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

Abstract

Osteoconductive anorganic bovine bone mineral matrix material has been used clinically in bone regeneration procedures. Platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor (IGF-I) are important 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 could stimulate osteoblastic cell proliferation. Adsorption of PDGF-BB and IGF-I was done using 125I radio-labeled growth factors. The PDGF-BB or IGF-I was incubated with the anorganic bovine bone matrix, and the amount of adsorbed growth factor was measured. In the desorption studies, radiolabeled growth factors were adsorbed to the matrix material. The samples were incubated in buffer for various time periods, and the amount remaining on the matrix was measured to calculate the percentage of released growth factor. The biological activity was tested in an in vitro assay with primary culture neonatal rat osteoblastic cells. Porous bone matrix with known amounts of adsorbed PDGF-BB or IGF-I was produced. The osteoblastic cells were cultured on the bone mineral matrix, with and without adsorbed growth factor, and proliferation was assessed by 3H-thymidine incorporation. Both PDGF-BB and IGF-I adsorbed to bone mineral matrix in a concentration-dependent fashion. The affinity of IGF-I for the material was 10-fold greater than PDGF-BB. In the experiments that measured the release of the initially adsorbed growth factors, approximately 50% of the PDGF-BB and 10% 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 cultured osteoblastic cells compared to the mineralized matrix alone. However, IGF-I adsorbed to the matrix material did not significantly enhance cell proliferation. These results suggest that PDGF-BB can be adsorbed to the anorganic bovine bone mineral matrix and that this growth factor subsequently enhances the osteogenic properties of this bone graft material. IGF-I also adsorbed 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 that this combination of bone growth factor and mineral matrix has the potential for clinical applications.