Modulating the adhesive strength of blood clots by coagulation factor XIIIa-based technologies
department or school: Science, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Chan, Karen Ying Tung
issued: 2020-09-30T07:00:00Z
issued: 2019
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Trauma is the number one killer of people under the age of 45 worldwide. Hemorrhage is the second-leading cause of death after injuries to the central nervous system and constitutes more than 90% of potentially survivable injuries as reported in a military trauma study. Understanding the components and functions of the blood coagulation system has led to advances in the development of hemostatic materials. Blood clots form plugs over leaking vessels to stop bleeding. They need to be cohesive to resist fracture from the pressures of blood flow, and adhesive to stay localized to the wound site. While the adhesive properties of individual clot components have been well-characterized, the adhesive properties of the bulk clot are still poorly understood. It is unclear how clot components interact with themselves and substrates on the wound surface to mediate attachment of the clot to the wound site. In this study, we evaluated the adhesive strength of bulk blood clots. We determined which clot components were important in increasing clot adhesive strength to collagen, a common substrate found in wound tissues. We found that fibrin and FXIIIa increased clot adhesive strength in a concentration-dependent manner. Using this knowledge, we designed a formulation containing Q-PEG, a FXIIIa-crosslinkable synthetic macromer. The gelation of Q-PEG was coupled to the coagulation network through FXIIIa, allowing it to copolymerize with blood when clotting was activated. Copolymerizing Q-PEG with blood led to increased clot adhesion, particularly during fibrin-depleted or fibrinolytic conditions. This shows that clot adhesive strength is a property that can be modulated. Similar strategies, of coupling synthetic polymer formation to the coagulation cascade, may be useful for the design of novel hemostatic materials that improve the mechanical properties of blood clots to help them resist high pressure arterial hemorrhage. A broader application would be in the design of smart, stimul…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/71804
note: MODULATING THE ADHESIVE STRENGTH OF BLOOD CLOTS BY COAGULATION FACTOR XIIIA-BASED TECHNOLOGIES by Karen Ying Tung Chan B.Sc., The University of British Columbia, 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 (Genome Science and Technology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) September 2019 © Karen Ying Tung Chan, 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: Modulating the adhesive strength of blood clots by coagulation factor XIIIa-based technologies submitted by Karen Ying Tung Chan in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Genome Science and Technology Examining Committee: Dr. Christian J. Kastrup, Biochemistry and Molecular Biology Supervisor Dr. Jayachandran Kizhakkedathu, Pathology and Lab Medicine Supervisory Committee Member Dr. Boris Stoeber, Mechanical Engineering Supervisory Committee Member Dr. Hugh Kim, Dentistry University Examiner Dr. Vikramaditya G. Yadav, Chemical and Biological Engineering University Examiner iii Abstract Trauma is the number one killer of people under the age of 45 worldwide. Hemorrhage is the second-leading cause of death after injuries to the central nervous system and constitutes more than 90% of potentially survivable injuries as reported in a military trauma study. Understanding the components and functions of the blood coagulation system has led to advances in the development of hemostatic materials. Blood clots form plugs over leaking vessels to stop bleeding. They need to be cohesive to resist fracture from the pressures of blood flow, and adhesive to stay localized to the wound site. While the adhesive properties of individual clot components have been well-characterized, the adhesive properties of the bulk clot are still poorly unders…
has type: Thesis/Dissertation
date issued: 2019-11
is shown at: 10.14288/1.0381039
language: eng
degree discipline: Genome Science and Technology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/71804