The objective of this Fast Track SBIR proposal is to test the hypothesis that a synthetic peptide which binds to a cell surface receptor for thrombin can initiate mitogenic, angiogenic and chemotactic signals that can stimulate native cellular mechanisms involved in bone healing. Preliminary work with this synthetic peptide (TP508) has demonstrated in vitro stimulation of osteoblast and marrow stromal cell proliferation and in vivo stimulation of fracture healing as determined radiographically and mechanically. The Phase I portion of this Fast Track proposal aims to test the feasibility of TP508 to stimulate healing of delayed and non-unions when delivered with a commercially available osteoconductive matrix (Collagraft7). Specifically the investigators will (1) determine dosage ranges based on TP508 incorporation and release, (2) test the efficacy of TP508 in a segmental defect model in a rabbit by radiographic mechanical and histomorphometric analyses and (3) analyze the pharmacokinetics of release and breakdown of TP508 in vivo. The objective of the Phase II portion of the proposal is to formulate a collagen/mineral matrix to optimize delivery, efficacy and ease of administration of the TP508 product.
Five specific aims are noted in the Phase II portion of the proposal which include (1) developing prototype formulations, (2) testing the formulations in vivo using a rabbit segmental bony defect model to generate dose response data, (3) test the stability of the product during sterilization and storage (4) test its biocompatibility and safety and (5) generate regulatory documents to support FDA approval for clinical trials.
Our vision is to provide a potent, cost-effective product optimally designed to accelerate the repair of hard tissue. Proposed products include an injectable formulation for hospital or emergency administration to acute fractures, an implantable matrix to promote fusion of non-unions and ultimately, TP508-coated joint replacement hardware and bioceramic implants.
