Bone tissue engineering on biodegradable polymers

grantor: University of TorontoThis thesis presents work on the use of biodegradable, biocompatible polyesters for bone tissue engineering applications. New processing routes to create open-cell foam structures using polyesters were developed. The design of these new foams was based on the morphology of trabecular bone. Highly interconnected pores in the millimeter range or larger, were created and bone cell growth and differentiation within these structures were investigated. To identify an appropriate biocompatible, biodegradable polymer, initial studies investigated poly(lactide-co-glycolide)s (PLGA)s with different ratios of lactide:glycolide as thin films. Bone marrow cell differentiation and matrix elaboration on the polymer surfaces were monitored by tetracycline staining. It was demonstrated that PLGA 75/25 was the best substrate for cell proliferation and matrix formation of the biodegradable polymers investigated. PLGA 75/25 was then used to prepare 3-D open-cell foam structures similar to the isotropic regions of trabecular bone. A new foaming protocol, namely a phase-inversion particulate-leaching process, was developed. New foam structures were created and characterized for pore size, pore wall thickness, pore interconnectivity and mechanical behaviour. A degradation study of the new foam structures was conducted. PLGA 75/25 foams, degraded at pH 5.0, 6.4 or 7.4, maintained their 3-D morphology for at least 4.5 months. This result indicated that the rate of foam degradation ' in vitro' is likely slower than that of bone formation 'in vivo'. Bone marrow cells differentiated into osteoblasts and grew throughout the 3-D foams. The effect of different foam morphologies on cell colonization of the scaffolds was studied and the morphological requirements for a 3-D structure to serve as a scaffold for bone tissue engineering were established. Future work includes research on bone growth throughout the foam structures ' in vivo'. Preliminary 'in vivo' results indicate that new tissue formed throughout the entire foam structures retrieved from the rat femora.Ph.D