Improved Bone Morphogenetic Protein-2 Retention in an Injectable Collagen Matrix Using Bifunctional Peptides

To promote healing of many orthopedic injuries, tissue engineering approaches are being developed that combine growth factors such as Bone Morphogenetic Proteins (BMP) with biomaterial carriers. Although these technologies have shown great promise, they still face limitations. We describe a generalized approach to create target-specific modular peptides that bind growth factors to implantable biomaterials. These bifunctional peptide coatings provide a novel way to modulate biology on the surface of an implant. Using phage display techniques, we have identified peptides that bind with high affinity to BMP-2. The peptides that bind to BMP-2 fall into two different sequence clusters. The first cluster of peptide sequences contains the motif W-X-X-F-X-X-L (where X can be any amino acid) and the second cluster contains the motif F-P-L-K-G. We have synthesized bifunctional peptide linkers that contain BMP-2 and collagen-binding domains. Using a rat ectopic bone formation model, we have injected rhBMP-2 into a collagen matrix with or without a bifunctional BMP-2: collagen peptide (BC-1). The presence of BC-1 significantly increased osteogenic cellular activity, the area of bone formed, and bone maturity at the site of injection. Our results suggest that bifunctional peptides that can simultaneously bind to a growth factor and an implantable biomaterial can be used to control the delivery and release of growth factors at the site of implantation.