The development of a photocrosslinked biomaterial for bone tissue engineering applications
Fisher, John Patrick
Mikos, Antonios G.
Doctor of Philosophy
The photocrosslinking of poly(propylene fumarate) (PPF) using the photoinitiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO) and low levels of ultraviolet light irradiation has been investigated as the basis for a bone tissue engineering scaffold. The photocrosslinking mechanism as well as the final network structure was studied, showing that a single phosphinoyl radical derived from BAPO was primarily responsible for the photoinitiated crosslinking of PPF. A technique to fabricate PPF into porous scaffolds using a photocrosslinking/porogen leaching strategy was developed, with characterization studies showing that the presence of the leachable porogen did not affect the initiation of the PPF crosslinking reaction in this system. An in vitro degradation study of both solid PPF networks and porous PPF scaffolds in phosphate buffered-saline was performed. The results indicated that porogen size and content could be selected to formulate the photocrosslinked PPF scaffolds with a degradation rate, porosity, and mechanical properties to match target values for a specific tissue defect. The soft and hard tissue response to photocrosslinked PPF scaffolds was studied, with the results indicating that the scaffolds were biocompatible within both soft and hard tissue. The ability of these photocrosslinked PPF scaffolds to act as a carrier for an adsorbed protein in order to promote bone formation was also examined. The results indicate that transforming growth factor-beta1 did induce significant bone formation in these porous PPF scaffolds. Finally, an in vivo study of the effects of a degradable biomaterial upon wound healing and bone formation within a tooth extraction socket was undertaken. The results show that the implantation of the hydrophobic and degradable PPF biomaterial did not significantly alter this process, while the negative control group, a hydrophilic, degradable biomaterial, significantly reduced bone formation. The effect of biomaterial's surface properties upon bone formation most closely parallel the fibroblastic growth factor-2 localization results, indicating its critical role in the initial phases of wound healing to facilitate later bone formation. These results indicate the great potential of photocrosslinked PPF scaffolds in bone tissue engineering applications.