| Tissue engineering has been described as "The application of biological, chemical and engineering principles toward the repair, restoration or regeneration of living tissue using biomaterials, cells and factors alone or in combination." Musculoskeletal injuries and ailments requiring bone grafts numbers approximately 1.4 million per year in the United States. Traditionally, bone defects have been treated with biological grafts, such as bone autografts and allografts, each having their own advantages and limitations. These limitations include availability, donor site morbidity and possible disease transfer. These obstacles provided the motivation to apply the concepts of tissue engineering to bone and to develop synthetic bone graft substitutes that can repair, restore or regenerate diseased or damaged bone tissue. Presently the bone graft substitutes available provide some degree of compromise between what is ideal and what is provided. These compromises typically address either the mechanical requirements of bone or the promotion of tissue development with strategies focused on one, typically compromising the other. Developing a synthetic bone graft void of compromise was the ultimate objective beyond the work presented in this dissertation. The central hypothesis of this dissertation was that the inclusion of a highly porous nanofiber structure within the pores of sintered microspheres will elucidate and enhance the phenotype progression of preosteoblast cells through cell/scaffold interactions mediated by focal adhesion kinase signaling cascades while maintaining physicochemical characteristics suitable for bone tissue engineering applications. The composite nanofiber/microsphere scaffold demonstrated a compressive modulus and compressive strength above physiological levels found in trabecular bone, which was comparable to non-composite microsphere scaffolds. The composite nanofiber/microsphere scaffold demonstrated an increased and more desirable rate of degradation over microsphere scaffolds. The composite nanofiber/microsphere scaffold promoted activation of FAK and the osteoblast transcription factor Runx2 earlier and with greater magnitude than did the microsphere scaffolds. Osteoprogenitor cells on the composite nanofiber/microsphere scaffold illustrated improved phenotype progression as compared to those on microsphere scaffolds. Finally, the composite nanofiber/microsphere scaffold illustrated 1.8 times greater calcification as compared to the microsphere scaffolds after 21 days. These results indicate the composite nanofiber/microsphere scaffold hold great potential as a bone graft substitute. |
