps of zirconia processing.  1.9.5.2 Null hypothesis for Aim 5 There were no significant differences in the volumetric and linear dimensional changes of zirconia copings, regardless of the combination of coping thickness, finish line offset and sintering protocols.      29 Chapter 2: The Influence of Altering Sintering Protocols on the Optical and Mechanical Properties of Zirconia: A Review  2.1 Purpose This review is focused on the influence of alterations in the sintering parameters used for dental zirconia, including changes in the sintering time, temperature (t/T) or methods used (furnace or technique) on the microstructure, mechanical and optical properties of zirconia and to provide clinicians with scientific evidence of the effects of changing sintering parameters used for dental zirconia on the microstructure, phase transformation, mechanical and optical properties of zirconia. 2.2 Materials and Methods 2.2.1 Search Strategy The search strategy was determined according to the well-established PICO strategy of 2009 [77] and involved the use of an electronic search of Embase (via OVID) and Medline (via OVID) using Boolean operators to locate relevant articles. The keywords were combined using “OR,” then joined using “AND.” The Medline search used the following combination of MeSH terms and keywords: (Monolithic OR Full-contoured OR Zirconia OR Zirconium OR Yttrium tetragonal zirconia polycrystalline YTZP) AND (Crown* OR Coping* OR Framework* OR Fixed Dental Prosthesis OR Full-arch Prosthesis) AND (Microstructure OR Mechanical Properties OR Flexural strength OR Optical properties OR Fracture toughness OR phase transformation OR Wear OR Low thermal degradation OR Thermal properties OR Translucency) AND (Sinter* OR Sintering OR Sintering time OR Sintering temperature OR  30 Sintering Protocol OR Sintering method OR Sintering Technique OR Speed sintering OR Fast sintering OR Furnace OR Oven OR microwave OR Firing). 2.2.2 Inclusion/Exclusion Criteria Inclusion criteria were used to find in vivo and in vitro studies published during and prior to June 2018 in the English language in peer-reviewed journals that contained all or part of the keywords in their headings. The included articles were focused on the assessment of the microstructure, phase transformation, and mechanical and optical properties of monolithic zirconia prostheses resulting from changes to the sintering protocol (t/Temperatures) and/or sintering methods. Studies that did not compare two or more sintering protocols or methods were excluded. Additionally, any studies that compared different sintering protocols but were not applicable to dental applications were excluded. The electronic search was accompanied by a manual search of issues published during the last three years by the following journals: Journal of Prosthodontics, Journal of Prosthetic Dentistry, International Journal of Prosthodontics, Dental Materials, International Journal of Periodontics and Restorative Dentistry, Journal of Oral Rehabilitation and Quintessence International. Additionally, the references in the selected articles were reviewed for possible inclusion. The titles and abstracts of all articles were reviewed by two independent reviewers and upon identification of an abstract for possible inclusion, the full text of the article was reviewed and matched against the predefined inclusion/exclusion criteria. 2.2.3 Extracted Data The author name and year of publication, the aim of the study, the type of zirconia used (brand name), the sample or prosthesis shape and dimensions, the sintering protocol (t/T), the sintering method, and the outcome were extracted from each of the selected articles.  31 2.3 Results The electronic search found 584 articles in Medline and 231 articles in Embase; after duplication removal and exclusion of review articles and studies in languages other than English, 198 studies remained. The titles/abstracts of the 198 studies were checked by two independent reviewers, which yielded only 13 studies that were processed for full-text review based on analysis of the abstracts. Manual searches of the references of the matched articles did not provide any further articles; therefore, only articles from the electronic search were chosen.  Excluded articles that did not meet the inclusion criteria were reviews, not in the English language, not in peer-reviewed journals, or that did not test and compare different sintering parameters or methods of zirconia sintering and their effects on the microstructure, phase composition, mechanical, and optical properties of zirconia. Two studies were excluded because of their irrelevance to the field of dentistry [78, 79]. Thus, 11 articles were ultimately selected for this review. After reading and analyzing the full texts of the 11 studies, the following factors were studied in terms of their effects on the alteration of sintering of monolithic zirconia: 1. Microstructure (grain size) [40, 42-44] 2. Mechanical properties [40, 42, 43, 53, 76, 80, 81] 3. Optical properties [42, 80-85] 4. Wear behavior [81] 5. Low thermal degradation (aging) [44] The data extracted from the reviewed articles are summarized in Table 2-1. Review studies have shown that altering the sintering time and temperature (t/T), as well as the presence of impurities and stabilizer content, primarily determined the grain size and microstructure of the zirconia materials [40, 42, 44, 76, 81, 82]. These, in turn, dictated the mechanical properties and  32 optical properties, including translucency, metastability and resistance of zirconia to LTD [42, 44, 81, 83]. Different methods that have been used to sinter zirconia include the use of conventional furnaces [40, 42, 44, 76, 81, 82], spark plasma sintering [78], microwaves [53, 83, 84] and vacuum furnaces [80].  Table 2-1 Summary of the 11 included articles (see Appendix A) Author Purpose Outcome Kim et al.[83] Effects of using different sintering techniques and various Zr thicknesses on “Optical Properties” Square specimens 22  22 mm There were statistically significant differences between conventional and microwave sintering methods and thicknesses (0.5, 1.0, 1.5 mm) on TP (F (2, 264) = 34.257,  < .001) and the color coordinates CIE L* (F (2, 264) = 17.198,  < .001)  and CIE a* (F (2, 264) = 20.724,  < .001), but not CIE b* (F (2, 264) = 0.989,  = .373) Kaizer et al.[81] Effects of speed sintering on optical, mechanical, and wear characterization In-Coris monolithic molar crown Increasing the sintering temperature and decreasing the sintering time yielded smaller grain sizes and higher translucency. S and SS groups exhibited a greater number of surface pits, which were associated with a greater volume and depth loss of the antagonist compared to that of the LT group.  33 Author Purpose Outcome Sulaiman et al.[85] Effects of staining & vacuum sintering on the optical and mechanical properties of PSZ & FSZ Disc zirconia samples  For TP value, FSZ were significantly higher than PSZ (p <0.05) regardless of the staining or the type of sintering used.  For CR values, from least to most translucent, PSZ stained < PSZ stain < PSZ vacuum < FSZ stained < FSZ vacuum < FSZ stain. For surface gloss value, staining increased the surface gloss of FSZ (p<0.05), but had no significant effect on PSZ. Type of sintering had no effect on either of the Zr types. For F.S value, PSZ had higher F.S values than FSZ (p <0.05). Staining increased F.S of FSZ, but the type of sintering had no effect. Neither staining nor the type of sintering had an effect of the F.S value of PSZ. Ersoy et al.[43] The effects of sintering t/T on the F.S of Zr (Bar specimen 1.2425 mm, 3YTZP) In-Coris ZI & In-Coris TZI  The mean F.S of Superspeed ZI group was significantly higher than Standard ZI and Speed ZI groups.  The mean F.S of Superspeed TZI group was significantly higher than Standard TZI and Speed TZI groups.  A combination of a high sintering temperature with a short sintering time increased the flexural strength of zirconia.  34 Author Purpose Outcome Ebeid et al.[42] Effects of changing sintering parameters on color, translucency, flexural strength Disc 15 mm in diameter Bruxzir 3Y-TZP Increasing the sintering temperature and time for Zr did not cause any statistically significant differences with regard to hardness or flexural strength, but significantly decreased the color difference (∆E; 4.4-2.2), contrast ratio (CR; 0.75-0.68) and roughness (Ra).  Inokoshi et al.[44] Effects of sintering conditions on LTD In-CeramYZ Higher sintering temperatures and times increased Zr G.S, led to decreased yttrium content in the remaining tetragonal grains and made the samples having a higher monoclinic phase more susceptible to LTD. Kim et al.[84] Effects of sintering time on density, G.S and translucency (light transmittance) 10101 mm Lava frame zirconia Kavo Everest ZS-blanks The density of Lava did not significantly differ from that of KaVo, and no significant difference in density according to sintering conditions.  Significant interaction was found between sintering conditions and Zr brand.  The longer the sintering time, the larger Zr G.S. Stawarczyk et al.[40] The effects of different sintering temperatures on F.S, CR, and G.S Ceramill ZI 3Y-TZP G.S increased as the sintering temperature was increased above 1300C, with the greatest G.S occurring at 1700C. The sintering temperature showed a significant negative correlation with F.S and the CR (p<0.001).  35 Author Purpose Outcome Almazdi et al.[53] Comparison of surface quality, mechanical & physical properties between furnace and microwave methods (YTZP Emax ZirCAD) Mean F.S C 1080.08 (79.37) and MS 1108.33 (162.55) Density C 99.9 (0.22), MS 99.9 (0.16) Porosity size was smaller in MS MS had uniform G.S. distribution Jiang et al.[82] Effects of sintering temperature and particle size on Zr translucency YPSZ discs The sintering temperature and G.S had a significant effect on light transmission (P<0.001) and increasing sintering temperature from 1350 to 1500C increased density and translucency (light transmission). Hjerppe et al.[76] Effects of sintering time on F.S ICE Zirkon Disc There was no statistically significant difference on F.S between thermocycled (Tc-20000) and non-thermocycled (Dry) Zr discs.  Zr, zirconia; PSZ, partially sintered zirconia; FSZ, fully sintered zirconia; CIELab (L* a* b*), color coordinates; TP, translucency; F.S, flexural strength; YTZP, yttria-stabilized tetragonal zirconia polycrystalline; MS, microwave; C, conventional furnace; CR, contrast ration; LT, long term; S, speed; SS, superspeed; ∆E, color difference; Ra, roughness, G.S., grain size (); t/T, sintering time/Temperature; h, hour (s); Tc, thermocycling; T, temperature  2.4 Discussion The studies included in this review have demonstrated that altering the sintering parameters used for dental zirconia has an effect on zirconia grain size, phase transformation,  36 and mechanical properties and optical properties, including translucency, metastability and resistance of zirconia to low thermal degradation [42, 44, 81, 83]. 2.4.1 Effect of Altering Sintering Time/Temperature on the Optical Properties of Zirconia The esthetic characteristics of a zirconia restoration are related to its optical properties, which include translucency, contrast ratio, color, direct transmittance of light, and opalescence. As previously discussed, different methods have been attempted to increase the translucency of zirconia. The elimination of light-scattering alumina sintering aids porosity and improves translucency but also requires a higher sintering temperature (1530°C) in conjunction with a longer dwell time (6 h), as in second generation zirconia. These changes, in turn, decrease the hydrothermal aging resistance of zirconia [86]. Another method of improving translucency involves increasing the Y2O3 content and sintering temperature and/or sintering duration [36].  The translucency of zirconia is additionally influenced by the ceramic brand and thickness [80], ceramic shade, primary grain size, refractive index, atmospheric conditions while sintering, surface roughness, contrast ratio, acidic medium, and staining [87], whereas the contrast ratio is affected by the zirconia brand and thickness, grain size, sintering temperature and duration, and translucency [80]. Color is affected by the number of firings, ceramic brand, ceramic thickness, cement color, cement thickness, abutment color, sintering temperature and duration, and number of coloring liquid applications [87]. Opalescence is affected by the number of coloring liquid applications and the ZrO2 and Y2O3 concentrations used (Table 1-1). A recent study investigated the optical characterization of In-Coris TZI Sirona monolithic translucent molar zirconia crowns produced using three sintering protocols: a long term protocol (LT) conducted at 1510C for 4 hours, a speed (S) protocol conducted at 1510C for 60 min and a  37 super-speed (SS) protocol conducted at 1580C for 10 min [81]. The authors found that the use of different sintering protocols significantly affected the grain size, translucency, hardness, and wear behavior of the antagonist. Increasing the sintering temperature and decreasing the sintering time yielded smaller grain sizes and higher translucency. The SS group exhibited the highest translucency among the three groups. This study appears to be more clinically relevant, as monolithic zirconia crowns were used.  Another study examined the roughness of monolithic zirconia after sintering at 1460C, 1530C and 1600C using 1-, 2-, and 3-hour holding times [42]. They found significant decreases in the color difference (∆E; 4.4-2.2), contrast ratio (CR; 0.75-0.68) and roughness (Ra) as the sintering temperature was increased. A mean ∆E value less than 3.0 is considered clinically imperceptible, a value of 3-5 is clinically acceptable, and a value greater than 5 is considered clinically unacceptable. When the CR is 0, the zirconia is considered to be most transparent, while zirconia with a CR of 1 is considered the most opaque. According to this study, all three different sintering parameters yielded clinically acceptable results, and increases in temperature allowed the zirconia to gain more translucency but still appear opaque [42]. This result could be attributed to the fact that increasing the sintering temperature reduced porosity, increased the density and consequently produced less light scattering and more light transmission. Another study used 3 mol% Y-TZP (second generation zirconia) discs/cylinders with two different initial zirconia particle sizes (40 vs. 90 nm) and four sintering temperatures (1350C, 1400C, 1450C, 1500C) [82] and found that the sintering temperature and grain size had a significant effect on light transmission (P<0.001) and increasing sintering temperature from 1350 to 1500C increased density and translucency. Therefore, it is clear that increasing the sintering temperature and decreasing the sintering time yields better translucency in sintered dental zirconia  38 ceramics. It has been documented in the literature that as the aging time is increased, the transparency decreases and the ceramic material becomes more opaque (higher contrast ratio), darker, reddish and yellowish [87]. It is also well known that aging zirconia roughens its surface by increasing the growth of the transforming monoclinic phase and the corresponding surface relief [87]. The sintering zirconia using microwaves is poorly addressed in the existing dental literature. A few studies have tried to evaluate the effects of using microwave sintering parameters on the optical properties of zirconia and to compare this method to conventional sintering techniques, but no clear conclusion has emerged from these comparisons [53, 83, 84]. Kim et al. [84] compared the optical properties of three different thicknesses of monolithic zirconia that were sintered using a conventional oven for 2 hours and a microwave oven for 30 min at 1500C and found that there were statistically significant differences in the effects of the different sintering methods and thicknesses on the color coordinates CIE L* and CIE a*, but not CIE b*; the reduced processing time used during microwave processing yielded similar color perception and translucency as did the use of a conventional sintering technique [83]. However, the color difference (∆E00) between the shade tab A2 and each subgroup was measured, and the average color difference was between 7.20 and 10.32 units, which is considered clinically unacceptable based on previous studies [88, 89]. Scanning electron microscope analysis found that a slightly smaller grain size range (100-250 nm) resulted from the conventional sintering than from the microwave sintering (250 nm) [53]. AFM analysis yielded a Ra value of 0.054 m for conventional sintering and 0.034 m for microwave sintering. The uniform pack appearance in the microwave samples could be attributed to better specular reflection and a higher color value compared to that resulting from conventional sintering. A higher monoclinic phase content resulted from both  39 sintering methods, and different amounts were found for different thicknesses.  Almazdi et al. [53] found that using microwave sintering yielded zirconia with reduced porosity and a uniform grain size distribution. On the other hand, Kim et al. [84] focused on evaluating the translucency of two commercial zirconia brands (Lava and Kavo) and found that despite the fact that there were no significant differences in density resulting from different sintering conditions, decreasing the sintering time resulted in smaller grain size and consequently increased the translucency; these results suggest that the interaction between the sintering method used and zirconia thickness has a significant effect on translucency [83]. 2.4.2 Effect of Altering Sintering Time/Temperature on the Mechanical Properties of Zirconia Reviewing zirconia literature, it has been observed that different zirconia types have different microstructures, particle sizes, porosity, size distribution, additive types and concentrations, and different raw material compositions. In addition, the microstructures within a single blank can be heterogeneous. From a mechanical perspective, one study found that significantly increasing the sintering temperature and time for zirconia material (Bruxzir 3Y-TZP) did not cause any statistically significant differences with regard to hardness or flexural strength, although it significantly enhanced translucency and color reproduction [42]. Another study showed that the grain size of 3Y-TZP zirconia increased as the sintering temperature was increased above 1300C, with the greatest grain size occurring at 1700C, and that the sintering temperature showed a significant negative correlation with flexural strength and the contrast ratio (p<0.001) [40]. In contrast, another study showed that a combination of a high sintering temperature with a short sintering time increased the flexural strength of zirconia [43], but no further analysis of the  40 results was provided. Therefore, the results so far are inconclusive in regard to the relationship between increased sintering temperature and flexural strength. The effect of full zirconia restorations on the wear of antagonistic teeth is an issue of great clinical significance [20]. The wear behavior of any material is a complex phenomenon and can be affected by many factors, including patient-related factors such as dietary habits, dysfunctional occlusion, masticatory forces and bruxism, as well as material type, fracture toughness, internal pores, surface flaws and/or defects in the microstructure, physical properties and surface texture (finishing and polishing of the restoration surface) and environmental factors [20]. Kaizer et al. [81] studied the effects of speed sintering (LT, S and SS; as mentioned above) on the wear behavior of monolithic zirconia crowns. The authors found that areas of mild and severe wear were observed on the zirconia surface in all groups. However, micropits in wear craters were less frequent in the LT group, while the S and SS groups exhibited a greater number of surface pits, which were associated with a greater volume and depth loss of the antagonist compared to that of the LT group. The authors also found that the t→m phase composition was related to the wear crater; this, in turn, raised concerns regarding the adjustment of occlusion when delivering monolithic zirconia prostheses, especially in cases where speed and superspeed sintering protocols and chair-side technologies have been utilized. Although it appears that speed sintering yielded poorer wear behavior than long-term sintering, more studies are needed to produce a conclusive statement. In addition to finding that increasing aging time decreased transparency [87], Burgess et al.[23] also found that aging zirconia for 5 hours in a dental autoclave at 135C and 2 bar pressure increased its roughness, but not by a statistically significant amount; no increase in opposing enamel wear was noted. Additionally, SEM analysis showed that it had a similar surface smoothness as non-aged zirconia. It should be noted that this was an in vitro study; therefore,  41 application of the results to clinical situations should be cautioned against. Inokoshi et al. [44] found that higher sintering temperatures and longer sintering times increased zirconia grain size, which led to decreased yttrium content in the remaining tetragonal grains and a higher monoclinic phase content; such materials are more susceptible to the effects of aging. Sintering in a vacuum furnace appears to improve the flexural strength of zirconia. However, vacuum sintering also significantly enhances the translucency of partially sintered zirconia and has no significant effects on fully sintered zirconia [80].  Because there are many approaches used to determine translucency in the dental literature [90]—the contrast ratio , transmission coefficient and translucency parameter (TP)—caution has to be taken when comparing translucency between studies without establishing uniform critical factors. The major factors affecting translucency include specimen thickness, the reflectance parameters of the black and white backings, and optical contact [91, 92]. Therefore, comparison at established thickness, backing and optical contacts are recommended.  2.5 Conclusions Alteration of sintering parameters has been found to alter the microstructural, mechanical and optical properties of zirconia. Increasing the sintering temperature and decreasing the sintering time improves light transmission and decreases the contrast ratio, and therefore enhances the optical properties of zirconia. The reviewed results were, however, contradictory regarding the effects of changes in sintering time and temperature on the flexural strength of zirconia. While alteration of the sintering parameters and methods would be expected to alter the wear behavior of monolithic zirconia and its effect on antagonistic surfaces, more studies are needed to confirm these effects. It is crucial for dental professionals, including both clinicians and technicians, to be  42 aware of the source of zirconia materials and processing techniques and the related mechanical and optical properties, as well as proper handling.  In summary, increasing the sintering temperature and decreasing the sintering time improved the translucency of zirconia in in vitro studies but also had negative effects on its mechanical behavior. Therefore, one would expect that the clinical performance of monolithic zirconia restorations would be influenced by alterations in the methods and/or parameters used for sintering. Finally, there is a lack of comprehensive clinical studies regarding the influence of altering sintering parameters or fabrication methods on the performance of monolithic zirconia restorations, and further investigation in the future is encouraged.  43 Chapter 3: Fit of Tooth-supported Zirconia Single Crowns - A Systematic Review of the Literature  3.1 Purpose The purpose of this study is to systematically review zirconia crowns and/or coping studies related to marginal and internal fit and to map all the factors that influenced the fit of zirconia crowns and/or copings. 3.2 Materials and Methods 3.2.1 Search Strategy The focused question was determined according to the well-established PICO strategy of 2009 [77]: 1) Population: crown or coping prostheses fabricated in vitro; 2) Intervention: zirconium oxide material; 3) Comparison: N/A; 4) Outcome: factors affecting marginal and internal adaptation. The focused question of the presented review was “Within the available in vitro studies on full coverage crown or coping prosthesis, what are the factors affecting the marginal and internal adaptation of zirconium oxide crowns and/or copings?” The search strategy involved conducting an electronic search through Embase and Medline (OVID) using Boolean operators to locate appropriate articles as described in Tables 3-1 and 3-2. Systematic reviews and non-English articles were excluded from the search. The electronic search was supplemented by manual searching for the last 8 years through the following journals: Dental Materials, Journal of Oral Rehabilitation, Journal of Prosthetic Dentistry, Journal of Prosthodontics, International Journal of Prosthodontics, International Journal of Periodontics and Restorative Dentistry, and Quintessence International. In addition, the references of the selected articles were reviewed for possible inclusion.   44 Table 3-1 Search strategy in MEDLINE applied for this review Search Literature search strategy  Papers found Population Crown* OR Coping* OR exp Crowns/ 92,757 Intervention Zirconia OR Zirconium OR Ytrium-stabilized tetragonal zirconia YTZP 3,392 Control N/A N/A Outcome Marginal fit OR marginal adaptation OR internal fit OR internal adaptation OR accuracy OR discrepancy 844,947 Total 1 AND 2 AND 3 AND 4 731 Exclusion  Dental Implants/ or Dental Prosthesis, Implant-Supported/ 577 Limit Limit it to English language and reviews  532  Table 3-2 Search strategy in Embase applied for this review Search Literature search strategy  Papers found Population Crown* OR Coping* OR exp Crowns/ 134,744 Intervention Zirconia OR Zirconium OR Ytrium-stabilized tetragonal zirconia YTZP 15,542 Control N/A N/A Outcome Marginal fit OR marginal adaptation OR internal fit OR internal adaptation OR accuracy OR discrepancy 1,996,919 Total 1 AND 2 AND 3 AND 4 316 Exclusion  Dental Implants/ or Dental Prosthesis, Implant-Supported/ 297 Limit Limit it to English language  297   45 3.2.2 Inclusion/Exclusion Criteria  The search inclusion criteria were studies published from December 1, 2009 until September 1, 2019 and limited to in vitro studies published in peer-reviewed journals, articles written in English which contained all or part of the key words in their headings, and articles assessing marginal adaptation and/or internal adaptation and/or accuracy on single crowns for tooth-supported restorations. The search was restricted by excluding “implant-supported prostheses” and review articles. Therefore, the search generated 382 articles to be reviewed initially by reading titles and abstracts after duplication removal. 3.2.3 Selection Criteria  The titles and abstracts of all articles were reviewed by two independent reviewers (author and co-author). Disagreements between the two reviewers were resolved by discussion. Upon identification of an abstract for possible inclusion, the full text of the article was reviewed and cross-matched against the predefined inclusion criteria. Figure 3-1 illustrates the process of identifying the included articles in the review as a flow diagram. Table 3-3 describes the reasons for excluded studies.    46  Figure 3-1 PRISMA flow diagram to identify the included studies in the review   Potential relevant studies according to initial search (n=1047) Studies to be evaluated by title/abstract (n = 382) Limiting the search by English language, No implant-supported crowns, No reviews Full-text articles assessed for eligibility (n = 46) Inclusion criteria: In vitro studies, tooth-supported zirconia crowns, fit assessment Studies included in qualitative synthesis (n = 46) Studies included in quantitative synthesis (meta-analysis) (n = 0) Records identified through MIDLINE (OVID) database (n=731) Records identified through EMBASE (OVID) database (n=316) Studies excluded after title/abstract (n= 336) Studies excluded after full-text reading (n= 0) Removing the duplicates  47 Table 3-3 A descriptive table for excluded articles  Reason for Exclusion   Results  Implant, implant-supported restoration, implant abutment  34 Fracture and fatigue testing  65 Bonding tests  25 Different design, fixed partial denture (bridge), inlay, onlay, post and core 38 Microleakage and thermocycling testing  14 Other all-ceramic materials  22 Surface treatment of zirconia   6 Clinical studied and case reports  57 Reviews  30 Finite element analysis and stress distribution studies  15 Optical properties, translucency, color 10 Non-relevant studies  14 Wear studies  3 Chipping studies  3  3.2.4 Data Extraction The following data were extracted from each selected full-text article: type of fabrication system, factor tested influenced the fit, sample size, type of finish line/preparation design, cement thickness, measurement method, measurement number, and marginal and internal gap measurements. Any variable that could not be extracted was scored as not reported (“nr”).   48 3.2.5 Quality Assessment The inter-observer calibration was evaluated by Cohen’s Kappa and the chosen cut point was 80%. GRADE Criteria were used for quality assessment of the selected studies [93]. The quality levels were High (H), Moderate (M), Low (L) and Very Low (VL). Quality reflects our confidence that the estimate of the effect is correct.  3.3 Search Results The electronic search collectively revealed 1047 articles, 731 from search strategy from Medline and 316 from search strategy in Embase, of which, after duplication removal, 382 studies were processed for review according to the analysis of titles and abstracts. Searching manually and through the references of the selected articles did not provide any further articles; therefore, only the articles from the electronic search were considered. The articles that did not meet the inclusion criteria were in vivo studies, fixed dental prostheses of two or more units, implant-supported prostheses, testing other types of all ceramic restorations not zirconia, not in English language, not in a peer-reviewed journal, or testing bond strength or accuracy of scanning. Thus, 46 articles were selected for quality assessment of marginal and internal fit of zirconia crowns. Most of them had moderate or low-quality assessment, with a Kappa score of 0.8. 3.3.1 Factors Affecting Zirconia Marginal Fit  After reading and analyzing the full texts of the 46 in vitro studies, the factors that were studied and showed influence on the fit of zirconia crowns were the following: • Using different manufacturing systems (14), using different zirconia materials (13) • Comparing between digital and conventional impression techniques (6) • Effect of cementation (7)  49 • Effects of different finish line configurations (4), depth or curvature (2), width (1), and cement space (1), and changing the occlusal preparation (1) • Effect of veneering (5), using different veneering techniques (1) • Influence of using different die materials with or without powder (1) • Altering sintering protocols (2) 3.3.2 Methods Used for Measuring Marginal and Internal Fit of Zirconia Crowns The methods that were used for assessing the marginal and internal fit of zirconia crowns were the following: • Direct view technique (20) • Sectioning after cementation (10) • Replica technique (12), digitalized replica technique (1) • Triple scan optical protocol (2) • Micro-computed tomography (micro-CT) (1) • 3D coordinate measuring system (CNC Rapid) (1) • Weight technique (1) Assessing measuring points varied between studies even within each measuring technique, as shown in the summary table of included articles (Table 3-4). The same applied to the cement space selection. Due to the high heterogeneity of the methodologies between the selected studies, it was impossible to draw any conclusion on the best methodology to evaluate the fitting accuracy of zirconia crowns. 3.3.3 Description of the Selected Studies  A summary of the articles included for final analysis is described in Table 3-4. Table 3-4 Summary of the articles included for final analysis 50 Study  Factors Materials/System  S.S Preparation Design Measure  Zr/Sinter Results G Ahmed et al.[94] Sintering effect  Different finish lines and crown thickness   Atlantis core file abutment fabrication   10 3 finish line 0.5, 1.0, 1.2 mm 2 crown thickness 0.8, 1.5 mm 12° taper Vertical marginal gap Stereomicroscope ×40 then ImageJ software  IPS e.max ZirCAD  2 sintering protocols Standard 1450C for 9 hours 50 min and fast 1520C for 2 hours 50 min   1.0-mm finish line in both crown thicknesses showed the lowest VMG H Mejia et al.[95] Different preparation taper   Resin maxillary left central incisor  Digital impression then print out the resin die  10 -8, -4, 0, 8, 12, 16, 22° tapers 50 μm cement space Silicone replica technique  Kavo dental GmbH semi-sintered zirconia   -8° showed the highest marginal gap 58.2 μm and 22o  showed the least marginal gap 42.1 μm M Khaledi et al.[96] Sintering time  Coping  Digital impression after scan spray  3D laser scanner (3ShapeD810; 3Shape, Copenhagen, Denmark) 10 7 mm high, 1 mm wide, 6° occlusal convergence angle, 90° shoulder finish line  0.5 mm coping thickness Digital microscope  18 measurements  1 hour, 15 minutes for IPS e.max ZirCAD, 4 hours 20 minutes for Speed ZrO2, 7 hours 20 minutes for the conventional ZrO2 IPS e.max 41 μm Speed ZrO2 43 μm  conventional 39 μm M Dahl et al.[97] Dual scan technique to measure the gap Digital scanner Trios  3 No details  Digitalized replica  24 marginal measurements/group No sintering details  Pre-sintered Zr Fully sintered Zr Milled CoCr Laser sintered CoCr L Pilo et al.[98] Cementation effect Cementation type Conventional impression then Lava scanner  10 0.4-mm chamfer finish line 6° taper, 50 μm cement thickness Stereomicroscope ×50 20 measuring locations Absolute marginal gaps Sectioning Lava frame blocks No sintering details Pre-cementation 35 μm, Post-cementation 72 μm  M Boitelle et al.[99] Method of measurements Compare 2D vs. 3D (Coping) Conventional impression  30 Upper molar and premolar  Replica by silicone by light microscope vs Triple scan by digital 3D map  No sintering details  Triple-scan method was more reliable than silicone replica  M Yus et al.[100] Impression technique Scanning silicone impression and scanning stone  30 Upper left molar Cr-Co SEM ×600 12 points  Zirconium dioxide Scanning silicone 22 μm Scanning stone 8.94  μm M  51 Schriwer et al.[101] Zirconia type  Soft milling vs. hard milling  10 Upper premolar  0.5-mm chamfer finish line  9-12 o Replica BruxZir 1530C Zirkonzahn1450-1555  Prettau 1600 C NobelProcera N/A Denzir Y-TZP Denzir AB 1800 C Internal fit (IF) occlusal is larger and significant than axial I.F H Ortega et al.[102] Zirconia type Procera, Lava, In-ceram YZ, MC 10 Steel spacemen Cement thickness 50 μm  SEM Measure external (EMG) and internal marginal gap (IMG), Sectioning after cementation 3 zirconia groups and one MC group Nobel Procera is the lowest (EMG=39 μm and IMG=41 μm)  MC (EMG=83 μm and IMG=101 μm)  M Kocaagaoglu et al.[103] Digital vs conventional impression   Acrylic Max Premolar → coping Die type: Stone Convention impression (cn) then scanning → In Eos X5 Scanner.  CEREC (Omnicam; Sirona)→ group C (InLab SW 15.0; Sirona Dental Systems). 3Shape Trios-3 → group Tr (DWOS; Dental Wings).  10 Anatomic occlusal reduction 2 mm, 4-6° taper, axial reduction 1-1.5 mm, chamfer 1.0 mm, 0.5 mm above the CEJ,  0.5-mm copings with 30 m cement space starting 1 mm from the margins Replica 50N then measured by stereomicroscopy ×50 21 measurements per coping: 8 for marginal, 8 for axial, 5 for occlusal gaps→ 210 points (ICE Zircon Translucent; Zirkonzahn SRL)  Sintered at 1500 C for 2 hours with approximately 8 C/min heating and cooling rate   MG: 85.6 m for Cn, 58.7 m for C, and 47.7 m for Tr.  AF: 85.4 m for Cn, 76.1 m for C, and 66.7 m for Tr. OF: 177.3 m for Cn, 177.9 m for C, and 135.2 m for Tr. H Dahl et al.[104] Digital vs conventional impression   Human mand 1st molar → Crowns Trios scanner 18  No details  Triple scan protocol   (Zir; Dental Direkt) No sintering details  (HIP-Zir; Denzir)  Zir 78 m HIP 81 m Li 76 m M-Co-Cr 90 m L-Co-Cr 82 m Cast-Co-Cr 58 m L Pedroche et al.[105] Digital vs conventional impression   (Coping) -Intraoral scanning (direct) -Scanning of PVS (indirect) - Scanning of the gypsum cast/models (indirect) 10 Supragingival circumferential chamfer finish line, 2.0-mm occlusal reduction, 1.5-mm axial reduction, axial convergence angle of 6° and rounded angles Replica  16 measurements  Total 160  (Metoxit, Thayngen, Switzerland)   MG Gypsum 87 m PVS 71 m Scanner 59.2 m M  52 Kale et al.[106] Effect of cement Space on MG   Ivorine right maxillary first molar  D9003Shape 5 0.5-mm axial reduction, chamfer finish line. Cement space 25 m at the margins and at 1 mm above the finish lines was set at 30 m for group 25-30, 40 m for group 25-40, and 50 m for group 25-50  a stereoscopic zoom microscope 8 sites /crown A total of 120 measurements in the 3 groups StarCeram Z-Nature; H.C. Starck)   mean MG was  85 m for group 25-30 68 m for group 25-40 53 m for group 25-50  M Ha and Cho[107] 2 CAD/CAM systems X Veneering effect  Monolithic crowns Vs pressed veneered Zr copying  Mand 1st molar acrylic  Zirkonzhan vs. Ceramill 10 1-mm chamfer  2-mm occlusal reduction 5 convergence angle Weight technique + Replica (figure pressure) then  Leica microscope 5 points per replica Total 50  Zirkonzhan: sintered at 1600°C for 10 hours in a ZIRKONOFEN 600 furnace  Ceramill: sintered at 1450°C for 11 hours in a Ceramill Therm furnace  MG: Ceramill was between 106 and 117 μm, and the Zirkonzahn system was between 111 and 115 μm.  I.F: Ceramill was between 101 and 131 μm, and Zirkonzahn was between 116 and 131 μm H Dauti et al.[108] Digital Vs conventional  After cementation  Left mand 1st molar   Lava C.O.S 20 0.8–1.2-mm chamfer F.L., 1.5-mm occlusal reduction, 6° convergence angle set to 0.01-mm thickness to a level of 1 mm above the margin and the cement space was set to 0.04 mm.  Cementation under constant finger pressure for 10–15 min,  292 measurements Half with stereomicroscope and half with SEM  Sectioning Zenostar Zr Translucent blank  a Cercon® heat plus furnace (DeguDent GmbH, Germany) for 8 h at 1350 °C   MG: Lava Optical 96.283 μm, Conve optical 94.845 μm Lava SEM 99.265 μm, Conve SEM 83.376 μm AMG: Lava Optical 191.543 μm, Conv optical 158.609 μm Lava SEM 211.600 μm, Conve SEM 152.721 μm M Boitelle et al.[109] Different CAD/CAM systems (copings) acrylic model (a right max 1st molar (Cerec inLab system group)  (Dental Wings/ Wieland Zenotec mini system group)  (Dental Wings/Wieland Zenotec T1 system group)  20 A 1.5-mm a chamfer finish line, A 2-mm occlusal reduction For C, 20-μm margin 70-μm A and occ 3D triple-scan optical technique  more than 5604 measurements   Pre-sintered Zr MG: C 54.32 μm, Zm 66.56 μm, ZT 61.08 μm AF: C 115.76 μm, Zm 100.01 μm, ZT 76.94 μm L  53 and a left max 1st premolar) For Zm, Zt, 20-μm margin 70-μm A and 100-μm occ OF: C 143.82 μm, Zm 124.06 μm, ZT 127.41 μm Vojdani et al.[59] Shoulder Vs Chamfer X Firing porcelain effect   (Copings) Brass master dies  Conventional impression than scanned with a laser scanner (3Shape D810; 3Shape, Copenhagen K, Denmark)  10 A 1-mm chamfer and shoulder F.L., 6 occlusal convergence and a height of 7 mm. Anti-rotational ledge. The copings were designed with a thickness of 0.5 mm considering the 30 μm spacer 1 mm short of margin.  (AMG) was taken at 18 points by use of a digital microscope and photographed sequentially at 230X.    (VITA In-ceram YZ-14; Vident, Germany)  Chamfer coping 49.87  Chamfer Crown 68.24 Shoulder coping 35.20 Shoulder crown 63.06 L Torabi et al.[110] Different veneering techniques (layering (L), press-over (P), and CAD-on (C) techniques). Copings.  A brass master die  Conventional impression than scanned with 3D-laser scanner (3ShapeD810; 3Shape, Copenhagen K, Denmark)  10 7-mm height, 6 degrees of occlusal convergence and a 90 shoulder of a 1-mm-wide finish line. An antirotational design in the axial surface.  (VMG) Images from the 18 points using a digital microscope connected to PC and photographed at 230X.  (IPS e.max ZirCAD, Ivoclar Vivadent)  Layering 63.06 Press-over 50.64 CAD-on 51.50  M Pimenta et al.[111] Different Materials Copings Model of left maxillary canine (acrylic resin) Marginal (MG) and internal fit (IF)  - Zirconia YTZP (ZirkonZahn) *Sintering for 7 hrs at 1600C in Fire HTC Sirona - Lithium Disilicate LSZ(IPS e.max Press system) 850C - Nickel-chromium NiCr alloy (Lost-wax casting) 400-800C 5 Model of left maxillary canine (acrylic resin) Taper 6, 2-mm incisal reduction, 1.2-mm facial reduction, rounded angles, 120 chamfer finish line→ scanned and Zr master model was reproduced → 15 stone die Micro-CT, Skyscan 1173, 130 KV, 61 A, 1-mm-thick AL filter, a pixel size 9.91 m, scanning time 90 min/specimen.  Adobe Photoshop CTAn SkyScan software  M.G 4 points I.F 9 points  Zirconia YTZP (ZirkonZahn) *Sintering for 7 hrs at 1600C inFire HTC Sirona  M.G.: YTZP 35.5 m LSZ 76.19 m NiCr 34.05 m I.F: YTZP 86.95 m LSZ 73.36 m NiCr 117.88 m M Ortega et al.[112] 3 CAD/CAM vs MCC maxillary first premolar  Metal-ceramic Lava Procera Vita in-ceram YZ 10 1-mm-wide circumferential chamfer finish line and axial walls tapered at 6 degrees.  All crowned were cemented with GI and sectioned BL applying a load of 10 N for 10 min then SEM 1) metal-ceramic, (2) NobelProcera Zirconia, (3) Lava Zirconia, and (4) VITA In-Ceram YZ.  MG: MCC 101.5 m Lava 49.48 m Procera 41.09 m YZ 65.63 m L  54   Nakamura et al.[113] -Frame (coping) -Crown (Zr-veneer) -Marginal, internal fit and fracture resistance Hybrid Zr (fully sintered before milling) Dense Zr Commercial Zr Sintering 1450 C for 2 hr 7 Jacket crown epoxy→ scanned → milled to Titanium abutment. Maxillary 1st molar Lingual collar for support  Heavy chamfer 0.8 mm Replica (9.6N) M.G: 40 points per specimen (microscope). I.F: Fitting test material  Hybrid Zr  Dense Zr Commercial Zr Sintering 1450 C for 2 hr M.G.:  Frames: 48.9-58.2 m  Crowns: 48.6-59.4 m I.F: Frames: 125.6-139.5 m Crowns: 128.2-138.2 m M Lins et al.[114] 3 fabrication systems  24 Zr copings Prefabricated Titanium Abutments  Ceramill Lava 3M Neoshape Using 3 different laboratories  YTZP 0.6 mm thickness 8 Cementation by using Zn phosphate cement  50 N UTM Cement thickness after cementation, Zn phosphate then sectioning BL+ MD. Optical microscope X100, X200 6 locations  Y-TZP  -Internal misfit were 72.1, 69.4, 76.4 m -Marginal discrepancy 40.9, 34.2, 39.3 m -Absolute marginal discrepancy 65.8, 70, 74.5 m M Ji et al.[58] 2 CAD/CAM systems  Chamfer vs shoulder finish lines  Maxillary 1st premolar  Prettau Zirconia Zenostar ZR translucent Lithium disilicate IPS e.max press (control)  16  12 occlusal convergence angle, 1.5-mm occlusal reduction, a 1-mm shoulder (S) or deep chamfer (C)margin. Crowns were bonded to stone dies with (Rely X Unicem). light microscope equipped with a digital camera (Leica DFC295) magnified by a factor of 100 Sectioning Prettau Zirconia Zenostar ZR translucent  Prettau MG S 119 m ZR MG S 92 m Li MG S 41 m Prettau MG C 109 m ZR MG C 85 m Li MG C 41 m Prettau AMG S 74 m ZR AMG S -14 m Li AMG S 29 m Prettau AMG C 38 m ZR AMG C -52 m M  55 Li AMG C 23 m Alghazzawi et al.[115] Different die  150 monolithic zirconia crowns Mandibular 1st molar melamine tooth.  Argen FZC Polyurethane master die 4 dies (3 stones and 1 Ti) 3shape scanner D9000  10  1-mm rounded shoulder OG 4 mm 12 total convergence 1.5-mm occlusal reduction  Die spacer 35 m Replica technique  8 measurements  Steromicroscope X40 Argen (monolithic zirconia crown)   MG 49.32 to 91.20 mm.   M Sener et al.[116] Cementation effect (type of cement) Correlation to microleakage. Forty freshly extracted human first maxillary premolars  Correlation to microleakage  10 1-mm chamfer finish lines, 1.5-mm occlusal reductions, 6 degrees of occlusal convergence Replica → optical microscope at (100X) (Leica). While 10 crowns were luted with MDP-RC (Panavia) F 2.0, the other 10 were luted with GCI (Vivaglass) under a weight of 50 N for 10 minutes  Cercon system using a Cercon Brain unit (DeguDent GmbH)   the Precident DCS System (DCS Dental AG)   Cercon (85 ± 11.4 μm)  DC-Zircon (75.3 ± 13.2 μm)  The mean cement thicknesses of GIC (81.7 ± 13.9 μm) and MDP-RC (78.5 ± 12.5 μm)  VL Re et al.[117] The effect of finish-line configuration on Zirconia coping  2 maxillary artificial teeth Lava All-ceramic system (3M ESPE) Lava Frame Zirconia Blanks, 3M ESPE Lava Furnace 200, 3M ESPE 10  Axial reduction: 1-1.5 mm Occlusal reduction: 1.5-2 mm round shoulder or chamfer Width 0.8 mm 100X optical microscope  50 measurements   Lava Frame Zirconia VMG: Shoulder 30.2+-3 μm Chamfer 28.4+-4 μm L Miura et al.[118] Different finish line widths  Veneering effect Non anatomical crown   Not mentioned  15 shoulder widths of 6, 8, and 1 mm    Replica  Cement thickness 30 micron  9 points measurement per sample No sig diff between before and after firing  S 27 μm, RS0.2 30 μm, RS0.5 24 μm   L Habib et al.[119] Different occlusal preparation Zirconia Copings  Extracted premolar  CAD4DENT CAD/CAM 3D Digital Scanner (7Series from Dental Wings Inc. Montreal, Canada).  15 (anatomical 30, semi-anatomical 15-30, and non-anatomical 0), 2-mm occlusal reduction, 1-mm chamfer finish line, 1-mm axial Copings were adjusted, cemented and sectioned BL 9 measurements    Did not mention which Zirconia type Overall mean gap values: 155.93+/-33.98 μm  Anatomical design had the best fit 139.23+/-30.85 μm M  56 reduction, 5-10 angle of convergence, Cement space 0.01 mm Euan et al.[57] 2 CAD/CAM systems X 2 finish lines   Zr. Copings extracted molar teeth Lava all-ceramic system and Lava Chairside Oral Scanner 10 Round shoulder (1 mm 90) vs Chamfer (1 mm 45) 2-mm occlusal reduction, 6 axial convergence, 1-1.5-mm axial reduction. Steromicroscope coupled with digital camera.  20 measurements  Zirconia material and sintering protocol were not mentioned  C Lava all-ceramic 64.07  C Lava oral 18.46 S Lava all-ceramic 52.67 S Lava oral 14.99 M An et al.[120] Digital vs conventional  Zr copings. base-metal dies from 1 maxillary central incisor
 (iTrios)  10 2.0-mm incisal reduction, 1-mm axial reduction, 1.0-mm chamfer margin of 1.0 mm, 6 degrees of convergence. A die spacer was applied to the stone dies of the CI group (60 mm) & simulated die spacers were set for the iP group and iNo group (60 mm), starting 1.0 mm from the margin Replica + a light microscope at 50 magnification  4 location  Zirblank; Acucera  No sintering details  Conven better than digital  CI group: 92.67 (13.94) mm; iP group, 103.05 (14.67) mm; and iNo group, 103.55 (16.50) mm.  L Yildiz et al.[121] Two zirconia type  Crowns (Zr copings + veneering) Measurement before cementation  20 Chamfer Fl. was 1 mm above the CEJ; preparation margins were not beveled.  Core 0.5-mm thickness Replicas using a light microscope (Leica at ×200). 40 measurements/specimen. 1,600 measurements for both zirconia systems  IPS ZirCAD zirconium oxide blocks (IZC)  Lava zirconium oxide blocks (L)  MG was 89.26 μm for L crowns and 88.84 μm for IZC crowns,  L crowns showed significantly larger axial and occlusal gaps than IZC crowns  L  57 Seelbach et al.[122] Simplified molar crown Accessible marginal inaccuracy  IF: Internal fit Lava, cerec, iTero 1 step and 2 steps PVS impression  10  Circular chamfer  I.F. by 3D- coordinate at 50 points/crown. VMG. by traveling microscope & digital micrometer IPS Empress CAD, Ivoclar Vivadent, milled on CEREC Inlab I.F. 49+/- 25 m AMG 44+/- 26 m M Sakrana[123] 3 different zirconia materials Cementation effect  Mandibular first premolar   in-ceram zirconia  Zirkonzhan Composite blocks   10 1-mm shoulder  2-mm occlusal reduction 6 taper  4-mm axial height  Steromicroscope  Before and after cementation  C-gem self-adhesive cement  12 measurements/ crown. 360 before and 360 after sectioning No sintering details Before cementation  In-ceram 56.3 m Zirkonzhan 60.16 m composite 56.16 m After cementation  In-ceram 84.2 m Zirkozan 84.22 µm composite 95.22 m L Regish et al.[124] Zr Vs NiCr copings X veneering effect Standardized metal master die prepared anterior crown   Ceramill (Amann Girrbach, Germany) Sintering for 8 hours GI cement 5Kg  5  Chamfer finish line  Triangular shaped orientation notch on the base Cement thickness after sectioning with SEM.  Ceramill therm furnace for 8 hours NiCr was better than Zr but both deteriorated after veneering L Hamza et al.[125] 2 Fabrication systems X different materials Crowns  Stainless steel dies mandibular second molar Cerc inLab vs. Kavo everst Zirconia vs. Lithium disilicate 10  10.00-mm cervical diameter, 6.00-mm height, 6 total occlusal convergence. The occlusal surface was prepared with 2 sloping surfaces (one slightly beveled). Round shoulder 1.0 mm F.L.  Binocular Microscope at X100 8 predetermined measuring locations  No sintering details  VMG: Zr: 14-86 m Li disilicate: 28-40 m Lowest mean M.G. was Zr manufactured by Everest 14 m +-5.2 M Asavapanumas and 3 Different finish line curvature X 3 diff materials 3 Diff finish line curvature 1, 3, 5 mm 3 diff materials cercon, IPS emax, Lava  12 A 1.2-mm shoulder margin, 2-mm incisal reduction, 1.5-mm labial and axial reduction, and A stereomicroscope  4 sites  Cercon 0.4 IPS emax 0.6 (pressed) Lava 0.4 5 mm G (Cercon, 76.59 μm; IPS e.max, 106.44 μm; Lava, 128.34 μm) M  58 Leevailoj[126] ivorine maxillary central incisor  then casted into cast in cobalt chromium molybdenum   using a polyether impression material  a total occlusal convergence of 6 degrees  0.4 mm on a 30-μm die spacer    than for both the 3-mm G (Cercon, 60.18 μm; IPS e.max, 81.79 μm; Lava, 99.19 μm) &1-mm G (Cercon, 38.3 μm; IPS e.max, 52.22 μm; Lava, 69.99 μm)  Rinke et al.[127] 2 different CAD/CAM upper left second premolar acrylic tooth model   absolute marginal discrepancy (AMD)   Digitized with the Cercon eye (EYE) scanner (DeguDent, Hanau, Germany), while the other 20 specimens per parameter were digitized using the 3Shape D-700 scanner (3S) (DeguDent, Hanau, Germany).  10 A 1.0-mm, 360° rounded shoulder. The occlusal reduction was at least 1.5 mm, and the resulting convergence angle was set at 2×2° (4-degree taper).  Cement space 60 μm  Light microscope  Twenty-four measurement points,  staggered by 15°,   Sintering for these specimens was done for 6 h at 1,350°C (Cercon heat, DeguDent, Hanau, Germany).  Maximum MG ranged from 112.24±23.1 μm (EYE/COMP) to 144.6±30.5 μm (EYE/EXPERT). Average MG ranged from 57.9±6.49 μm (EYE/COMP) to 71.0±10.8 μm (3S/COMP).  M Euan et al.[60] Extracted molar  two different finish line configurations before and after porcelain firing cycles, after a glaze cycle, and after cementation   Extracted molar  LavaTM system, Veneer IPS e.max Ceram, Cementation with RelyXTM Unicem, AplicapTM  10 Chamfer vs. Shoulder Finish line  cementation  Measurements for MG using stereomicroscopy (40×) were performed at four stages: copings (S1), after porcelain firing cycles (S2), after glazing (S3), and after cementation (S4) No sintering details  Shoulder  S1: 50.13 μm S2: 54.32 μm S3: 55.12 S4: 59.83 Chamfer S1: 63.56 S2: 71.85 S3: 74.12 S4: 76.97 M Chandrashekar et al.[128] Maxillary central incisor  Zr copings Compare between Zr Vs NiCr marginal fit  Cercon for Zr→ cement space 30 μm 1 mm away from the margin. Sintering 1350C for 6.5 hr. 0.5 mm thickness Lost wax technique for NiCr 15  Machined steel die 8 mm height 7 mm cervical dimeter  6 taper 1-mm shoulder finish line 90 SEM X50 ImageJ software  1350 C for 6.5 hours  M.G Zr 39.32 μm M.G. NiCr 129.98 μm VL  59 measurement mid b, mid L, mid M, mid D Moldovan et al.[129] Copings Internal fit accuracy,  cercon (dry-mill) Vita in-ceram (wet-mill)  CAD/CAM wet and dry Zr Copings  2 types of silicon 20 Rounded shoulder  Made by reverse engineering    3D Replica method (replica of cement space) by optical digitalization and computer-assisted analysis 20000 to 35000 per die According to Cercon® Heat, Degudent GmbH, Hanau, Germany and Zyrkomat®, Vita Zahnfabrik, Bad Säckingen, Germany Root means square  Molars 28.6 (0.7) m Premolars 24.9 (0.5) m M Martinez-Rus et al.[130] Four Different manufacturing system  Ceramic copings Extracted mandibular first premolar  AMD without cementation  In-Ceram YZ (Cerec inLab system)  A conventional waxing technique digitized by Cercon, and  Procera Zirconia (Nobel Biocare AB  40 resin dies  10 A 1.2-mm deep chamfer 2-mm occlusal reduction  Taper 6   A stereomicroscope X40 40 measuring points  Marginal gap discrepancy  IZ N/A IY 1530 C for 8 hours CC 1350 C for 6 hours PZ 1540 C  IZ: 29.98 m (3.97) IY: 12.24 m (3.08) CC: 13.15 m (3.01) PZ: 8.67 m (3.96) M Korkut et al.[131] Cementation and aging  human premolars extracted  cementation with (Variolink II, Ivoclar- Vivadent).  (Procera All-Zircon, Cercon Smart Ceramics) in contrast to heat-pressed ones (Empress 2).   10 1-mm chamfer preparations 1 mm above the cemento- enamel junction.  2-mm occlusal reduction 6° convergence angle was targeted to be 6°  Cementation, then aging, then thermocycling. Stereomicroscope at 17 sites using a computer-aided stereomicroscope at 100× magnification Sectioning  No sintering details  CAD/CAM (43.02 μm) Heat-pressed (47.51 μm)  L Grenade et al.[132] Copings  No veneering  Fabrication method  Procera and Ceramill 10 In vivo prep Cementation and sectioning  2 MG, 7 IG  Ceramill Therm according to manufacturer  Procera 51 Ceramill 81 M Azar et al.[133] Preparation depth 0, 1.5, 3 mm Right max canine C Left mand 1st Optical scanner (CEREC inLab, Sirona Dental Systems)   12 C0, C1.5, C3 P0, P1.5, P3 Cement space is 0 a light microscope   No sintering details  0→BL 47 μm & MD46 μm  1.5→BL58 μm & MD43 μm 3→BL64 μm & MD47 μm  M  60 SS, Sample size; Zr, zirconia; MG, marginal gap; AMG, absolute marginal gap; I.F, internal fit; SEM, scanning electron microscope; MCC, metal ceramic crowns; Li, lithium disilicate; CAD/CAM, computer-aided design, computer-aided manufacturing Pak et al.[61] Two fabrication system X Veneering extracted maxillary central incisor  Digident and Lava 20 2-3-mm incisal reduction, axial reduction of approximately 1 mm, a 1-mm shoulder margin, 6 tapered angles, an approximate height of 7 mm  A light microscope with image processing at 50 points that were randomly selected  Pre-sintered blanks Fully sintered blanks  Digident 61.52 μm before veneering and 83.15 μm after veneering.  Lava 62.22 μm before veneering and 82.03 μm after veneering  M Baig et al.[134] Diff materials X Diff finish line Crowns   YTZP, pressed Li disilicate and cast metal shoulders or chamfers  10 1-mm shoulder, 20° taper 1.5-mm occlusal reduction  4-mm axial height Stereomicroscope  6 measurement  No sintering details  CAD/CAM (66.4 μm) Heat-pressed (36.6 μm) Cast metal (37.1 μm) M 61  3.4 Discussion   The purpose of this systematic review was to map all the factors influencing the fit of zirconia crowns and/or copings and to update the latest review published in 2011 by Abduo et al. [28]. Reviewing the literature, it was found that it is difficult to compare the marginal and internal adaptations of zirconia crowns between studies because of the high variabilities in the methodologies, including using different fabrication systems and impression techniques, different materials and different cements, different die materials and methods for assessing the fit. Other factors include the effects of different preparation designs, porcelain veneering and multiple porcelain firing, and the effects of zirconia aging and thermocycling and their correlation to microleakage. Only two studies have examined the effects of sintering technique or changing the sintering protocol (altering the sintering rate t/T) on the adaptation and fit of zirconia crowns [94, 96]. Ahmed et al. [94] found a significant interaction between crown thickness, finish line width and sintering protocol on the marginal fit of zirconia crowns, yet Khaledi et al. [96] did not find significant differences between three different sintering times on adaptation of zirconia copings. However, none of the studies have investigated the effect of an ultrafast sintering protocol (chair-side) on the marginal adaptation of zirconia restoration.  Most of the studies scored “low-to-moderate” according to GRADE evaluation criteria. Evaluators were moderately confident in the effect estimate due to the high variabilities in the methodologies, missing many important details and/or the quality of the peer-reviewed journal. It was found that most of the studies were missing the sintering protocol details, including the t/T as well as the technique used for sintering.  Most of the studies investigated the effects of using different manufacturing systems or zirconia types for fabricating zirconia prostheses or compared between the digital and conventional 62  impression techniques using either direct technique or replica [101, 102, 104]. Other studies investigated the effects of veneering within different manufacturing systems. Ha and Cho [107] evaluated the fit accuracy of two zirconia systems (Ceramill and Zirkonzhan) and studied the effect of pressed veneering over zirconia copy and compared it to monolithic zirconia crowns. Theirs was the only study to use the weight technique to determine the overall fit accuracy by weighing the silicone impression of the cement space. In addition, they used the internal replica technique to assess the marginal and internal gaps. The Ceramill system was significantly higher than Zirkonzhan system, 20.02 m +/- 1.02 and 17.72 m +/- 1.05, respectively. The marginal gap was smaller with Ceramill and the internal gap was smaller with Zirkonzhan. The marginal and internal gaps were higher after pressing veneering compared to before veneering. In this study, they used the manufacturers’ instructions to design and fabricate the prostheses, which may be attributed to the differences in the weight techniques between the two systems. The Ceramill system recommends a 50-m cement space, while Zirkonzhan recommends 35 m. The differences between the marginal and internal gaps before and after veneering were explained by the fact that porcelains melt and gather to fill the pores during processing, resulting in contraction and compressive force that leads to marginal gap discrepancies. This is supported by a finite element analysis that claimed that a thicker cement space leads to a higher stress concentration in veneered zirconia crowns [135]. Lins et al. [114] compared the internal, marginal and absolute marginal discrepancies of 24 zirconia copies fabricated by 3 CAD/CAM systems, Ceramill, Lava, and Neoshape, on implant abutment Cone Morse (CM). The I.F and M.G. were assessed after cementation using zinc phosphate cement and sectioning MD and then BL. Regarding the mean value of internal fit, Ceramill was 72.1 m (4.05), Lava was 69.4 m (3.0) and Neoshape was 76.4 m (3.42). A 63  significant difference was found between Lava and Neoshape (P=.002), yet no significant differences were found between Ceramill and Neoshape or between Ceramill and Lava (P>.05). Regarding the mean value of the marginal gap, Ceramill was 40.9 m (8.44), Lava was 34.2 m (5.92), and Neoshape was 39.3 m (5.67). Therefore, no significant differences were found for marginal discrepancies between the Ceramill and Lava (P=.147), Ceramill and Neoshape (P=.878), or Lava and Neoshape (P=.321). For the absolute marginal discrepancy mean value, Ceramill was 65.8 m (7.62), Lava was 70.0 m (15.9), and Neoshape was 74.5 m (6.80). Thus, no significant differences were found between the Ceramill and Lava (P=.860), Ceramill and Neoshape (P=.534), or Lava and Neoshape (P=.842) systems. The fact that the fabrication of the copings was in three different laboratories according to the system used limits the trueness of extrapolating the results to reflect the clinical conditions.  The selected articles presented significant heterogeneity regarding the experimental procedures, which led to different discrepancies being measured and made it impossible to provide a strict ranking of the different systems in terms of accuracy or to perform a meta-analysis. The accuracy of data acquisition varied according to the system used and several optical impression technologies. In addition, the software used and the milling accuracy differed. However, the majority of crowns manufactured by the various ceramic systems satisfied the requirements for marginal adaptation. Marginal and internal adaptations of zirconia were staggered and varied among conventional and digital CAD/CAM ceramic systems. Multiple studies demonstrated a superior [103, 105], comparable [108], or inferior [104, 120] marginal fit of digital impressions compared to conventional impressions. Consideration should be given to the study design, methodological parameters, and measurement tools when comparing the results, keeping in mind that increasing 64  the processing steps in fabricating a restoration allows for the accumulation of errors. Therefore, one would accept that direct digitalization will yield better marginal and internal fit of the restoration. One could also expect deformation of the conventional impression material while removing the prepared tooth from the impression and during the casting procedures, in addition to the expansion and shrinkage of the materials used.  Few studies have been found to investigate the effect of cement or cementation on the marginal gap. One study measured the absolute marginal gap of crowns cemented by 4 types of cement and was not able to find a linear correlation between microleakage and absolute marginal discrepancy [136]. The second study is the only published study that focused on the effect of cement space on the marginal gap of monolithic zirconia crowns and found a significant relationship between them [106]. There was a significant improvement of marginal fit with the increase of cement space. Despite the fact that Cristian et al. [136] measured the absolute marginal discrepancy in zirconia crowns cemented by 4 different types of cements, it would be more beneficial to measure the marginal gaps before and after cementation to test the effect of cementation on the marginal gap. The filler content and consequently the viscosity and flow can affect the crown seating and therefore the marginal gap. In addition, the effect of the force applied during cementation on the marginal gap is also important information. One of the most influential factors for marginal adaptation of zirconia prostheses is the preparation design. Ahmed et al. [94] investigated the effects of different finish line widths (0.5, 1.0, 1.2 mm) and two crown thicknesses (0.8, 1.5 mm) under the influence of two sintering protocols and found that the preparation design has a major influence on the marginal fit and that the 1.0-mm finish line showed the lowest consistent results under both sintering protocols and for both crown thicknesses. Another published study investigated the effect of cement space on the 65  marginal gap. They found that increasing the cement space increases the observed fit and that group 25-50 (53 m) had the smallest gap compared to groups 25-40 (68 m) and 25-30 (85 m) [106]. This study should be interpreted with caution due to the low measurement points investigated.  Ji et al. [58] evaluated the marginal gap and absolute marginal discrepancy between chamfer and shoulder finish lines using 2 zirconia CAD/CAM systems (Prettau Zirconia and Zenostar ZR translucent) and compared the results to lithium disilicate IPS e.max press (control). The gap measurements were performed after cementation of the crowns with resin cement (Rely X Unicem) using a light microscope equipped with a digital camera (Leica DFC295) magnified by a factor of 100. They found that the fabrication system and the finish line configuration significantly influenced the absolute marginal discrepancy (P<.05) [58]. In addition, they found that lithium disilicate had smaller marginal and absolute gaps compared to zirconia. In contrast to most studies, they also found that the chamfer finish line yielded a better marginal adaptation compared to the shoulder finish line. Vojdani et al. [59] found that the marginal fit of shoulder copings was significantly better than that of chamfer copings, but there was no significant difference between the two margins after firing the porcelain. Euan et al. [57] studied the influence of using two fabrication systems (Lava all-ceramic system and Lava Chairside Oral Scanner) in regard to using two finish line designs (round shoulder and chamfer) and showed that zirconia restoration made with a chair-side intraoral scanner displayed a significantly better marginal fit compared to the one scanned, and the difference between chamfer and shoulder finish lines on the marginal gap was noticed only when using the intraoral scanner Lava all-ceramic system. Habib et al. [119] studied the effects of different occlusal surface preparations on marginal and internal fits of zirconia copings on extracted 66  premolars. The anatomical design (30) had the best fit compared to the semi-anatomical (15-30) or non-anatomical (0) designs. Euan et al. [60] measured marginal adaptation of zirconia crowns fabricated by CAD/CAM with the Lava TM system and prepared with two finish line designs and noted the effects of the porcelain firing cycles, glaze cycles, and cementation on the marginal misfit of crowns in both groups. They found that the round shoulder finish line is significantly lower than the chamfer finish line and that porcelain firing cycles and glaze cycles had significant increasing effects on the chamfer group due to the small amount of porcelain applied at the edge area that was easily altered during porcelain firing cycles and glaze firing cycles. However, cementation procedures had no influence on the marginal gap in both groups using figure pressure technique. Although quantitative assessments could be performed between chamfer and shoulder finish line studies, the authors are not confident with the results because of the variabilities in methodology between the studies.   Five studies considered evaluating the influence of veneering on the fit of zirconia restorations. Ha and Cho [107] compared two systems and determined the effect of porcelain press veneering. One study found a significant difference between the absolute marginal gaps of chamfer and shoulder finish-line groups before (49.87, 35.20 μm) and after (68.24, 63.06 μm) porcelain firing, respectively, and found that the absolute marginal fit of shoulder copings was significantly better than that of chamfer copings, but with no significant difference between the two margins after firing the porcelain [59]. The second investigated the effects of different veneering techniques (layering, press-on, or CAD-on) on the vertical marginal gap [110]. It showed a significant effect of the veneering technique on the vertical marginal gap and determined that there was an increase in the vertical MG after porcelain veneering that was highest in the layering technique (63.06 μm) 67  compared with the press-on (50.64 μm) and CAD-on (51.50 μm) techniques. The third study compared marginal gaps between nickel chromium and zirconia copings before and after veneering and found that nickel chromium had a better marginal fit, but both deteriorated after porcelain veneering [124]. The fourth study did not find an effect before and after veneering on the same system on the marginal accuracy [61]. However, the fifth study investigated the effect of multiple firing cycles on marginal fit and found no significant difference in terms of ceramic type, finish line design, margin location, and their interactions [137]. The investigated studies on veneering ceramic on zirconia frameworks showed a multifactorial effect. The difference noticed between the studies could be related to the technique of veneering, the margin design, the porcelain firing, the thickness, materials and design of the veneering layer and the zirconia framework. The veneering effect could be explained by the fact that porcelain veneering involves heating the ceramic until melting. When the porcelain particles melt, they gather to fill the voids and induce compression stress that leads to coping deformation around the circumference of the margin. In addition, the differences in mismatch between the veneering layer and the zirconia place the veneering ceramic under compression stresses, which, in turn, leads to margin distortion and consequently may deteriorate the fit. Generally, there was no conclusive evidence on the best methodology to evaluate the fitting accuracy of zirconia crowns. Most of the studies have assessed the marginal fit of zirconia prostheses with the direct view technique using external microscopes and the internal fit with either internal microscopes (sectioning after cementation) or the replica technique. Assessment of internal fit using microscopes is a destructive method that requires sectioning of the specimen. One of our selected studies evaluated the marginal and internal fits of zirconia crowns using micro-CT, while two studies used the triple scan technique, one used CNC-Rapid profilometry and one 68  used the weight technique. Therefore, direct comparisons between studies were not possible, as studies varied in their methods of measurements as well as other factors, such as die types, sample size and number of measurements per specimen, preparation and finish line design, and when the gap was measured (before or after cementation, before or after storage).  According to the previous studies, we can see that there is no consensus on how many measurements should be taken per specimen to obtain an accurate and clinically relevant conclusion on marginal and internal gaps. In addition, our findings highlighted the importance of obtaining individual measurements without combining the results, which complicates interpreting the results in terms of their clinical relevancy. Groten et al. [138] suggested that 50 measurements along the crown margin can provide clinically relevant information if the measurements were taken at equal distances or were randomly selected. In contrast, Gassino et al. [139] reported that the minimum number of measurements required to ensure clinical relevancy for gap measurements was 18. None of the studies evaluated the effect of aging on the marginal and internal adaptation of zirconia restoration. Few studies tried to evaluate the effects of sintering parameters on the mechanical properties of zirconia and to compare conventional sintering techniques [43, 53, 80, 84, 140], and two only investigated the effects of using different sintering protocols on marginal fitting [94, 96].  One of the limitations of this systematic review is that it relied on two databases for the identification of potentially eligible studies. Future studies may investigate the effect of other sintering protocols used for zirconia restorations and their impact on marginal adaptation. Studies with long term follow-up of the clinical performance of monolithic zirconia crowns are needed.   69  3.5 Conclusions  Generally, there was no consensus on the best methodology to evaluate the fitting accuracy of crowns. A variety of methods and testing parameters were used for this purpose, mainly including direct view, cross-sectional view, and impression replica techniques. Furthermore, direct comparisons between studies were not possible, as studies varied in their types; sample size and number of measurements per specimen; preparation and finish line design; time at which the gap was measured; whether the measurements were of cemented or non-cemented crowns; storage time and aging procedures after cementation; type of abutment used for measurements; type of microscope and enlargement factor used for measurements; and location and quantity of single measurements.  Within the limitation of this systematic review we can conclude the following: 1- Regarding the effect of preparation design on the marginal fit of zirconia crowns, shoulder finish lines had a slightly better marginal adaptation compared with chamfer finish lines. Crowns obtained from anatomical tooth preparation had better marginal and internal fit than semi-anatomical or non-anatomical designs. Furthermore, increasing the cement space significantly improved the fit of zirconia crowns.  2- Zirconia crowns obtained from digital impression techniques had comparable results to those of conventional impression techniques. Recent studies have showed the superiority of zirconia adaptation on crowns obtained from digital impressions.  3- Most of the studies reviewed investigated the fit of the 3 mol% yttria tetragonal polycrystalline zirconia materials (YTZP) (first- and second-generation zirconia), whereas few studies investigated the fit of the third-generation zirconia 4 and 5 mol% yttria partially stabilized zirconia. Meanwhile, many studies failed to specify the type of zirconia material 70  used in their study, and none of the reviewed studies investigated the fit of nano-structured zirconia materials. 4- Veneering porcelain on zirconia copings increased the marginal gap compared with that without veneering. Layering technique showed higher marginal gaps compared with press and CAD-on techniques.  5- Regardless of the type of cement use, cementation increased the marginal gap of zirconia crowns. Further studies should focus on the effect of cement thickness and load applied during cementation on the marginal adaptation of zirconia crowns.  6- Very limited data are available regarding the effects of fast sintering protocol (increased sintering temperature and decreased time) on the marginal gap of zirconia prostheses, and no data are available regarding the effect of an ultrafast (chair-side) sintering protocol, which is 30 min in duration, used to sinter the new chair-side zirconia materials on the marginal fit of zirconia prostheses.     71  Chapter 4: Influence of Crown Design and Sintering Protocol on Marginal Fit of Monolithic Zirconia Crowns   4.1 Purpose Considering the three-dimensional shape of crowns and variances in thickness, curvatures and finish line shapes, the crown might not undergo uniform shrinkage in all dimensions during sintering and that may affect the marginal fitting of full-contoured zirconia. There is a lack of consistent evidence regarding the effects of different preparation designs on marginal fit of FCZ [58, 60, 75, 141]. There are also no studies investigating the effects of different sintering protocols on marginal adaptation of monolithic zirconia crowns and no evidence to support that using a fast sintering protocol results in equivalent marginal fit compared to the standard sintering protocol. Accordingly, the purpose of this study was to investigate the influence of different chamfer finish line widths (0.5 mm, 1.0 mm, 1.2 mm) and crown thicknesses (0.8 mm and 1.5 mm) on the marginal fit of FCZ crowns fabricated by computer-aided design/computer-aided manufacturing (CAD/CAM) method using standard and fast sintering protocols. Therefore, specific aims 3 and 4 were combined in this project. The null hypothesis was that there is no significant influence of finish line width, crown thickness and sintering protocol on vertical marginal gaps of FCZ crowns. Materials and methods  4.1.1 Fabrication of the Master Dies Six digitally customized, machine milled, titanium implant-abutments were used to fabricate the master abutments for monolithic zirconia crowns. Atlantis abutments core files from Dentsply Sirona Implants were chosen because they eliminate the need to scan the titanium 72  abutments after the milling process. A scan body (FLO, Atlantis, Waltham) was placed on a mandibular model with an Astra implant on the location of the right permanent mandibular first molar. A dental laboratory scanner (3 Series scanner, Dental Wings, Canada) was used to scan the model and the scan body once and then, using the “later order feature,” to order the abutments. Dental Wing software was used to import the files and design the six master abutments individually. Emergence shape and width were set as a default. Marginal position and shape “45 Chamfer” were identical in all the abutments but with three different finish line widths, which are 0.5 mm, 1.0 mm, and 1.2 mm (Figure 4-1).    Figure 4-1 Illustrations showing the digital fabrication process of the core file abutment. A dental laboratory scanner was used to scan the model and Atlantis FLO to order the abutments (Left). Dental Wing software was used to import the core files and design the six master abutments individually (Right).  Two types of occlusal reductions were designed: three “short” abutments (5.0 mm) with a 1.5mm clearance from the opposing tooth, and three “tall” abutments (5.7 mm) with a 0.8 mm 73  clearance from the opposing tooth (Figure 4-2). Each finish line design was combined with either a short or a tall abutment. Abutment angulation had a total occlusal convergence angle of 12° in all the designs. All dies were designed to have semi-anatomical occlusal reduction. The master abutments were transferred to a manufacture milling unit (Atlantis Milling Centre, Waltham, Massachusetts, USA) that accepts open-format Stereolithography (STL) to be milled into titanium abutments.    Figure 4-2 Upper row: Photographs showing the titanium abutment (Left: tall abutment (5.7mm); right: short abutment (5.0mm). Lower row: Illustrations showing the relationship between the abutment length and crown thickness (Left: tall abutment and thin crown; right: short abutment and thick crown).  74  4.1.2 Crown Fabrication Crowns were designed virtually on “Dental System” software (version 18.1.0, 3Shape, Copenhagen, Denmark). Cement thickness was set at 0 m at the margin and 30 m, 1 mm above the margin and elsewhere. FCZ crowns were designed with the same outer dimensions occlusogingivally, mesiodistally, and buccolingually. Anatomical features and details were set as default with uniform thickness (Figure 4-3).     Figure 4-3 Digitally designed monolithic zirconia crown. Example showing the different parameters used to set the cement thickness marginally and internally (Left). Example showing the software interface for designing the different crown dimensions (Right).  Crowns were sent to a third-party 5-axis milling machine (Wield Select, Ivoclar Vivadent, Schaan, Liechtenstein) at the dental milling center to be milled. IPS e-max ZirCAD LT zirconia blanks (Ivoclar Vivadent, NY, USA) were used to mill twenty crowns per design by soft-milling technique. The milling machine software was programmed to account for the shrinkage percentage of the partially sintered zirconia blanks after sintering. Each blank possesses a specific barcode accounting for the post-sintering shrinkage. After milling the pre-sintered zirconia crowns, the 75  pieces were separated from the blanks using diamond burs and gently ground with fine-grain emery paper. 4.1.3 Experimental Groups From twelve test groups (n=10 per group), 6 groups were randomly selected for standard sintering (SS) and the other 6 were randomly selected for fast sintering (FS). Experimental groups in term of finish line widths, abutment length, crown thickness and sintering protocol are illustrated in Figure 4-4 and Table 4-1.  Table 4-1 Experimental groups according to the different combinations of finish line widths, abutment length, crown thickness and sintering protocol. Group Chamfer Finish line  Abutment Length  Crown thickness Sintering  G1 0.5 mm  5.7 mm-Tall 0.8 mm-Thin  SS G2 0.5 mm  5.0 mm-Short 1.5 mm-Thick  SS G3 1.0 mm  5.7 mm-Tall 0.8 mm-Thin SS G4 1.0 mm  5.0 mm-Short 1.5 mm-Thick SS G5 1.2 mm  5.7 mm-Tall 0.8 mm-Thin SS G6 1.2 mm  5.0 mm-Short 1.5 mm-Thick  SS G7 0.5 mm  5.7 mm-Tall 0.8 mm-Thin  FS G8 0.5 mm  5.0 mm-Short 1.5 mm-Thick  FS G9 1.0 mm  5.7 mm-Tall 0.8 mm-Thin  FS G10 1.0 mm  5.0 mm-Short 1.5 mm-Thick  FS G11 1.2 mm  5.7 mm-Tall 0.8 mm-Thin FS G12 1.2 mm  5.0 mm-Short 1.5 mm-Thick  FS SS: standard sintering; FS: fast sintering  76    Figure 4-4  Schematic diagram illustrating the different experimental groups. “Ti” refers to titanium abutments.  4.1.4 Sintering Protocol The “soft-mill” crowns were sintered according to the manufacturers’ recommended sintering protocols using the same conventional sintering furnace (Programat S1 Furnace, Ivoclar Vivadent, NY, USA). Enlarged crowns were positioned to allow for 20-25% linear shrinkage during sintering on the occlusal side. Crowns in G1 to G6 groups were sintered by SS protocol and the other crowns (G7 to G12) were sintered following a FS protocol (Figure 4-5).  6 Ti abutments3 Tall abutments(5.7 mm)Master die fabricationCrown fabricationSinteringAssessmentThin crowns0.8 mm120 crowns equallydivided among groups(n = 10)Standard sintering (SS)60 crownsVertical marginal gapassessmentFast sintering (FS)60 crownsThick crowns1.5 mmFinish line0.5 mmFinish line1.0 mmFinish line1.2 mmFinish line0.5 mmFinish line1.0 mmFinish line1.2 mm3 Short abutments(5.0 mm)77       Figure 4-5 Standard and fast sintering protocols following the manufacturer’s recommendations for sintering IPS e.max ZirCAD LT. The standard program is 9hr in total, while the fast program is 3 hr 30 min in total.  78  The sintering temperatures and rates for standard conventional sintering (SS) are set according to the manufacturer's instructions of IPS e.max ZirCAD material as follows: Drying will be for 2 hours in open, cold furnace at room temperature. In the preheating stage, temperature was raised from 20C to reach 900C at the rate of 600C per hour and held there for 30 minutes. Then temperature was raised again from 900C to reach 1450C at the rate of 200C per hour to reach 1450C. Then the holding (Dwell) time at 1450C was for 120 minutes (2 hours). Then the cooling off was from 1450C to 900 at the rate of 600C per hour and then from 900C to 300C at the rate of 500C per hour. Therefore, the total time required per cycle was equal to 9 hours (Figure 4-5). The sintering temperatures and rates for fast conventional sintering (FS) are set according to the manufacturer’s instructions for IPS e.max ZirCAD material as follows: Drying will be for 2 hours in open, cold furnace at room temperature. In the preheating stage, temperature was raised from 20C to reach 1520C at the rate of 1500C per hour and held there for 30 minutes (Dwell time). Then the cooling off was from 1520C to 300 at the rate of 800C per hour.  Therefore, the total time required per cycle is equal to 210 minutes (~ 3.5 hours) (Figure 4-5).  Sintered crowns were identified according to their codes in the honeycomb sintering carrier and were seated on the respective master titanium abutments occlusally. Standardized criteria were followed to check the internal interferences while seating each crown on the corresponding abutment. The margins of each crown were initially evaluated with a dental explorer (EXD 11/12; Hu-Friedy) and 2.5X magnification loupe (Oroscoptic) and then assessed by using Fit Checker (GC) and a light microscope. All crowns fit freely, without interference. No adjustments were made to the crown intaglio surfaces. 79  4.1.5 Measurement of the Marginal Discrepancy Zirconia crowns were seated on the corresponding master abutments under a standardized load of 500g without cementation. The die was held in a standardized position on a rotating measuring chuck using an alignment clamp to allow reproducibility of the rotational portions for the measurement points. The marginal gaps were assessed according to Holmes et al.’s [66] definition of vertical marginal gap, using a Leica microsystems microscope (ON, Canada) coupled with a digital camera (Leica DMC6200, ON, Canada) at 40X magnification (Figure 4-6).  80   Figure 4-6 An image illustrating the rotating measuring chuck using an alignment clamp and 500g load.  81  Vertical marginal gaps were determined using 8 predetermined measuring points in each abutment (mid-buccal, mid-lingual, mid-mesial, mid-distal) and four line angles (Mesiobuccal (MB), Mesiolingual (ML), Distobuccal (DB), Distolingual (DL)) (Figure 4-7).   Figure 4-7 Measurement locations.   The photographs were taken, and the images were processed with image analysis software (Image J software 1.32; U.S. National Institutes of Health). All measurements were made perpendicular to the crown along the margins (Figure 4-8). 82   Figure 4-8 Buccal marginal gap image taken by the digital microscope and measured using imageJ software.  4.1.6 Statistical Analysis Sample size calculation was based on a power analysis on 5 samples per group and adjusting the sample size to achieve 80% power and 5% significance. Descriptive statistics of medians and means of the vertical marginal gaps for each combination of finish line, crown thickness and sintering were analyzed and computed. R (R Core Team, 2012) was used to perform the linear mixed effect model following two cases: Case I investigated the effect of interaction 83  between finish line width, crown thickness and sintering on the vertical marginal gaps. Case II investigated the interaction between finish line width, crown thickness, sintering and surfaces on vertical marginal gaps. In both cases, Crown# was defined as each sample of fitted zirconia crown on the titanium abutment in each group and was considered the random effect, while the other variables in each case were considering fixed effects. Likelihood ratio test was used to test the significance of interactions in each case and the appropriate model was selected to obtain the estimated means of vertical marginal gaps. When interactions were found significant, multiple comparison (contrast) tests were performed. Diagnostic QQ plots were used to check the homoscedasticity and normality of the data. In addition to likelihood ratio test, ANOVA type III test was produced to report F statistics of the interaction and its corresponding p-value for each case. 4.2 Results Case I: Interaction Between Crown Thickness, Finish Line Width and Sintering Protocol on Vertical Marginal Gaps The median values of the vertical marginal gaps for each combination of finish line, crown thickness and sintering with the entire distribution of observation per group are represented in Figure 4-9. G8 (0.5 mm finish line, 1.5 mm thickness, FS) yielded the largest vertical marginal gaps (median: ~47 m; range: 12-85 m) compared to the other combinations, whereas both G3 (1.0 mm finish line, 0.8 mm thickness, SS) and G4 (1.0 mm finish line, 1.5 mm thickness, SS) demonstrated the smallest vertical marginal gaps (median: ~14 m;  ranges:  4-30 m and 3-40 m, respectively).   84   Figure 4-9 Boxplots of vertical marginal gap values from the different Crown thickness × Finishline × Sintering combinations.  The mean values of vertical marginal gaps for each combination and the crossing lines in the graph indicate the presence of interaction between crown thickness, finish line and sintering represented in Figure 4-10. Standard errors represented by the dotted lines are relatively small. G8 combination (0.5 mm finish line, 1.5 mm thickness, FS) yielded the largest vertical marginal gap mean: 47.9 (1.66) m, compared to the other combinations, whereas both G3 (1.0 mm finish line, 0.8 mm thickness, SS) and G4 (1.0 mm finish line, 1.5 mm thickness, SS) demonstrated the µm 85  smallest vertical marginal gap means: 14.43 (1.66) m and 14.65 (1.66) m, respectively. G7 combination (0.5 mm finish line, 0.8 mm thickness, FS) as a smaller mean 16.66 m compared to G8 (0.5 mm finish line, 1.5 mm thickness, FS) 47.9 (1.66) and G1 (0.5 mm finish line, 0.8 mm thickness, SS) 29.59 (1.66) m.   Figure 4-10 Interaction plot for effect of Length × Finishline × Sintering on Marginal gap. Points on the plot represent mean values of the Marginal gap for each combination of Length × Finishline × Sintering. Dotted lines represent standard errors of the respective mean estimates.  µm 86  Two linear mixed effect models were fitted to test the significance of this interaction by specifying the Crown# as a random effect. Likelihood ratio test for Models 1 and 2 demonstrated that the interaction of finish line × crown thickness × sintering was significant (p <0.001) and Model 2 showed lower Akaike information criterion (AIC=7702) compared to Model 1 AIC (7731) (Table 4-2).   Table 4-2 Likelihood ratio values from testing the effect of the Finish line × Crown thickness × Sintering Model DF AIC BIC logLik Chisq Chi Df Pr(>Chisq) 1* 2** 12 14 7731 7702 7790 7771 -3854 -3837  32.95  2  0.00 *Model 1 (Reduced model) Marginal gap ~ Crown thickness + Finishline + Sintering + Crown thickness × Finishline + Crown thickness × Sintering + Finishline × Sintering + Random Effect (Crown#) **Model 2 (Full model) Marginal gap ~ Crown thickness + Finishline + Sintering + Crown thickness × Finishline + Crown thickness × Sintering + Finishline × Sintering + Finishline × Crown thickness × Sintering + Random Effect (Crown#)   Therefore, Model 2, with finish line × crown thickness × sintering interaction, was used to estimate the mean vertical marginal gaps and its 95%CI for each combination in the different interactions (Table 4-3, Figure 4-11).     87  Table 4-3 Vertical marginal gaps mean estimates for different combinations of CrownThickness (CT) × Finishline depending on the sintering process Group CT Finishline Sintering lsmean SE df lower.CL upper.CL G1 Thin 0.5 SS 29.59 1.656 108 26.30 32.87 G2 Thick 0.5 SS 40.98 1.656 108 37.69 44.26 G3 Thin 1.0 SS 14.43 1.656 108 11.15 17.71 G4 Thick 1.0 SS 14.65 1.656 108 11.37 17.94 G5 Thin 1.2 SS 27.97 1.656 108 24.69 31.25 G6 Thick 1.2 SS 27.11 1.656 108 23.83 30.40 G7 Thin 0.5 FS 16.66 1.656 108 13.38 19.94 G8 Thick 0.5 FS 47.95 1.656 108 44.67 51.23 G9 Thin 1.0 FS 18.25 1.656 108 14.97 21.53 G10 Thick 1.0 FS 18.62 1.656 108 15.34 21.90 G11 Thin 1.2 FS 32.74 1.656 108 29.46 36.02 G12 Thick 1.2 FS 25.51 1.656 108 22.22 28.79 SS: standard sintering; FS: fast sintering  G8 (0.5 mm finish line, 1.5 mm thickness, FS) exhibited the largest estimated mean marginal gaps (47.95 m, 95%CI: 44.57, 51.23), whereas G3 (1.0 mm finish line, 0.8 mm thickness, SS) had the smallest marginal gaps (14.43 m, 95%CI: 11.15, 17.71). The mean marginal gap values of the thick and thin crown thicknesses with the same sintering (FS) and finish 88  line (1.0 chamfer) (i.e. G9 and G10) were not significantly different (18.25 m, 95%CI: 14.97,21.53) and (18.62 m, 95%CI: 15.34,21.90), respectively. Similarly, the estimated mean marginal gaps values for the thick and thin crowns with the same sintering (SS) and finish line (1.0 mm chamfer) (i.e., G3 and G4) seem to be slightly lower but not significantly different than their counterparts that underwent FS, respectively.   Figure 4-11 Estimated mean vertical marginal gap values from Case I, Model 2 for each combination of CrownThickness × Finishline × Sintering to reflect Table 4-3. µm 89   F value for the interaction was found to be 18.96, P<0.001 after checking ANOVA III test. We looked into the ANOVA tables and found that the p values from the F statistics from ANOVA III are not different from the P values obtained from the Chisq statistics in likelihood ratio tests (Table 4-4).  Table 4-4 ANOVA table for Model 2    The multiple comparisons between all the different combinations of crown thickness and finish lines for each sintering protocol are shown in Figure 4-11. In FS groups and within the same crown thickness, all the combinations showed significant interactions except between 0.5 mm and 1 mm finish lines. In contrast, in SS groups and within the same crown thickness, all the combinations showed significant interaction, except between 0.5 mm and 1.2 mm finish lines. The effects of sintering (FS vs. SS) were observed only for 0.5 mm finish line within the same crown thickness groups (p<0.001). For instance, the largest significant difference of estimated marginal 90  gap (31.29 m) was observed between G4 (1.0 mm finish line, 1.5 mm thickness, SS) and G8 (0.5 mm finish line, 1.5 mm thickness, FS) (33.30 m p<0.001) and between G7 (0.5 mm finish line, 0.8 mm thickness, FS) and G8 (0.5 mm finish line, 1.5 mm thickness, FS) (31.29 m p<0.001). The smallest estimated difference (6.973 m) was between G8 (0.5 mm finish line, 1.5 mm thickness, FS) and G2 (0.5 mm finish line, 1.5 mm thickness, SS) (p<0.001). Significant effect was found between similar crown thickness and different sintering protocols except between (G4, G10), (G6, G12), (G3, G9) and (G1, G5) after adjustment for multiple comparisons using the false discovery rate (FDR) method with each level of crown thickness.   Table 4-5 Multiple comparisons between all the different combinations of finish line and sintering for each crown thickness (CT), adjusted by false discovery rate (FDR) method for multiple comparisons within each level of crown thickness. contrast CT estimate SE df t.ratio p.value 0.5,FS - 1,FS Thick 29.33 2.34 108 12.52 0.000 0.5,FS - 1.2,FS Thick 22.44 2.34 108 9.58 0.000 0.5,FS - 0.5,SS Thick 6.97 2.34 108 2.98 0.005 0.5,FS - 1,SS Thick 33.29 2.34 108 14.22 0.000 0.5,FS - 1.2,SS Thick  20.84 2.34 108 8.90 0.000 1,FS - 1.2,FS Thick -6.89 2.34 108 -2.94 0.005 1,FS - 0.5,SS Thick -22.36 2.34 108 -9.54 0.000 1,FS - 1,SS Thick 3.97 2.34 108 1.69 0.100 91  contrast CT estimate SE df t.ratio p.value 1,FS - 1.2,SS Thick -8.49 2.34 108 -3.63 0.001 1.2,FS - 0.5,SS Thick -15.47 2.34 108 -6.61 0.000 1.2,FS - 1,SS Thick 10.85 2.34 108 -4.63 0.000 1.2,FS - 1.2,SS Thick -1.61 2.34 108 -0.69 0.494 0.5,SS - 1,SS Thick 26.32 2.34 108 11.24 0.000 0.5,SS - 1.2,SS Thick 13.86 2.34 108 5.92 0.000 1,SS - 1.2,SS Thick -12.46 2.34 108 -5.32 0.000 0.5,FS - 1,FS Thin -1.59 2.34 108 -0.69 0.499 0.5,FS - 1.2,FS Thin -16.08 2.34 108 11.24 0.000 0.5,FS - 0.5,SS Thin -12.93 2.34 108 5.92 0.000 0.5,FS - 1,SS Thin 2.23 2.34 108 -5.32 0.397 0.5,FS - 1.2,SS Thin -11.31 2.34 108 -4.83 0.000 1,FS - 1.2,FS Thin -14.49 2.34 108 -6.19 0.000 1,FS - 0.5,SS Thin -11.34 2.34 108 -4.84 0.000 1,FS - 1,SS Thin 3.82 2.34 108 1.63 0.145 1,FS - 1.2,SS Thin -9.72 2.34 108 -4.15 0.000 1.2,FS - 0.5,SS Thin 3.16 2.34 108 1.35 0.226 1.2,FS - 1,SS Thin 18.31 2.34 108 7.81 0.000 1.2,FS - 1.2,SS Thin 4.77 2.34 108 2.04 0.066 92  contrast CT estimate SE df t.ratio p.value 0.5,SS - 1,SS Thin 15.15 2.34 108 6.47 0.000 0.5,SS - 1.2,SS Thin 1.62 2.34 108 0.69 0.499 1,SS - 1.2,SS Thin -13.54 2.34 108 -5.78 0.000 SS: standard sintering; FS: fast sintering  Case II: The Relationship Between the Finish Line Widths, Crown Thicknesses, Sintering and Surface on Vertical Marginal Gaps Median values of marginal gaps from the different combinations of finish line, crown thickness, sintering, and surfaces are shown in Figure 4-12. The comparison between the 8 different measurement surfaces showed that the mesial (M) and mesiobuccal (MB) surfaces of similar combinations (1.0 mm finish line, 0.8 mm, SS) exhibited the lowest vertical marginal gaps values (median: ~5 m; range: 1-11 m). The lingual surface of the 0.5 mm finish line, 1.5 mm thickness, FS combination had the largest vertical marginal gaps (median: ~65 m; range: 60-70 m).  93   Figure 4-12 Boxplots of vertical marginal gap values from the different crown thickness × finish line × sintering × surface interactions.  µm 94  The two linear mixed effect models (Model 1` and Model 2`) that were used to fit this interaction showed a significant four-way interaction (p=0.023) (Table 4-6).  Table 4-6 Likelihood ratio values from testing the effect of the Finish line × Crown thickness × Sintering × Surface interactions (Case 2) on the vertical marginal gap following Model 1` and Model 2`. Model Df AIC BIC logLik Chisq Chi Df Pr(>Chisq) 1* 84 7264 7673 -3548    2** 98 7266 7743 -3535 26.39 14 0.0231 *Model 1` (Reduced model) Marginal gap ~ Crown- Thickness + Finish line + Sintering + Surface + Crown Thickness × Finish line + Crown Thickness × Sintering + Crown Thickness × Surface + Crown Thickness × Finish line + Finish line × Sintering + Finish line × Surface + Sintering × Surface + Crown Thickness × Finish line × Sintering + Crown Thickness × Finish line × Surface + Finish line × Sintering × Surface + Crown Thickness × Sintering × Surface + Random Effect (Crown#)  **Model 2` (Full model) Marginal gap ~ Crown Thickness + Finish line + Sintering + Surface + Crown Thickness × Finish line + Crown Thickness × Sintering + Crown Thickness × Surface + Crown Thickness × Finish line + Finish line × Sintering+ Finish line × Surface + Sintering × Surface + Crown Thickness × Finish line × Sintering + Crown Thickness × Finish line × Surface + Finish line × Sintering × Surface + Crown Thickness × Sintering × Surface + Crown Thickness × Finish line × Sintering × Surface + Random Effect (Crown#)       95  F value for the interaction was reported to be 1.91, P<0.022 after checking ANOVA test. We looked into the ANOVA tables and we found that the p values from the F statistics from ANOVA III are not different from the P values obtained from the Chisq statistics in likelihood ratio tests (Table 4-7).  Table 4-7 ANOVA test for Model 2`.  However, Model 2` was selected, and the interaction was interpreted as a conditional effect (i.e., the estimated mean vertical marginal gaps difference between the crown thickness × finish line × sintering depends on the surface). Therefore, this means that the estimated vertical marginal gap means the difference between the crown thickness × finish line × sintering is not the same for 96  all eight different surfaces. The combination of 1.0 mm finish line, 1.5 mm crown thickness, FS and L surface is significant (31.58 m with 95%CI: 25.13-38.04), while the combination of 1.2 mm finish line, 0.8 mm crown thickness, SS and M surface is insignificant (6.10 m with 95%CI: -0.35,12.56).   Table 4-8 Vertical marginal gap mean estimates for different combinations of CrownThickness × Finishline × Sintering × Surface (case 2). CrownThickness Finishline Sintering Surface Mean lower.CL upper.CL Thick 0.5 Fast B 41.87 35.42 48.33 Thin 0.5 Fast B 25.20 18.75 31.65 Thick 1 Fast B 14.79 8.33 21.24 Thin 1 Fast B 17.50 11.05 23.96 Thick 1.2 Fast B 24.12 17.67 30.58 Thin 1.2 Fast B 35.58 29.13 42.04 Thick 0.5 Standard B 44.72 38.27 51.18 Thin 0.5 Standard B 31.10 24.65 37.55 Thick 1 Standard B 15.08 8.62 21.53 Thin 1 Standard B 21.19 14.73 27.64 Thick 1.2 Standard B 30.04 23.59 36.49 Thin 1.2 Standard B 30.62 24.17 37.08 Thick 0.5 Fast D 61.07 54.61 67.52 97  CrownThickness Finishline Sintering Surface Mean lower.CL upper.CL Thin 0.5 Fast D 18.45 11.99 24.90 Thick 1 Fast D 16.48 10.03 22.93 Thin 1 Fast D 22.53 16.07 28.98 Thick 1.2 Fast D 27.20 20.75 33.65 Thin 1.2 Fast D 39.51 33.05 45.96 Thick 0.5 Standard D 46.28 39.82 52.73 Thin 0.5 Standard D 36.06 29.60 42.51 Thick 1 Standard D 12.17 5.71 18.62 Thin 1 Standard D 16.12 9.67 22.58 Thick 1.2 Standard D 30.07 23.61 36.52 Thin 1.2 Standard D 38.28 31.83 44.73 Thick 0.5 Fast DB 57.24 50.78 63.69 Thin 0.5 Fast DB 21.88 15.43 28.34 Thick 1 Fast DB 19.56 13.10 26.01 Thin 1 Fast DB 20.39 13.94 26.85 Thick 1.2 Fast DB 30.95 24.49 37.40 Thin 1.2 Fast DB 41.74 35.29 48.20 Thick 0.5 Standard DB 57.02 50.56 63.47 Thin 0.5 Standard DB 40.72 34.27 47.17 98  CrownThickness Finishline Sintering Surface Mean lower.CL upper.CL Thick 1 Standard DB 13.84 7.39 20.30 Thin 1 Standard DB 15.80 9.35 22.26 Thick 1.2 Standard DB 31.88 25.42 38.33 Thin 1.2 Standard DB 41.48 35.02 47.93 Thick 0.5 Fast DL 57.71 51.26 64.16 Thin 0.5 Fast DL 16.21 9.75 22.66 Thick 1 Fast DL 19.61 13.16 26.07 Thin 1 Fast DL 16.54 10.09 23.00 Thick 1.2 Fast DL 31.60 25.15 38.06 Thin 1.2 Fast DL 41.20 34.74 47.65 Thick 0.5 Standard DL 43.79 37.34 50.24 Thin 0.5 Standard DL 31.40 24.95 37.85 Thick 1 Standard DL 13.08 6.63 19.53 Thin 1 Standard DL 15.61 9.16 22.06 Thick 1.2 Standard DL 31.89 25.43 38.34 Thin 1.2 Standard DL 33.85 27.40 40.31 Thick 0.5 Fast L 64.54 58.09 70.99 Thin 0.5 Fast L 14.67 8.22 21.13 Thick 1 Fast L 31.58 25.13 38.04 99  CrownThickness Finishline Sintering Surface Mean lower.CL upper.CL Thin 1 Fast L 22.81 16.35 29.26 Thick 1.2 Fast L 29.80 23.34 36.25 Thin 1.2 Fast L 40.38 33.93 46.84 Thick 0.5 Standard L 49.51 43.06 55.97 Thin 0.5 Standard L 39.01 32.55 45.46 Thick 1 Standard L 30.28 23.83 36.73 Thin 1 Standard L 22.87 16.41 29.32 Thick 1.2 Standard L 33.19 26.74 39.64 Thin 1.2 Standard L 34.80 28.35 41.25 Thick 0.5 Fast M 28.84 22.39 35.30 Thin 0.5 Fast M 7.47 1.01 13.92 Thick 1 Fast M 12.41 5.96 18.87 Thin 1 Fast M 12.07 5.62 18.52 Thick 1.2 Fast M 15.86 9.40 22.31 Thin 1.2 Fast M 16.89 10.44 23.34 Thick 0.5 Standard M 23.36 16.91 29.82 Thin 0.5 Standard M 11.88 5.43 18.34 Thick 1 Standard M 6.95 0.49 13.40 Thin 1 Standard M 4.61 -1.84 11.07 100  CrownThickness Finishline Sintering Surface Mean lower.CL upper.CL Thick 1.2 Standard M 15.04 8.58 21.49 Thin 1.2 Standard M 6.10 -0.35 12.56 Thick 0.5 Fast MB 24.35 17.90 30.80 Thin 0.5 Fast MB 10.68 4.23 17.14 Thick 1 Fast MB 10.33 3.88 16.79 Thin 1 Fast MB 13.72 7.26 20.17 Thick 1.2 Fast MB 16.69 10.23 23.14 Thin 1.2 Fast MB 22.27 15.82 28.72 Thick 0.5 Standard MB 21.52 15.07 27.98 Thin 0.5 Standard MB 11.00 4.55 17.45 Thick 1 Standard MB 7.02 0.57 13.47 Thin 1 Standard MB 5.21 -1.24 11.67 Thick 1.2 Standard MB 15.62 9.16 22.07 Thin 1.2 Standard MB 16.26 9.81 22.71 Thick 0.5 Fast ML 47.98 41.52 54.43 Thin 0.5 Fast ML 18.72 12.26 25.17 Thick 1 Fast ML 24.20 17.74 30.65 Thin 1 Fast ML 20.43 13.98 26.89 Thick 1.2 Fast ML 27.84 21.39 34.30 101  CrownThickness Finishline Sintering Surface Mean lower.CL upper.CL Thin 1.2 Fast ML 24.36 17.91 30.81 Thick 0.5 Standard ML 41.61 35.16 48.06 Thin 0.5 Standard ML 35.51 29.06 41.96 Thick 1 Standard ML 18.82 12.37 25.27 Thin 1 Standard ML 14.04 7.58 20.49 Thick 1.2 Standard ML 29.20 22.74 35.65 Thin 1.2 Standard ML 22.37 15.91 28.82   102   Figure 4-13 Estimated mean vertical marginal gap values from Case II, Model 2` by the different Crown Thickness × Finish line × Sintering × Surface combinations. µm 103  4.3 Discussion To the authors’ best knowledge, this is the first study to investigate the effects of SS and FS protocols on the marginal fit of monolithic FCZ crowns. The results of this study revealed a significant interaction between different finish line widths, crown thicknesses, and sintering on vertical marginal gaps. Therefore, the null hypothesis was rejected. Precision of fit, marginally and internally, is a fundamental element for the long-term clinical success of dental restorations [66]. There are several approaches to assess the fit of prostheses including direct view technique using external microscope [28, 142], cross-sectioning [62], replica technique [143], profile projector [144], and microtomography [111, 142, 145-147]. However, most of the studies have assessed the marginal fit of zirconia prosthesis with external microscopes [57, 113, 117, 125] and the internal fit with either internal microscopes [114, 119, 124, 148, 149] or replica technique [113, 115, 129, 143, 150, 151]. In this study, we measured the marginal gaps by optical microscope due to its non-destructive nature, feasibility and practicality. Some studies confirmed the similarity between direct external and internal viewing techniques in measuring marginal fit of zirconia crowns and indicated that using the external viewing is adequate and accurate for measuring the marginal fit without the need of destroying the specimens [102]. It should be noted that comparing the marginal gap results from different studies is difficult because of the high variability in the methodologies that included using different fabrication systems, types of cements and method for assessing the fit [28]. The use of customized implant abutment with curved margins in this study may have facilitated attaining a more clinically relevant conclusion. However, it has been reported that a variation of the alignment between the plane of the marginal preparation and the focal plane of the microscope could cause projection error [138], especially with a more clinically-relevant curved 104  margin compared to a sharp-defined margin. This could explain better results obtained from the experimental crowns, where it is easier to align the focal plane of the microscope. This study analyzed the marginal gap measurements using linear mixed effects model to investigate the interaction between more than two factors in order to consider the high variability within each crown (cluster effect). To the authors’ best knowledge, this is the first study utilizing this model to test the combined effect of three or four factors on marginal gaps. Because the data is balanced between the groups, and we only have one random effect, a repeated measures ANOVA could be an alternative statistical analysis. However, compared to repeated measures ANOVA, linear mixed effects model is a more flexible and powerful approach to dealing with repeated measures because it avoids oversimplifying restrictions on the correlation structures [13, 152].  Using the linear mixed effects model ensures that the complexity of the data structure is handled appropriately, thus producing reliable estimates for the mean marginal gaps for different combinations of the tested factors. Our findings indicated that the G8 (FS, 0.5 mm chamfer, 1.5 mm thickness) had the largest vertical marginal gap values, which is therefore larger than the corresponding SS group (G2). In general, FS showed larger gap values compared to the corresponding combinations of SS except at 0.5 mm finish line, thin crowns. This could be due to the increase of the sintering temperature from 1450C to 1520C, since the creep of zirconia depends on both temperature and stress [153]. Due to the fact that zirconia creep rate increases exponentially with increased temperature, it was believed that this combination was more sensitive to creep and distortion during sintering compared to thinner crowns on a narrower surface area. This is consequently expressed as a larger marginal gap. The complex three-dimensional shape of the crowns did not allow any further quantitative analysis of the combined effects of gravitational stress and temperature of the creep 105  rate at different locations on the crown in this work. However, complex analysis of this phenomenon by Finite Elements Method could lead to more precise correlations between crown distortion in different locations, method of the crown placement in the furnace, and the sintering parameters, in particular the rate of temperature increase, and the maximum sintering temperatures/times; this is suggested for future work. On the other hand, the G3 (SS, 1.0 mm chamfer, 0.8 thickness) exhibited the smallest estimated marginal gaps, which was almost similar to the combination of G4. The 1.0 mm finish line had lower marginal gaps and more consistent results in both sintering groups compared to 0.5 mm finish line, which showed more sensitive tendency to sintering protocol. This is probably due to the reduced stresses by having bulkier zirconia at 1.0 mm finish line compared to 0.5 mm, since thicker finish line width leads to decreased internal stresses [153]. Indeed, our results showed a significant decrease in vertical marginal gaps as the finish line widths increased from 0.5 mm to 1.2 mm. In the mixed effect model that included the surface interactions, the mesial and mesiobuccal surfaces exhibited the lowest marginal gaps while the lingual surface presented the highest marginal gaps. This could be attributed to the direction of placement of the crowns inside the sintering oven toward the occlusal side and under the gravitation effect, leading to a greater marginal discrepancy than is found on those sites. In contrary, a previous study using Lava chair-side oral scanner to measure the vertical marginal gaps demonstrated that the mesial surfaces of zirconia crowns with chamfer preparation had the biggest mean vertical marginal gaps, 23.88 ±19.16 µm, and the lingual surface showed the lowest mean vertical marginal gaps, 16.37 ±6.06 µm [57]. This could be explained by the different methodology between the studies. In the previous study,[57] the crown thickness was 2.0 mm and the authors did not mention the position of the 106  crown inside the oven. Even though the acceptable marginal gap has been debated in the literature, the results of this study (14.43 to 47.95 m 95%CI: 11.15, 51.23) fall within the clinically acceptable marginal gap.[63-65]. Khaledi et al. [154] evaluated the effect of three different sintering times using a single 1530C sintering temperature and found no significant influence of sintering times on marginal fit on the marginal fit of zirconia 3-YTZP copings. The results of this study, however, showed that FS resulted in greater marginal gaps than standard sintering protocol. The contrasting results may be attributed to the different sintering protocols used and other methodological differences between the studies. It has been shown that increasing the sintering temperature and decreasing the time yields a better translucency of the sintered dental zirconia ceramics [80-82, 84, 85, 155]. However, the reported results are inconclusive regarding the relationship between the increased sintering temperature and flexural strength [156]. In addition, it seems that accelerated sintering may result in poor wear behavior compared to the “long-term” sintering [81]. It is clear, however, that for improved productivity, fast sintering would be beneficial, as it decreases the time of manufacturing process for zirconia prostheses. Further studies are required to assess the effects of sintering times and temperature on the mechanical, microsctructure and optical properties of zirconia prosthesis. One of the limitations of this study is that all crowns were fabricated under close to “ideal” conditions to decrease the number of possible confounding factors; however, this might not reflect the daily clinical practice. Another limitation is that the method used to measure the marginal gap does not allow the measurement of absolute marginal gap, which according to Holmes et al. [66] is considered the best alternative estimation of the marginal gap, since it reflects the total crown misfit (vertically and horizontally). Such an approach was not used in this study because it would 107  require the sectioning and destruction of the crown, hence not allowing use of the same crown for the other experiments. Another limitation is that the results cannot be generalized to all zirconia brands as only one type of zirconia was tested in this study (e.g., the creep deformation rates of other zirconia, with different content of minor impurities such as silica at grain boundaries, might be different). Finally, the crowns tested in this study were not cemented during the measurements of the marginal fit, whereas the cementation is known to increase the marginal gap. These limitations make generalization of the results to clinical applications somewhat difficult. Future more comprehensive studies are needed to overcome these limitations and to investigate the effects of the position of different types of zirconia prostheses inside the sintering oven, and on the sintering shrinkage protocols and marginal adaptation.  4.4 Conclusions There was a significant interaction between the finish line widths, the crown thickness, and the sintering protocol on the vertical marginal gap. All vertical marginal gap measurements were, however, within the clinically acceptable range. The combination of 1.0 mm finish line preparations with either 0.8 mm or 1.5 mm crown thickness had better marginal fit in both sintering protocols (standard or fast) compared to crowns with 0.5 or 1.2 mm finish lines. Standard sintering showed smaller vertical marginal gaps values compared to the corresponding combinations of FS except at 0.5 mm finish line. Smaller marginal discrepancies were observed for standard sintering for zirconia crown preparations with a 0.5mm finish line and 1.5mm occlusal reduction. Conservative occlusal reduction should be accompanied with a 1.2mm finish line to obtain better marginal fit for when using IPS e.max ZirCAD LT blanks for zirconia crowns.  108  Chapter 5: Dimensional Changes of Yttria-stabilized Zirconia under Different Preparation Designs and Sintering Protocols  5.1 Purpose Zirconia gained a significant clinical acceptance for use in indirect dental prostheses because of the simplicity of its fabrication, white color and superior mechanical properties [157]. It has been recognized that processing of zirconia results in distortions of the structure due to high temperature sintering [3]. Alteration of sintering parameters has been found to alter the microstructural [40, 42-44], mechanical [40, 42, 43, 53, 76, 80, 81] and optical [42, 80-85] properties of zirconia. Increasing sintering temperature to 1550ºC (from the typical dwell sintering temperature of 1450ºC) and decreasing sintering time to 30 min (from the typical sintering time of 120 min) improves light transmission and decreases the contrast ratio, and therefore enhances the optical properties of 3 mol% yttria-stabilized zirconia [157], but also has negative effects on its mechanical properties [40]. Moreover, reduced-time sintering protocol, i.e., heat-up rate of 1500ºC/hr (vs. the standard slow sintering heat up of 600ºC/hr followed with 200ºC/hr) generally resulted in larger marginal gaps compared to standard sintering protocol except at the thin marginal finish-line and occlusal reductions of 0.8 mm [94]. A recently published article has indirectly investigated the distortion of zirconia crowns during processing by determining the marginal fit of zirconia crowns prepared under the influence of different preparation designs and different sintering protocols [94]. In this study, we directly investigated the linear and volumetric dimensional changes of zirconia copings under the same influencing factors.  109  There is currently a lack of studies that evaluate the alteration of dimensions of zirconia during the three processing stages (design, milling and sintering). Furthermore, it is not known if the pre-established degree of enlargement at the milling stage is equivalent to the degree of shrinking after sintering when using different sintering protocols. The aim of this study was to evaluate the linear and volumetric dimensional changes that occur through the process of fabricating monolithic zirconia copings using CAD/CAM and to compare the effects of standard and fast sintering protocols. The null hypothesis was that there were no significant differences in the volumetric and linear dimensional changes of zirconia copings, regardless of the combination of coping thickness, finish line offset and sintering protocols.  5.2 Material and Methods  5.2.1 Fabrication of the Master Dies  One digitally customized, machined-milled titanium core file Atlantis implant-abutment from Dentsply Sirona mimicking mandibular molar crown preparation was used to fabricate one master abutment. The Atlantis abutment core file from Dentsply Sirona Implants was chosen because it eliminated the need to scan the titanium abutment after the milling process. A scan body (FLO, Atlantis, Waltham) was placed on a mandibular working model with an Astra implant on the location of #46. A dental laboratory scanner (3 Series scanner, Dental Wings, Canada) was used to scan the mandibular model and the scan body once and then use the “order later feature” from Atlantis to order the abutment (Figure 5-1).   110   Figure 5-1. Illustrations showing the digital fabrication process of the core file abutment. A dental laboratory scanner was used to scan the model and Atlantis FLO was used to order the abutments (Left). Dental Wing software was used to import the core files and design the master abutment.  The occlusal angle of convergence was 12 and the height was 5 mm. Emergence shape and width were set as a default. The margin was 1.0 mm chamfer finish line. The die was constructed with a semi-anatomical occlusal surface. The master abutment was transferred to a manufacture milling unit (CAM) (Atlantis Milling Center, Waltham, Massachusetts, USA) that accepts open-format Stereolithography (.stl) to be milled and reproduced in titanium master abutments (Figure 5-2).   111   Figure 5-2 Photograph showing the Atlantis titanium abutment.  5.2.2 Coping Fabrication  A simulated cement spacer was set at 0 m at the margin and at 30 m at 1 mm above the margin and elsewhere (Figure 5-3).    Figure 5-3 Schematic example showing the different parameters used to set the cement thickness marginally and internally in the digitally designed monolithic zirconia coping (all dimensions in mm).  112  Six copings were designed virtually with three different thicknesses (0.5, 1.0, 1.5 mm) and two finish line offsets (0.5 and 1.2 mm) (Figure 5-4). The copings were designed with uniform thicknesses, without occlusal anatomy.    Figure 5-4 Schematic example showing the software interface for designing the different coping dimensions.  Four reference posts were designed in the virtual design of core files. The four cone-shaped posts on the occlusal were positioned at the occlusal/axial intersection edge, equidistant, parallel and labeled as A, B, C, and D; .stl files were created from the six coping designs, to be measured virtually using Meshmixer software. The distances between AB, BC, CD, and DA at the four different posts were taken virtually and the measuring points were determined to be at the centers of the apices by using Meshmixer analysis tool (Figure 5-5).   113   Figure 5-5 Schematic illustrating AB, BC, CD, DA linear measurements in mm.  The digital files were then transferred to a third-party five-axis milling machine (Wield Select, Ivoclar Vivadent, Schaan, Liechtenstein) at the Ivoclar Vivadent dental milling center (NY, USA) for the zirconia blanks to be milled, and the same milling machine was always used. IPS e-max ZirCAD LT zirconia blanks (Ivoclar Vivadent, NY, USA) were used to mill twelve copings per design (n=12) by soft-milling technique. The milling machine software is programmed to account for the shrinkage of the partially sintered zirconia blanks after final sintering. Each blank possesses a specific barcode accounting for the anticipated post-sintering shrinkage that is determined during manufacturing of the blank. Therefore, the milled crown would be larger than the planned design by 20-25% as claimed by the manufacture. After the pre-sintered zirconia copings were milled, the pieces were separated from the blanks using diamond burs and gently ground with fine-grain emery paper. The 72 copings were scanned before sintering using an intra-oral scanner (3Shape Trios, Inc., NY, USA) [158]. Each coping was held by a veneer holding stick 114  from the intaglio surface (Figure 5-6) and all coping surfaces were scanned, including the veneer stick area. All samples were held at the same orientation and the intra-oral scanner tip was moving around the sample at the same path to capture the surfaces. The stick was removed from the intaglio surface and reattached to the distal surface and an over-scan was taken again to the intaglio surface to remove the veneer stick and capture the inner side of the coping. The .stl files were created and then transferred to be measured virtually using Meshmixer software.    Figure 5-6 An image illustrating how the samples were held by the veneer stick during scanning process.  5.2.3 Experimental groups The experimental groups according to the coping designs were the following: G1: 0.5 mm finish line offset, 0.5 mm thickness; G2: 0.5 mm finish line offset, 1.0 mm thickness; G3: 0.5 mm finish line offset, 1.5 mm thickness; G4: 1.2 mm finish line offset, 0.5 mm thickness; G5: 1.2 mm finish line offset, 1.0 mm thickness; G6: 1.2 mm finish line offset, 1.5 mm thickness. From six test groups, 12 samples per design, six samples were randomly selected for standard sintering (SS) and 115  the other six were randomly selected for fast sintering (FS). Each sample had four equal linear measurements n=24 and one volumetric value n=12 per group (Table 5-1, Figure 5-7).  Table 5-1 Experimental groups according to the coping designs Group Finish line offset Coping thickness 1 0.5 mm 0.5 mm 2 0.5 mm 1.0 mm 3 0.5 mm 1.5 mm 4 1.2 mm 0.5 mm 5 1.2 mm 1.0 mm 6 1.2 mm 1.5 mm  116   Figure 5-7 Experimental groups with different coping dimensions and the four posts showing in Meshmixer software.  5.2.4 Sintering Procedure Protocol  The soft-mill copings were sintered according to the manufacturer’s recommended sintering protocols using the same conventional sintering furnace (Programat S1 Furnace, Ivoclar Vivadent, NY, USA). Enlarged copings were positioned on the marginal surface. Six copings from each group were sintered by standard sintering (SS) protocol and the other six copings were sintered following a fast sintering (FS) protocol (Figure 5-8).    117     Figure 5-8 Standard and fast sintering protocols following the manufacturer’s recommendations. The standard program is 9hr in total, while the fast program is 3 hr 30 min in total.  118  Sintered copings were identified according to their codes in the honeycomb sintering carrier. After sintering, the margins and posts of each coping were initially evaluated with a dental explorer (EXD 11/12; Hu-Friedy) and 2.5X magnification loupe (Oroscoptic) to exclude any coping with chipping. No adjustments were made to the crown intaglio surfaces. A Trios 3Shape Scanner was used again to scan the post-sintered 72 copings and create post-sintering .stl files. Meshmixer was used to take the same measurements virtually in each of the three stages, baseline (Stage 0), after milling (Stage 1), and after sintering (Stage 2) stages.  The baseline (Stage 0) is not a result of any experimental factor, but just the dimensions occurring originally by designing the prosthesis. Milling stage (Stage 1) is determined by the factory enlargement factor, so it is expectedly significantly larger than baseline. The final stage (Stage 2) is the actual outcome of the effects of design and sintering experimental variables. Of importance to our study are the average linear differences between baseline and final for each combination of designs and also the volumetric differences between baseline and final. The differences between Stage 1 (after milling) and Stage 2 (the final) served to assess and evaluate the accuracy of the manufacturer’s indication of the enlargement/shrinkage factor. Furthermore, it was less important to compare the milling stage and final stage differences between the six groups. However, it was important to determine the discrepancies between the baseline and final stages. 5.2.5 Measurement of the Dimensional Changes  The primary outcome of the experiments was the linear measurements between the four posts located on the occlusal at the occlusal/axial intersection edge. Linear measurements were taken virtually using the Meshmixer software at three stages (the design stage, after milling without sintering and then after sintering (Figure 5-9). Selecting the “Analysis → Units/dimensions” option in the software menu allowed placing points at the center of the apex by providing a circle around 119  each point. This facilitated determining consistent measurements at the center of the apices for linear measurements (mm). The readings were validated by evaluating known distances using the digital caliper and the tolerance calculated to be +/-20m.     Figure 5-9 Schematic illustrating the methodology of the linear measurements DA a) at the design stage, b) at the milling stage, and c) at the sintering stag of G1 in Meshmixer software.  The secondary outcome of the volumetric measurements was also obtained from scanning the twelve samples in each group using Trios intraoral scanner (3Shape Trios, Inc., NY, USA) [158] at the three stages and then processing them after digital 3D construction using Meshmixer software (Figure 5-10). Selecting the “Analysis→ Stability” option allowed calculation of the volumetric measurements (mm3) for the constructed 3D object.  The readings were validated by evaluating known volumes using image analysis software (Image J software 1.32; U.S. National Institutes of Health) and the tolerance calculated to be +/- 0.004 mm3.  120   Figure 5-10 Schematic illustrating the methodology of the volumetric measurements a) at the design stage, b) at the milling stage, and c) at the sintering stage of G3 in Meshmixer software.   5.2.6 Statistical Analysis  Descriptive statistics of medians and means of the linear and volumetric dimensional changes for each combination of design, sintering and stage were analyzed and computed. The results of the measurements during the three stages, the virtual design, milled coping prior to sintering and the sintered copings, were recorded and analyzed by linear mixed effect model. The four linear measurements per sample were treated as repeated measures. The dimensional changes were compared between the stages and between the sintering methods. Descriptive plots were used to inspect the interaction effect visually before fitting the model. After the model was fitted, plots using estimates from the model were generated to compare the overall mean dimensional changes of standard sintered groups versus fast sintered groups. When interactions were found significant using a linear mixed effect model, multiple comparison tests (Post hoc tests) were performed. Diagnostic QQ plots were used to check the homoscedasticity and normality of the residuals and random effects. Statistical analysis was performed via statistical software R (R Core team, 2018; tidyverse, Hadley Wickham, 2017 [159]; lmerTest Package, Kuznetsova A et al., 2017 [160]; DHARMa, Florian Hartig, 2019 [161]; Emmeans, Russell Lenth, 2019 [162]).  121  5.3 Results  5.3.1 Primary Outcome: Interaction Between Coping Design (Group), Sintering (Sintering) and Processing Stage (Stage) on Linear Measurements (LM) The median values of the LM for each combination of Group, Sintering and Stage with the entire distribution of observation per each combination are presented in Figure 5-11. The combination of G1 (0.5 mm finish line offset, 0.5 mm thickness) with SS and the combination of G6 (1.2 mm finish line offset, 1.5 mm thickness) with SS resulted in the smallest linear differences between Stage 0 and 2. On the other hand, the combination of G4 (1.2 mm finish line offset, 0.5 mm thickness) with FS resulted in the largest linear differences between Stage 0 and 2 with a wide variance.  Figure 5-11. Linear measure (mm) median by Group, Sintering and Stage.  The mean values of LM for each combination and the crossing lines in the graph between both sintering protocols indicate the presence of interaction between group, sintering and stages mm 122  represented in Figure 5-12. G1 (0.5 mm finish line offset, 0.5 mm thickness) yielded the smallest LM mean difference between SS and FS at the three stages. The largest LM mean difference between SS and FS at sintered stage 2 was at G4 (1.2 mm finish line offset, 0.5 mm thickness).     Figure 5-12. Interaction plot of Linear measure (mm) by Group  Sintering  Stage. Points on the plot represent mean values of the LM for each combination of Group  Stage. Vertical dotted lines represent standard errors of the respective mean estimates.       mm 123  Table 5-2. Descriptive table of the average percentage change between each of the stages for each combination of the Group and Sintering. Columns LM_St0,LM_St1,LM_St2 correspond to average LM for each stage, and for each combination of Group and Sintering. Stages Group sin LM_St0 mm LM_St1 mm LM_St2 mm Percentage Change % 0--1 1 FS 3.65 4.50 NA 23.30 0--1 1 SS 3.65 4.48 NA 22.77 0--1 2 FS 3.67 4.48 NA 22.20 0--1 2 SS 3.67 4.53 NA 23.42 0--1 3 FS 3.68 4.50 NA 22.27 0--1 3 SS 3.68 4.48 NA 21.78 0--1 4 FS 3.69 4.48 NA 21.48 0--1 4 SS 3.69 4.47 NA 21.19 0--1 5 FS 3.68 4.47 NA 21.63 0--1 5 SS 3.68 4.52 NA 22.91 0--1 6 FS 3.70 4.52 NA 22.41 0--1 6 SS 3.70 4.48 NA 21.35 1--2 1 FS NA 4.50 3.62 -19.63 1--2 1 SS NA 4.48 3.63 -19.09 1--2 2 FS NA 4.48 3.62 -19.39 1--2 2 SS NA 4.53 3.63 -19.95 1--2 3 FS NA 4.50 3.63 -19.26 124  1--2 3 SS NA 4.48 3.61 -19.41 1--2 4 FS NA 4.48 3.61 -19.53 1--2 4 SS NA 4.47 3.63 -18.76 1--2 5 FS NA 4.47 3.60 -19.42 1--2 5 SS NA 4.52 3.61 -20.20 1--2 6 FS NA 4.52 3.65 -19.24 1--2 6 SS NA 4.48 3.67 -18.11 2--1 1 FS NA 4.50 3.62 24.42 2--1 1 SS NA 4.48 3.63 23.59 2--1 2 FS NA 4.48 3.62 24.05 2--1 2 SS NA 4.53 3.63 24.93 2--1 3 FS NA 4.50 3.63 23.86 2--1 3 SS NA 4.48 3.61 24.09 2--1 4 FS NA 4.48 3.61 24.27 2--1 4 SS NA 4.47 3.63 23.10 2--1 5 FS NA 4.47 3.60 24.10 2--1 5 SS NA 4.52 3.61 25.31 2--1 6 FS NA 4.52 3.65 23.83 2--1 6 SS NA 4.48 3.67 22.12 0--2 1 FS 3.65 NA 3.62 -0.90 0--2 1 SS 3.65 NA 3.63 -0.66 125  0--2 2 FS 3.67 NA 3.62 -1.50 0--2 2 SS 3.67 NA 3.63 -1.20 0--2 3 FS 3.68 NA 3.63 -1.28 0--2 3 SS 3.68 NA 3.61 -1.86 0--2 4 FS 3.69 NA 3.61 -2.25 0--2 4 SS 3.69 NA 3.63 -1.55 0--2 5 FS 3.68 NA 3.60 -1.99 0--2 5 SS 3.68 NA 3.61 -1.91 0--2 6 FS 3.70 NA 3.65 -1.15 0--2 6 SS 3.70 NA 3.67 -0.63 2--0 1 FS 3.65 NA 3.62 0.90 2--0 1 SS 3.65 NA 3.63 0.66 2--0 2 FS 3.67 NA 3.62 1.50 2--0 2 SS 3.67 NA 3.63 1.20 2--0 3 FS 3.68 NA 3.63 1.28 2--0 3 SS 3.68 NA 3.61 1.86 2--0 4 FS 3.69 NA 3.61 2.25 2--0 4 SS 3.69 NA 3.63 1.55 2--0 5 FS 3.68 NA 3.60 1.99 2--0 5 SS 3.68 NA 3.61 1.91 2--0 6 FS 3.70 NA 3.65 1.15 126  2--0 6 SS 3.70 NA 3.67 0.63 LM: Linear measurements, St0: Design Stage, St1: Milling Stage, St2: Sintering Stage  Table 5-3. Descriptive table of the average percentage change between each of the stages for each Sintering method averaged over the 6 Groups. Columns LM_St0,LM_St1,LM_St2 correspond to average LM for each stage, grouped by sintering method while taking average over the 6 groups.  Stages sin LM_St0 mm LM_St1 mm LM_St2 mm Percentage Change % 0--1 FS 3.68 4.49 NA 22.21 0--1 SS 3.68 4.49 NA 22.24 1--2 FS NA 4.49 3.62 -19.41 1--2 SS NA 4.49 3.63 -19.26 2--1 FS NA 4.49 3.62 24.09 2--1 SS NA 4.49 3.63 23.85 0--2 FS 3.68 NA 3.62 -1.51 0--2 SS 3.68 NA 3.63 -1.30 2--0 FS 3.68 NA 3.62 1.54 2--0 SS 3.68 NA 3.63 1.32 LM: Linear measurements, St0: Design Stage, St1: Milling Stage, St2: Sintering Stage  It was clear from Figures 5-11 and 5-12 and Tables 5-2 and 5-3 that the average linear distances between the post apices enlarged significantly from the design to the milled by 22.24 % within SS groups and 22.21 % within FS. The linear distances of the final, sintered specimens were reduced, in average 19.26 % within SS and 19.41 % within FS upon sintering. In another word, 127  the linear percentage changes between stage 2 and 1 were in average 23.85 % within SS and 24.09 % within FS upon sintering. The linear percentage differences between the final, sintered specimens were, in average 1.32 % within SS and 1.54 % within FS, smaller than the original design for all the groups. G1 SS and G6 SS presented the smallest percentage difference at Stage 2 compared to Stage 0 and G4 FS showed the largest percentage difference at Stage 2 compared to Stage 0. The significance of interaction between group, stage and sintering was tested by a linear mixed effect model using ANOVA Type 3 table (Table 5-4, Figure 5-13). The model was specified with linear measurement as a response variable, three-way interaction Stage  Group  Sintering, three two-way interactions Stage  Group, Stage  Sintering and Sintering  Group, main effects for Stage, Group and Sintering and random effects for Sample and Distance to control for the correlation between observations within Sample and Distance. The ANOVA Type 3 table for the three-way interaction from the model demonstrated that the interaction of Group x Sintering × Stage was significant (F value =4.451, p value <0.001). Therefore, the model was used to estimate the mean LM and its 95% confidence interval (CI) for each combination in the tested three-way interaction.       128  Table 5-4 ANOVA type 3 table to test the significance of the three-way interaction from the linear model. Linear measurement ~ Stage+Group+Sintering+Stage  Group+Stage  Sintering+Group  sintering+Stage  Group  Sintering + RE(Sample) + RE(Distance)                  129  Table 5-5 Estimated coefficients for the three-way interaction, three two-way interactions and main effects from the linear model mixed effect model: Linear measurement ~ Stage+Group+Sintering+Stage  Group+Stage  Sintering+Group  sintering+Stage  Group  Sintering + RE(Sample)+ RE(Distance)  130   Figure 5-13. Estimated mean Linear measure (mm) by Group  Sintering  Stage interaction from the model.  Multiple comparisons were run to compare the two Sintering methods within each Group and at each Stage (Figures 5-14, 5-15, and 5-16). No multiple testing adjustment was done here because there is only one comparison of FS versus SS for each Group at each Stage. Within stage 2, FS is significantly different than SS at G4 (1.2 mm finish line offset, 0.5 mm thickness) mm 131  (p_value = 0.025). In addition, the 95% confidence intervals of the above differences did not contain 0. Pairwise Stage differences were performed for each combination of Group and Sintering. Multiple testing adjustment of the p-values was performed for three tests using False Discovery Rate (FDR), since there are three pairwise Stage comparisons within each combination of Group and Sintering. The pairwise comparisons between processing stages (Stage) showed significant differences in all combinations of Group and Sintering. However, the largest p-values of 0.04 and 0.03 of linear changes between stage 0 and 2 were observed for G6 (1.2 mm finish line offset, 1.5 mm thickness) with SS and G1 (0.5 mm finish line offset, 0.5 mm thickness) with SS, respectively. The rest of the p-values were <0.001. In addition, 95% confidence intervals of all the estimated differences did not contain 0. This means that significant linear discrepancies between the design and the milled, fully sintered prosthesis were observed when the design was G4 (1.2 mm finish line offset, 0.5 mm thickness) combined with FS.   132   Figure 5-14 Estimated marginal means of Linear measure for each combination of sintering within a group at each stage and their respective 95% confidence intervals. mm 133   Figure 5-15 Estimated pairwise stage difference in Linear Measure and their respective 95% confidence intervals. mm 134   Figure 5-16 Estimated pairwise stage differences in Linear measure for each combination of group and sintering and their respective 95% confidence intervals. mm 135  5.3.2 Secondary Outcome: Interaction Between Coping Design (Group), Sintering (Sintering) and Processing Stage (Stage) on Volumetric Measurements (VM) The median values of the VM for each combination of Group, Sintering and Stage with the entire distribution of observation per each combination are presented in Figure 5-17. The combination of G1 (0.5 mm finish line offset, 0.5 mm thickness) with SS and G5 (1.2 mm finish line offset and 1.0 mm coping thickness) with FS resulted in the smallest volumetric differences between Stages 0 and 2. On the other hand, the combination of G3 (0.5 mm finish line offset, 1.5 mm thickness) with FS resulted in the largest volumetric differences between Stages 0 and 2.    Figure 5-17 Volume by Group, Sintering and Stage.  The mean values of VM for each combination and the crossing lines in the graph indicate the possible presence of interaction between Group, Sintering and Stage presented in Figure 5-18. mm3 136  There was no mean difference between the sintering methods at Stage 2. G3 (0.5 mm finish line offset, 1.5 mm thickness) resulted in the largest volume differences between Stages 0 and 2 for both sintering methods.  Figure 5-18 Interaction plot of Volume measure by Group  Sintering  Stage. Interaction plot for effect of Group  Stage on Volume. Points on the plot represent mean values of the VM for each combination of Group  Stage. Dotted lines represent standard errors of the respective mean estimates. SS and FS are parallel except at G4.      mm3 137  Table 5-6. Descriptive table of the average percentage change between each of the stages for each combination of the Group and Sintering. Columns Vol_St0,Vol_St1,Vol_St2 correspond to average Volume for each stage, and for each combination of Group and Sintering. Stages Group sin Vol_St0 mm3 Vol_St1 mm3 Vol_St2 mm3 Percentage Change % 0--1 1 FS 107.50 213.95 NA 99.02 0--1 1 SS 107.50 208.64 NA 94.08 0--1 2 FS 208.48 372.55 NA 78.70 0--1 2 SS 208.48 372.11 NA 78.49 0--1 3 FS 342.87 606.48 NA 76.88 0--1 3 SS 342.87 618.64 NA 80.43 0--1 4 FS 119.99 189.14 NA 57.63 0--1 4 SS 119.99 209.86 NA 74.90 0--1 5 FS 230.96 451.46 NA 95.47 0--1 5 SS 230.96 436.83 NA 89.14 0--1 6 FS 385.84 743.68 NA 92.74 0--1 6 SS 385.84 737.62 NA 91.17 1--2 1 FS NA 213.95 104.18 -51.31 1--2 1 SS NA 208.64 105.47 -49.45 1--2 2 FS NA 372.55 199.94 -46.33 1--2 2 SS NA 372.11 200.92 -46.01 1--2 3 FS NA 606.48 312.92 -48.40 138  1--2 3 SS NA 618.64 318.21 -48.56 1--2 4 FS NA 189.14 111.18 -41.22 1--2 4 SS NA 209.86 112.47 -46.41 1--2 5 FS NA 451.46 232.52 -48.50 1--2 5 SS NA 436.83 224.14 -48.69 1--2 6 FS NA 743.68 382.51 -48.57 1--2 6 SS NA 737.62 383.08 -48.07 2--1 1 FS NA 213.95 104.18 105.37 2--1 1 SS NA 208.64 105.47 97.82 2--1 2 FS NA 372.55 199.94 86.33 2--1 2 SS NA 372.11 200.92 85.20 2--1 3 FS NA 606.48 312.92 93.81 2--1 3 SS NA 618.64 318.21 94.41 2--1 4 FS NA 189.14 111.18 70.12 2--1 4 SS NA 209.86 112.47 86.59 2--1 5 FS NA 451.46 232.52 94.16 2--1 5 SS NA 436.83 224.14 94.90 2--1 6 FS NA 743.68 382.51 94.42 2--1 6 SS NA 737.62 383.08 92.55 0--2 1 FS 107.50 NA 104.18 -3.09 0--2 1 SS 107.50 NA 105.47 -1.89 139  0--2 2 FS 208.48 NA 199.94 -4.10 0--2 2 SS 208.48 NA 200.92 -3.63 0--2 3 FS 342.87 NA 312.92 -8.73 0--2 3 SS 342.87 NA 318.21 -7.19 0--2 4 FS 119.99 NA 111.18 -7.34 0--2 4 SS 119.99 NA 112.47 -6.27 0--2 5 FS 230.96 NA 232.52 0.68 0--2 5 SS 230.96 NA 224.14 -2.95 0--2 6 FS 385.84 NA 382.51 -0.86 0--2 6 SS 385.84 NA 383.08 -0.72 2--0 1 FS 107.5 NA 104.18 3.19 2--0 1 SS 107.5 NA 105.47 1.92 2--0 2 FS 208.48 NA 199.94 4.27 2--0 2 SS 208.48 NA 200.92 3.76 2--0 3 FS 342.87 NA 312.92 9.57 2--0 3 SS 342.87 NA 318.21 7.75 2--0 4 FS 119.99 NA 111.18 7.92 2--0 4 SS 119.99 NA 112.47 6.69 2--0 5 FS 230.96 NA 232.52 -0.67 2--0 5 SS 230.96 NA 224.14 3.04 2--0 6 FS 385.84 NA 382.51 0.87 140  2--0 6 SS 385.84 NA 383.08 0.72 Vol: Volume, St0: Design Stage,_St1: Milling Stage, St2: Sintering Stage  Table 5-7. Descriptive table of the average percentage change between each of the stages for each Sintering method averaged over the 6 Groups. Columns Vol_St0,Vol_St1,Vol_St2 correspond to average Volume for each stage, grouped by sintering method while taking average over the 6 groups. Stages sin Vol_St0 mm3 Vol_St1 mm3 Vol_St2 mm3 Percentage Change % 0--1 FS 232.61 429.54 NA 84.67 0--1 SS 232.61 430.61 NA 85.13 1--2 FS NA 429.54 223.88 -47.88 1--2 SS NA 430.61 224.05 -47.97 2--1 FS NA 429.54 223.88 91.87 2--1 SS NA 430.61 224.05 92.20 0--2 FS 232.61 NA 223.88 -3.75 0--2 SS 232.61 NA 224.05 -3.68 2--0 FS 232.61 NA 223.88 3.90 2--0 SS 232.61 NA 224.05 3.82 Vol: Volume, St0: Design Stage, St1: Milling Stage, St2: Sintering Stage  Figures 5-17 and 5-18 and Tables 5-6 and 5-7 indicated that the average percentage enlargement between stage 0 (design) and 1 (milling) were 85.13 % within SS and 84.67 % within FS. The average volumetric values of the final, sintered specimens were reduced, in average 47.97 % within SS and 47.88 % within FS upon sintering. In another word, the volumetric percentage 141  changes between stage 2 and 1 were in average 92.20 % within SS and 91.87 % within FS upon sintering. In general, the final crowns (Stage 2) were in average 3.82 % smaller when sintered by SS; and 3.90 % smaller when sintered by FS than the original design. The significance of interaction between Group, Stage and Sintering was tested by linear mixed effect model. An ANOVA Type 3 table for the three-way interaction Group x Sintering × Stage estimated from the linear model was significant (F value= 2.716; p <0.001) (Tables 5-8 and 5-9). The model is specified with Volume as response and the three-way interaction of interest, Stage  Group  Sintering; three two-way interactions, Stage  Group, Stage  Sintering and Group  Sintering; main effects for Stage, Group and Sintering and random effect for the Sample to account for the correlated observations within a Sample. Therefore, since the three-way interaction was significant, the model was used to estimate the mean VM and its 95%CI for each combination in the tested three-way interaction. Within Stage 2, the mean Volume estimate for SS was slightly higher than FS except at G5 (Figure 5-19). There was no observed significant difference between stages 0 and 2 or between sintering methods individually.        142  Table 5-8 ANOVA Type 3 table to test the significance of the three-way interaction from the linear mixed effect model. The model is specified with Volume as response and the three-way interaction of interest Stage  Group  Sintering, three two-way interactions Stage  Group, Stage  Sintering and Group  Sintering, main effects for Stage, Group and Sintering and random effect for the Sample to account for the correlated observations within a Sample                  143  Table 5-9 Estimated coefficients for the three-way interaction, three two-way interactions and main effects from the linear model mixed effect model specified in Table 5-4.    144   Figure 5-19 Estimated mean Volume by Group  Sintering  Stage interaction from the model.  Similar to the analysis for the Linear measure, comparisons were performed: i) between FS and SS within each Group at each Stage and ii) between the three stages for each combination of Group and Sintering (Figures 5-20, 5-21, and 5-22). P-values for comparisons of Sintering methods within Group and Sintering were not adjusted, while the p-values for the pairwise mm3 145  comparisons of Stage for each combination of Group and Sintering were adjusted for three tests using False Discovery Rate (FDR). At Stage 2, there was no significant difference between SS and FS in each of the groups. Significant differences between Stage 0 and Stage 2 were found only for G3 (0.5 mm finish line offset, 1.5 mm thickness), in both FS and SS, and for G4 (1.2 mm finish line offset, 0.5 mm thickness) with FS. This means that significant volumetric discrepancies between the design and the milled, fully sintered prosthesis were observed when the design is 0.5 mm finish line offset, 1.5 mm thickness or 1.2 mm finish line offset, 0.5 mm thickness, combined with FS.  Figure 5-20 Estimated marginal means of Volume for each combination of sintering within a group at each stage and their respective 95% confidence intervals. mm3 146    Figure 5-21 Estimated pairwise stage difference in Volume and their respective 95% confidence intervals.  mm3 147   Figure 5-22 Estimated pairwise stage differences in Volume for each combination of group and sintering and their respective 95% confidence intervals.  mm3 148  5.4 Discussion  The results of this study revealed a significant interaction between different coping designs and sintering protocols on the linear and volumetric dimensions of zirconia copings. Therefore, the null hypothesis was rejected. The average percentage increases in linear dimension between designing stage (Stage 0) to the milling stage (Stage 1) was about 22 %, which is generally corresponds to what was predicted by the manufacturer (Tables 5-2 and 5-3). However, the linear percentage changes between stage 2 and 1 were in average 23 % upon sintering. The linear percentage differences between the final, sintered specimens were, in average 1.32 % within SS and 1.54 % within FS, smaller than the original design for all the groups. This indicates that discrepancies in the adaptation were to be expected. The average percentage increases in the volumetric dimensions of the milled samples between designing stage (Stage 0) and milling stage (Stage 1) was about 85 % (Tables 5-4 and 5-5). The volumetric percentage changes between stage 2 and 1 were in average 92 % upon sintering. In general, the final crowns (Stage 2) were in average 3.82 % smaller when sintered by SS; and 3.90 % smaller when sintered by FS than the original design. This also indicates that discrepancies in the adaptation were to be expected. Our findings showed that the combination of G1 (0.5 mm finish line offset and 0.5 coping thickness) and SS presented with reduced percentage changes between the designing and milling stages in both linear and volumetric measurements. This finding implies that a coping design such as G1 would be a preferable choice when designing the crown, to result in fewer discrepancies between the virtual design and final crown, regardless of the two sintering protocols used in this study.   Because the data were balanced between the groups, a linear mixed model was the selected statistical analysis to measure the changes at the three processing stages. Our findings indicated 149  that there were significant differences between the three stages of zirconia processing in all possible combinations in linear measurements. Thus, the amount of increase during the milling stage is unequal to the amount of sintering shrinkage. This amount is shown to be altered according to the coping design and sintering protocol. We hypothesize that such different degrees of shrinkage at different locations and designs of the coping could be compensated for at the milling, Stage 1. Further research is needed to confirm/reject this hypothesis. Within Stage 2 (after sintering), our findings indicated no significant differences were resultant from the two selected sintering protocols, except for linear measurements in G4 (1.2mm finish line offset, 0.5 coping thickness, p value= 0.025). There was no statistically significant difference between FS and SS in volume change between stages 0 and 2. The significant level of the dimensional differences observed in G4 at Stage 2 (sintering) between both SS and FS sintering protocols in the linear measurements can be attributed to the tolerance range of the scanning device and the software accuracy, as well as the differences in zirconia microstructures between different blanks. Based on analysis of the measurements results for Stage 1 (Figure 5-11), the errors due to tolerance range of equipment were estimated to be in the range of 30-40 m. Thus, any significance differences between tested variables within this range should not be considered a true value.  Our findings indicated that the smallest significant difference between the baseline and the sintered stages was at the combination of G1 (0.5 mm finish line offset, 0.5 mm coping thickness) with SS and G6 (1.2 finish line offset, 1.5 coping thickness) with SS in the linear measurements compared to all other SS combinations. G1 (0.5 mm finish line offset, 0.5 mm coping thickness) had also the smallest significant difference between the baseline and the sintered stages among FS combinations. We hypothesize that thicker coping had lower resistance to creep at the higher temperature of FS cycle. On the other hand, in the volumetric analysis, the level of significant 150  difference was highest significantly between the baseline and the sintered stages for G3 (0.5 mm finish line offset, 1.5 coping thickness) when sintered by FS and SS compared to all other combinations. The complex 3D shape of the crowns did not allow any further quantitative analysis of the combined effects of gravitational stress and creep rate due to temperature changes at different locations on the coping in this work. Therefore, Finite Elements Method could deal with this complex analysis by more precisely correlating between coping distortion in different locations and the sintering parameters. The accuracy and precision of intraoral scanners has been well documented in the literature [163]. 3shape Trios scanner has a reported scanning accuracy of 6.9 +/- 0.9 m and trueness of 4.5 +/- 0.9 m [158]. Utilizing this technique has provided .stl files from the scanning of the 3D object at the milling and sintering stages in a real dimension and allowed them to be compared to the coping original design on the digital software in the same .stl format. On the other hand, the accuracy of Meshmixer to perform both linear and volumetric measurements is not documented in the literature. Therefore, validation steps had to be performed by using a digital caliper for linear measurements and ImageJ software for volumetric measurement to be able to estimate the error and validate the technique.  A recently published study compared the 3D dimensional changes of implant-supported crowns before and after adjustments by superimposing the two .stl files obtained from intraoral scanning and exporting them into Geomagic 2014 software to obtain “Best fit alignment” [164]. This technique could be used in our study for comparison between the design and sintered dimensions, but could not be used between the design and milling stages and/or the milling and sintering stages because the enlargement factor during the milling process does not provide appropriate landmarks for superimposition. Therefore, the linear and volumetric measurements in 151  this study were obtained in a real dimension [mm and mm3, respectively] and comparative analyses were done without superimposing .stl files.  Regardless of the sintering protocol used in this study, all groups (coping designs) resulted in linear and volumetric measurements at the sintered stage (Stage 2) that were smaller compared to the corresponding group at the baseline designing stage (Stage 0), thus resulting in milled crowns that were 3-dimensionally smaller than the virtual design. This could be related to zirconia behavior during sintering, leading to the conclusion that the final dimensions of the definitive prosthesis, regardless of the sintering protocol used, are not the same as the dimensions anticipated during the designing stage. However, coping design with 0.5 mm finish line offset and thickness of 0.5mm had smaller dimensional changes linearly and volumetrically compared to the other designs. Including the cement thickness parameter in the design permits the definitive prosthesis to fully seat on the prepared tooth without the need to adjust the intaglio surface. Another suggestion is to enlarge the design by a factor during the design stage of the prosthesis to account for the linear and volumetric shrinkage value that is expected to result in prostheses that are slightly smaller than the original designed sample. From the findings of this study, crowns should be designed ~3% larger to compensate for the average -3% discrepancy encountered after sintering, regardless of the sintering method used. As our knowledge progresses on the behavior of zirconia copings during the sintering process, the “design enlargement factor” could be further customized to the particular coping design and particular location on the coping.   The results cannot be generalized to all zirconia brands, as only one type of zirconia was tested in this study. The creep deformation rates of other zirconia might be different from the one used in this study due to differences in the amount of impurities as well as the zirconia phase. Finally, detaching the zirconia from the zirconia blanks after milling (before sintering) was done 152  by hand. While all efforts were made to always have the same operator for this procedure and the use of magnification to avoid errors, this could have affected the volumetric measurements between samples. In the future, more comprehensive studies are needed to overcome these limitations and to investigate the effects of the position of different types of zirconia prostheses inside the sintering oven, on the sintering protocols, and on the sintering shrinkage and marginal adaptation. 5.5  Conclusions There was a significant interaction between the coping design, processing stage and sintering protocol on linear and volumetric dimensional changes. G1 coping design (0.5 mm finish line offset, 0.5 mm thickness) processed in Standard Sintering protocol (SS) showed the least linear and volumetric dimensional changes among the groups. Sintered copings had shrunk in an average of 1.32 % within SS and 1.54 % within FS linearly and 3.82 % within SS and 3.90 % within FS volumetrically compared to the initial design parameters. Standard sintering had lower volumetric shrinkage between the designing and sintering stages compared to the fast sintering protocol.   153  Chapter 6: Summary and Conclusion The combined research projects involved in this study delivered insight into and predictions of essential factors that influence the adaptation of the dental prosthesis to tooth structure, namely the dimensional changes of the material during processing. Zirconia processing begins with data acquisition via conventional or digital impressions of the preparation design, designing the prosthesis virtually on the software after determining the cement space, milling the prosthesis in an enlarged form to compensate for the sintering shrinkage and finally sintering the prosthesis to achieve proper geometry and full density and strength. The accuracy and precision of the definitive prosthesis fabrication is an accumulated outcome of the effects of each of the previous steps.  Studying the effect of altering preparation designs (first step) and sintering protocols (final step) on the dimensional changes of zirconia during processing stages and/or marginal adaptation provided knowledge and insights for dental clinicians about the optimum preparation design that should be considered when preparing teeth for full contoured zirconia crowns or copings. It also deepened dental clinicians’ and laboratory technicians’ knowledge about the effects of using different sintering protocols, either standard or fast, on the final seating of the crowns on the tooth structure.  There is heterogeneity in literature regarding which specimen preparation design should be applied when testing a clinically-relevant characteristic outcome of zirconia material, as in this case there are marginal and dimensional change discrepancies. Some of the studies have used machined cylindrical-shaped metal master dies [59, 110, 122, 125, 165]. Other studies have used manually prepared extracted teeth [57, 60, 119, 166],  acrylic model teeth [58] or implant-abutment anterior teeth [114]. Moreover, in accordance with the currently available principles of full-154  ceramic restorations, the amount of tooth reduction is more for full-ceramic restorations than for metal-ceramic restorations due to the necessity for a uniform 1.0 mm wide chamfer or rounder shoulder margin design to allow for an even thickness and adequate strength. The shoulder or chamfer should be rounded internally to reduce stresses within the tooth and ceramic [167]. The margin design of a deep chamfer finish line is recommended by most zirconia manufacturers. However, some manufacturers claim that rounded shoulders as well as feather-edge finish lines are suitable for zirconia full-coverage restorations. The occlusal convergence of the preparation design is one of the major factors influencing the marginal precision of the final prosthesis [168]. The total occlusal convergence of the axial walls of 12° allowed the reduction of the superstructure vertical gap of single crowns (46-50 μm) with respect to angles of 4° (67-91 μm) and 8° (67-82 μm). Our systematic review maps almost all the factors in the dental literature that may affect the adaptation and fit of zirconia crowns.   Regarding the preparation design, the use of a standardized cylindrical- or square-shaped machined master die with different design configurations provided standardized preparations for direct comparison of discrepancies. However, this has the limitation of making the preparation unrealistic and non-simulated to the clinical situation and therefore, clinical extrapolation of the results can be difficult. On the other hand, a simulated clinical scenario using master dies prepared manually by one dentist may provide the study with a simulated clinical scenario but it will lack precise standardization and thus will make controlling variability during testing difficult as well. Even if we had used putty index, surveyor and microscope to assess the final characteristics of the preparation, they would still lack the standardization of uniform marginal finish line thickness and precise angle of convergence. Therefore, in our studies, implant abutments from Astra core file were used to obtain standardization and simulate the clinical scenario of tooth preparation. The 155  reason for choosing titanium master dies is that they exhibit a radio-optical property and also do not wear from repetitive seating of crowns during assessment. Additionally, the Atlantis core file allowed us to bypass the step of taking impressions either digitally or conventionally, thus preventing these other confounding factors from influencing the results.   Different sintering parameters may show a strong influence on the mechanical, optical and dimensional properties of the zirconia prosthesis. From clinical and economical points of view, shorter sintering time would be beneficial for a faster manufacturing process for zirconia prostheses. However, our systematic review confirmed the fact that altering sintering protocol altered the mechanical, physical or optical properties of zirconia. To the authors’ best knowledge, this is the first published study focusing on testing altering sintering protocols on the dimensional changes and marginal adaptation of monolithic zirconia crowns and/or copings. They confirmed the significant interaction between the preparation, design, and sintering protocols. In the marginal fit experimental study, it was found that a 1.0 mm finish line yielded consistent marginal adaptation results under both sintering protocols and using both crown thicknesses of 0.8 mm and 1.5 mm. However, a 0.5 mm finish line had better marginal adaptation, with minimal occlusal reduction under fast sintering protocols, but yielded inconsistent results when used with thick crowns. Therefore, our recommendation is to use 0.8-1.0 mm finish line preparation whenever the occlusal reduction is more than 0.8 mm. A 0.5 mm finish line can be used with conservative occlusal reductions <0.8 mm.  The technique used to measure the linear and volumetric changes of zirconia materials at the three stages of processing is unique and can be further used in dental materials research to assess the dimensional changes of the materials after scanning the 3D object with an intra-oral scanner. Dental clinicians and technicians always assume that the degree of enlargement of 156  zirconia prostheses during milling is exactly equal to the degree of sintering shrinkage when applying the blank barcode details to the milling machine. Within the limitations of our studies, it was found that the degree of enlargements during milling was lower than the degree of sintering shrinkage in both sintering protocols and this in turn could lead to zirconia distortion. Consequently, there will be a need to adjust the prosthesis to attain full seating before cementation. Adjusting zirconia leads to flaws in the microstructure that induce phase transformation and can result in future aging and phase transformation of zirconia structures.  The mechanism of deformation in ceramics occurs either by dislocation motion or by grain boundary sliding [169]. In nanoceramics of a grain size above ~100 nm, the main deformation mechanism is derived by dislocation motion, while for ultra-fine nano grain sizes (< 50 nm) the deformation mechanism is derived by grain boundary sliding [169]. The possible mechanism that could explain the observed distortion of zirconia material at 1520ºC and very low stress would likely be slow diffusional creep. Creep deformation is time-dependent permanent deformation that is often due to diffusion process than dislocation motion [19]. Diffusion along zirconia grain boundaries causes mass redistribution of yttria leading to distortions. Yttria-stabilized zirconia (YSZ) exhibits superplastic strain rate 34 times faster than sub-micrometer grained YSZ when measured at the same temperature [169]. Dominguez-Rodrigues et al. explained the superplasticity mechanism of pure Y-TZP over all the ranges of temperatures, stress, grain sizes and surrounding atmosphere by grain boundary sliding accommodated by diffusional [170]. In their study the stresses were generally more than 10 MPa, whereas, in our studies, we likely had stresses less than 0.1 MPa. Although no meaningful deformation model data can be generated at very low stress, yet these deformations could be still large enough to distort the zirconia crowns  157  Practically and within the limitations of our studies, the linear and volumetric dimensional changes did not differ significantly between standard and fast sintering protocols, and the preparation designs had more influence on the marginal adaptation and dimensional changes compared to sintering protocols.  6.1 Limitations Limitations of the current studies and the possible solutions to circumventing these limitations are discussed below: 1- We were not able to obtain samples of fully-sintered zirconia crowns to use as a control group because of the difficulty of the “hard-mill” technique. The hard-mill technique increased the expense due to attrition of milling tools and it is also a time-consuming process. No dental laboratories available offered such a hard-milling method. 2- All crowns were fabricated under close to optimum conditions for standardization purposes and to decrease the number of possible confounding factors. However, this might not reflect the daily clinical practice.  3- In our study, we focused on measuring the vertical marginal gap and did not measure the absolute marginal gap, which is considered the best alternative estimation of the marginal gap, since it reflects the total crown misfit (vertically and horizontally). This was not done because it would require the destruction of the crown. 4- The results cannot be generalized to all zirconia brands, as only one type of zirconia was tested in this study.  5- Marginal gap measurements were obtained without cementation, but the cementation is known to increase the marginal gap. Comparing the results before and after cementation will make them more clinically applicable. We did not cement the crowns to allow for 158  further studies to be conducted with the crowns, i.e., fatigue resistance and reliability upon stress testing. 6- The experimental studies were limited only to two sintering protocols and should not be applicable to other existing or upcoming sintering protocols.    6.2 Future Directions 1- For these projects, we envision expanding our research in evaluating fracture and fatigue resistance of monolithic zirconia crowns under the influence of different preparation designs, with or without the aging process. Therefore, the effect of low thermal degradation (LTD) could be assessed under different sintering protocols.  2- Future studies should analyze the grain size and phase content after different sintering protocols.  3- Wear, color and strength could be compared between crowns sintered by standard recommended protocols and those using fast sintering protocols.  4- Due to advancement of chair-side technology, zirconia manufacturing companies are moving toward using the ultra-fast sintering protocol, which is 30 min in total compared to the fast sintering protocol used in this study, which is around 2-3 hours total. Further studies should test the effects of the ultra-fast sintering protocol on dimensional changes as well as marginal adaptation, color stability and the aging process.  5- Furthermore, alternative methods can be proposed to assess the 3D crown distortion via superimposition techniques performed using a highly sophisticated software methodology [129, 171, 172].  159  6- Further dimensional change studies with larger sample size and more precise measurement techniques should be done to reduce errors of volumetric and linear measurements and provide us with more confidence in the effects of the different sintering techniques. 7- Clinical studies are needed to support the use of high speed sintered zirconia prostheses for long-term performance.   160  References  1. Suttor, D., et al. LAVA--the system for all-ceramic ZrO2 crown and bridge frameworks. Int J Comput Dent. 2001; 4(3): 195-206. 2. Besimo, C.E., H.P. Spielmann, and H.P. Rohner. 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Effects of using different sintering techniques and various Zr thicknesses on “Optical Properties”  Square specimens 22  22 mm  Sintering: L* (SD) a* (SD) b* (SD) TP (SD) ∆E00 Vm Conventional/0.5 Conventional/1.0 Conventional/1.5 Microwave/0.5 Microwave/1.0 Microwave/1.5 A2 shade tab 72.15 (.73) 69.44 (.44) 68.9 (1.05) 72.60 (.32) 70.36 (.71) 68.57 (.34) 60.27 (.01) -1.81 (.09) -1.37 (.09) -1.20 (.07) -1.65 (.09) -0.99 (.17) -0.93 (.17) -0.20 (.01) 14.81 (.53) 15.41 (.36) 14.33 (.33) 15.35 (.50) 16.10 (.79) 15.07 (.48) 11.95 (.01) 11.52 (.15) 7.87 (.13) 5.31 (.20) 11.43 (.15) 7.50 (.11) 5.28 (.12) 9.97 7.97 7.39 10.32 8.69 7.20  11.63 9.02 12.58 10.56 9.37 11.69 Kaizer et al.  Effects of speed sintering on optical, mechanical, and wear characterization  inCoris monolithic molar crown Factor G.S TP (SD) VH (SD) F.S[43] Wear D Wear V LT 0.66 4.3 (.4) 13.3 (.1) 579 (130.6) 0.76 (.7-.81) 1.12 (1.05-1.2) S 0.5 4.2 (.5) 13.1 (.2) 622 (82.1) 0.63 (.62-.65) 1.42 (1.25-1.58) SS 0.59 4.6 (.4) 13.1 (.2) 904.27 (115.7) 1.04 (.93-1.14) 1.86 (1.58-2.15) Sulaiman et al.  Effects of staining & vacuum sintering on the optical and Group  TP CR ∆E* F.S 178  mechanical properties of PSZ & FSZ  Disc zirconia samples PSZ stain 9.7 0.92 8.6 1100 Stained 9.5 0.94 9.2 1000 Vacuum 10.9  8 1220 FSZ stain 13.4 0.87 7.8 700 Stained 12 0.9 9.2 1000 Vacuum 12.5  8 850 Ersoy et al.  The effects of sintering t/T on the flexural strength & G.S. of Zr Bar specimen 1.2X4X25 mm 3YTZP 2 zirconia materials In-Coris ZI & In-Coris TZI Group F.S G.S Standard ZI Speed ZI Superspeed ZI Standard TZI Speed TZI Superspeed TZI 700.3 (125.3) 662.1 (77.8) 871.8 (108.8) 579.7 (140.6) 622.3 (82.7) 9.4.2 (115.7) No quantitative analysis was performed for the G.S., and the surface composition t→ m was not analyzed.  Ebeid et al.  Group F.S CR Ra G.S ∆E HVN 179  Effects of changing sintering parameters on color, translucency, flexural strength Disc 15 mm in diameter 1460C /1 hr 1530C /2 hr 1600C /4 hr 1460C /1 hr 1530C/2 hr 1600C /4 hr 1460C /1 hr 1530C /2 hr 1600C /4 hr 1000 975 925 900 950 925 970 950 970 0.75 (.02) 0.72 (.01) 0.71 (.01) 0.75 (.03) 0.71 (.01) 0.70 (.01) 0.71 (.01) 0.69 (.01) 0.68 (.01) 1.023 (.19) 1.026 (.30) 0.898 (.19) 1.023 (.16) 0.878 (.21) 0.957 (.24) 0.991 (.19) 1.069 (.08) 0.826 (.16) 0.55 (.1) 0.65 (.13) 0.89 (.19) 0.64 (.11) 0.77 (.13) 1.0 (.11) 0.79 (.15) 0.92 (.25) 0.92 (.14) 4.4 (.3) 3.1 (.1) 2.4 (.1) 4.0 (.1) 2.8 (.3) 2.2 (.1) 3.8 (.1) 2.9 (.1) 2.2 (.1) 1456 (212) 1553 (111) 1461 (108) 1504 (123) 1548 (77) 1507 (71) 1497 (138) 1437 (74) 1415 (60)  Inokoshi et al.  Effects of sintering conditions on LTD In-CeramYZ Higher sintering temperatures and times increased zirconia grain size, led to decreased yttrium content in the remaining tetragonal grains and made the samples having a higher monoclinic phase more susceptible to LTD.   Kim et al.  Group MS C20 C2h  C10h C40h 180  Effects of sintering time on grain size and translucency 10X10X 1 mm Lava frame zirconia Kavo Everest ZS-blanks Lava TP Kavo TO Lava G.S Kavo G.S 34.48 (.24) 30.50 (.37) 347 (26) 373 (18) 30.32 (.64) 29.62 (.20) 477 (17) 415 (45) 29.80 (.32) 28.62 (.31) 603 (40) 605 (70) 28.86 (.16) 28.39 (.43) 735 (84)91 912 (58) 28.39 (.19) 28.09 (.37) 1512 (172) 1481 (149) Stawarczyk et al.  The effects of different sintering temperatures on flexural strength, contrast ratio, and grain size Ceramill ZI  Sintering CR F.S Weibull 1300C 1350C 1400C 1450C 1500C 1600C 1650C 1700C 0.58 (0.01) 0.81 (0.01) 0.78 (0.01) 0.77 (0.01) 0.77 (0.02) 0.75 (0.01) 0.74 (0.01) 0.70 (0.01) 0.68 (0.01) 969.8 (157) 950.9 (201) 1119.3 (143) 1214.5 (194) 1281.1 (230) 1256.7 (165) 979.2 (218) 856.4 (168) 585.6 (251) 6.6 4.8 8.4 6.7 5.9 8.1 5.0 5.1 2.1 Almazdi et al.  Comparison of surface quality, mechanical & physical properties between furnace and microwave methods (YTZP Emax ZirCAD) Flexural strength C 1080.08 (79.37) and MS 1108.33 (162.55) Density C 99.9 (0.22), MS 99.9 (0.16) Porosity size was smaller in MS MS uniform G.S. distribution 181  Jiang et al.  Effects of sintering temp. and particle size on Zr translucency YPSZ discs Particle size Sintering TC Transmittance % 40 nm 1350C 1400C 1450C 1500C 15.51 (0.58) 17.50 (0.47) 17.83 (0.16) 18.01 (0.07) 90 nm 1350C 1400C 1450C 1500C 1.76 (0.06) 8.82 (0.58) 16.98 (0.38) 17.58 (0.1) Hjerppe et al.  Effects of sintering time on flexural strength ICE Zirkon Disc  t/T F.S (Dry) F.S (Tc-20000) 1:40+1 h 1096.6 1057.7 3 h+2 h 1074.7 1127.1 Zr, zirconia; PSZ, partially sintered zirconia; FSZ, fully sintered zirconia; CIELab (L* a* b*), color coordinates; TP, translucency; ∆E00, CIEDE2000 color differences; Vm, monoclinic volume content (%); F.S, flexural strength; YTZP, yttria-stabilized tetragonal zirconia polycrystalline; MS, microwave; CR, contrast ration; LT, long term; S, speed; SS, superspeed; HVN, Vickers hardness evaluation; ∆E, color difference; Ra, roughness, G.S., grain size (); SD, standard deviation; t/T, sintering time/Temperature; wear D, wear depth (mm); wear V, wear volume mm3; h, hour (s); Tc, thermocycling; , increase;  decrease; T, temperature  

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