In Vivo 2-Photon Microscopy and Collagen-Hydroxyapatite Scaffolds for Bone Tissue Engineering

Cell-based bone tissue engineering has shown encouraging results in animal models and even a few human patients. This method could supplement or replace autologous (patient-derived) bone as a bone grafting material, with less damage to existing bone. However the factors that lead to the successful healing of bone injuries by cell-based tissue engineering are poorly understood and the optimal biomaterial for this task has not yet been identified. This dissertation will present: (i) the development of a live animal imaging model to visualize the healing process in a tissue engineered implant for bone regeneration and the novel observations found therein, (ii) the development of a sterile collagen-hydroxyapatite scaffold for consistent bone formation in vivo, (iii) the comparison of different methods of cell delivery to collagen-HA scaffolds in the context of bone formation in vivo, and (iv) the development of a novel porogen method to enhance the permeability of collagen-HA scaffolds and the usefulness of permeability as a scaffold design metric indicative of success or failure in vivo. These results have deepened our understanding of cell-based bone tissue engineering, biomaterial fabrication, and biomaterial design, and should improve the efficacy and consistency of cell-based bone tissue engineering.