Bioactive Peptide Coatings for Synthetic Bone Grafts in Dental Applications

DESCRIPTION (provided by applicant): According to the National Institute of Dental and Craniofacial Research, 86% of adults over 70 years have at least moderate periodontitis and over a quarter have lost their teeth, which has serious repercussion on health and quality of life. Because of bone loss caused by this disease, bone grafting is routinely necessary prior to the placement of dental implants. Autograft bone is considered the gold standard because of its osteogenic cells, osteoinductive factors, and osteoconductive properties. However, because of procurement morbidity and constraints on the quantity of autograft, surgeons also use allografts, xenografts, and synthetic materials. Allograft and xenograft are favored because they possess some osteoinductive elements especially in demineralized forms. However, these natural materials also have limitations including immunogenicity, risk of disease transmission, limited availability, and high procurement costs. Many synthetic alternatives have been developed, but they are generally not as effective as the natural materials due to the absence of osteoinductive and osteogenic properties. In this project, we are attempting to improve synthetic bone substitutes with Affinergy's linker peptides. If synthetics were made more osteoinductive, they could provide an unlimited source of graft material that would eliminate many of the drawbacks of autograft, allograft, and xenograft. Affinergy's peptide linkers provide two improvements on existing bone grafts that could significantly improve clinical outcomes by stimulating bone healing. First, we expect that coating bone graft materials with binding peptides will significantly improve their ability to retain exogenously delivered osteogenic factors such as recombinant proteins and progenitor cells. Secondly, we believe these peptide coatings have the potential to promote the attachment of endogenous growth factors and cells onto the surface of bone grafts. The goal of this proposal is to demonstrate that bi-functional peptide coatings can improve the ability of a synthetic bone graft to promote bone healing by increasing the attachment and retention of osteogenic growth factors and cells. First, using phage display techniques, we will identify tricalcium phosphate (TCP) binding peptides. Next, we will synthesize combinations of Affinergy's existing BMP-2 and osteoblast binding sequences and the newly identified TCP binding peptides. These candidate bi-functional linker peptides will be tested for their ability to bind BMP-2 and osteoblasts on TCP matix, while retaining BMP-2's activity and the osteolbasts' phenotype. Finally, a rat mandible defect model will be used to investigate the ability of peptide coatings to increase bone formation at lower doses of recombinant BMP-2. Growth factor and osteoblast binding peptides will also be tested alone and in combination to assess their ability to increase bone formation compared to untreated TCP by promoting the attachment of endogenous growth factors and osteoprogenitor cells. Bone grafting is routinely necessary prior to the placement of dental implants. Natural materials like autograft, bone harvest from the patient, and allograft, cadaveric bone, have traditionally been used in these grafting procedures. They have many limitations including complications associated with autograft harvest; and immunogenicity, risk of disease transmission, limited availability, and high procurement costs associated with allograft. Many synthetic alternatives have been developed, but they are generally not as effective as the natural materials. In this project, we are attempting to improve synthetic bone substitutes with Affinergy's linker peptides. We expect that peptide coatings will improve the ability of synthetic materials to stimulate bone healing by promoting the attachment of bone promoting growth factors and cells on the surface of these synthetic alternatives.