The objective of this proposal is to promote the formation of durable bone tissue in critical size alveolar socket defects by the implantation of a biologically active, biodegradable polymer scaffold. Preliminary work in our laboratory has shown that osteogenesis within the healing alveolar bone of a rabbit tooth extraction socket model, a subcritical size defect, correlates with an increase in specific growth factor localizations. We plan to promote bone formation in a critical size alveolar socket defect, which does not heal naturally, by recapitulating those events observed in the healing, subcritical extraction socket defect. The key steps we plan to recapitulate are vascular growth, progenitor cell migration, and bone formation, as these events are most significant in the healing of bone tissue. This will be achieved by implanting a biodegradable poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)] based hydrogel scaffold, developed in our laboratory, that also serves as a carrier for the controlled delivery of specific growth factors. First, a biomimetic P(PF-co-EG) hydrogel scaffold will be developed to release fibroblastic growth factor-2, an early factor in wound healing and angiogenesis, during the initial stages of healing to promote vascular growth and maintenance within the defect site. Second, the scaffold will be designed to encourage progenitor cell migration into the defect site by the incorporation of an adhesive osteopontin-derived peptide selective for osteoblastic cells, while enhancing the formation of a wound healing tissue matrix by preventing soft tissue invasion. Third, the scaffold will release transforming growth factor-beta1, a potent differentiating factor, to encourage bone formation by osteoblastic differentiation of progenitor cells within the defect site. The amount of bone formation and quality of the newly formed bone will be assessed by light microscopy, histomorphometry of immunohistochemically stained sections, and micro-computed tomography analysis. This project will provide clinically valuable information regarding new tissue-inducing dental biomaterials for restoring oral function and esthetics to individuals who are afflicted with critical size alveolar socket defects.