UBC Theses and Dissertations
Calcium phosphate silicate cement for risedronate drug delivery Gong, Tianxing
The effectiveness of bone cements in treating bone fracture is impaired by osteoporosis, which not only delays the osseointegration but also compromises the stability of implants. As a result, further fractures are not unusual after bone cement implantation in osteoporotic patients. This dissertation reports the investigation of the novel calcium phosphate silicate cement (CPSC) as a possible drug delivery system (DDS) for risedronate (RA) to treat osteoporosis and to restore bone fracture. Risedronate belongs to the family of bisphosphonate and, as the 3rd generation of bisphosphonate, can effectively suppress osteoclast activities and treat osteoporosis. In this work, the CPSC material properties were characterized as a function of RA content. High performance liquid chromatography was used to detect RA release profiles from cements and the Higuchi’s Law was employed to explain its release mechanisms. In vitro biocompatibility of RA-added CPSC (CPSC-R) was evaluated by MTT assays, flow cytometry, and real-time polymerase chain reaction. In the tibia implantation model from osteoporotic rabbits, biomarkers, X-rays, computed tomography, histology and PCR arrays were used to evaluate CPSC-R in vivo performance. It has been found that RA greatly affected CPSC setting time and compressive strength in a concentration-dependent manner. It was also found that RA disrupted CPSC hydration and delayed calcium silicate hydrate gel formation. RA was progressively adsorbed onto the unreacted calcium silicate and formed calcium-RA complexes. RA release kinetics from cement was controlled by the implant degradation and was in a good agreement with the theoretical calculations. CPSC-R was biocompatible and improved osteoblast proliferation and differentiation. Biomarker studies showed that CPSC-R significantly reduced osteoclast activities as compared to the sham control (p < 0.05). The radiographic and histological examination demonstrated that CPSC-R improved osseointegration and bone formation, as compared to RA-free CPSC control group. Gene array studies indicated that CPSC-R implants could significantly up-regulate osteogenesis-related gene expressions as compared to the control groups. In conclusion, this study indicates that CPSC is potentially a good Drug Delivery System of RA. The anti-osteoporotic effectiveness of this system could be beneficial in bone fracture treatments for patients who are suffering from osteoporosis.
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