SBIR-STTR Award

In order to expand the clinical utility of bone replacement materials, we are proposing to develop a biodegradable bone graft extender with inductive capacity. Inductive biodegradable extenders would be useful in situations where autografts are preferable, yet the patients own bone stocks are insufficient. This SBIR Phase I project will determine the feasibility of enhancing the regeneration of skeletal tissues with an extender fashioned from the biopolymer poly(propylene glycol-co-fumaric acid) (PPF). This unsaturated polymer can be crosslinked in the presence of effervescent agents to create an osteoconductive network that can be immediately mixed with autograft prior to defect filling. In Phase I we will seek to develop polymer/bone combinations that demonstrate in vitro and in vivo durability over time, while supporting bone formation equivalent to traditional autologous bone grafting. Phase II would then address research objectives directed towards resolution of the clinical dilemma where autologous bone graft is recognized as the preferable "gold standard," but may not be available in sufficient quantities. This composite could have biological properties that are superior to the cortico-cancellous allogeneic bone chips routinely used in this situation. Osteoinductive autograft material used in conjunction with a highly osteoconductive, yet resorbable, scaffold would be attractive for both induction and expansion of new bone formation. PROPOSED COMMERCIAL APPLICATION: Bone grafts are used in over 425,000 musculoskeletal operations annually. Overall, 80% of the bone grafts are used in orthopaedic and spine surgery. Autografts are the preferred grafting material, but sometimes the patient's own bone stocks are deficient. It is estimated that synthetic bone replacement materials are used in only 25,000 - 35,000 of clinical grafting procedures because they are primarily only osteoconductive. If autogenous grafts could be easily extended via a resorbable osteoconductive material, market acceptance would follow.

In order to expand upon the clinical utility of bone replacement materials, Cambridge Scientific, Inc proposes to develop a biodegradable bone graft extender that has the ability to increase the working volume of autograft without compromising its inductive capacity of autograft Biodegradable extenders would be useful in situations in which autografts are preferable, yet the patient's own bone stocks are deficient. This grant application has as its goal the preclinical development of a degradable poly(propylene glycol-co-fumaric acid) ("PPF")-based bone graft extender containing osteoconductive hydroxylapatite fillers that can be mixed with osteoinductive cancellous autologous bone graft prior to implantation into a bony defect. In the Phase I SBIR feasibility project, Cambridge Scientific, Inc demonstrated in a small animal model that the addition of a PPF-based bone replacement material to autograft bone enhances osteointegratior of autograft which, in turn, has an effect on bony ingrowth. Following this demonstration of PPF/autograft enhancement of new bone formation, Cambridge Scientific, Inc will, in Phase II, evaluate the use of the extender material in a large animal (sheep) defect model to address the eventual clinical use of the extender in the reconstruction of significant skeletal defects. The development of new bone should couple to implant degradation in such a way that the structural integrity of the defect site is maintained throughout the recovery process Osteoinductive autograft material used in conjunction with an osteoconductive and mechanically stable resorbable scaffold would be attractive for both induction and expansion of new bone formation.

Thesaurus Terms:
biodegradable product, biomaterial development /preparation, bone prosthesis, bone regeneration, osteogenesis, polymer, tissue engineering, tissue support frame biomaterial evaluation, biomechanics, dicarboxylate histology, laboratory rat, medical implant science, sheep