Modification of an osteoconductive anorganic bovine bone mineral matrix with growth factors

Background: Osteoconductive anorganic bovine bone mineral matrix material h as been used clinically in bone regeneration procedures. Platelet-derived g rowth factor-BE (PDGF-BB) and insulin-like growth factor (IGF-I) are import ant anabolic growth factors for bone. It was the aim of these studies to 1) examine the interaction of this bone graft material with PDGF-BB and IGF-I and 2) determine if the combination of growth factors with the matrix coul d stimulate osteoblastic cell proliferation. Methods: Adsorption of PDGF-BB and IGF-I was done using I-125 radiolabeled growth factors. The PDGF-BB or IGF-I was incubated with the anorganic bovin e bone matrix, and the amount of adsorbed growth factor was measured. In th e desorption studies, radiolabeled growth factors were adsorbed to the matr ix material. The samples were incubated in buffer for various time periods, and the amount remaining on the matrix was measured to calculate the perce ntage of released growth factor. The biological activity was tested in an i n vitro assay with primary culture neonatal rat osteoblastic cells. Porous bone matrix with known amounts of adsorbed PDGF-BB or IGF-I was produced. T he osteoblastic cells were cultured on the bone mineral matrix, with and wi thout adsorbed growth factor, and proliferation was assessed by H-3-thymidi ne incorporation. Results: Both PDGF-BB and IGF-I adsorbed to bone mineral matrix in a concen tration-dependent fashion. The affinity of IGF-I for the material was 10-fo ld greater than PDGF-BB. In the experiments that measured the release of th e initially adsorbed growth factors, approximately 50% of the PDGF-BB and 1 0% of the IGF-I were released after 10 days. PDGF-BB adsorbed to the matrix material significantly (P <0.05, ANOVA) enhanced the proliferation of cult ured osteoblastic cells compared to the mineralized matrix alone. However, IGF-I adsorbed to the matrix material did not significantly enhance cell pr oliferation. Conclusions: These results suggest that PDGF-BB can be adsorbed to the anor ganic bovine bone mineral matrix and that this growth factor subsequently e nhances the osteogenic properties of this bone graft material. IGF-I also a dsorbed to the graft material; however, it was not readily released and it did not produce significant effects in the biologic assay. It appears that it may be clinically feasible to adsorb PDGF to anorganic bovine bone and t hat this combination of bone growth factor and mineral matrix has the poten tial for clinical applications.