Heparin increases the osteogenic effect of recombinant human bone morphogenetic protein-2 in the rabbit bone defect model

Abstract

In order to perform successful dental implantations and solve other problems such as bone deficiencies, it is important to find suitable biomaterials to enhance osteoinduction. Heparin has been known to enhance bone morphogenetic protein 2 (BMP-2) induced-bone formation. We histomorphometrically investigated the enhancing effects and roles of heparin to recombinant human bone morphogenetic proteins-2 (rhBMP-2). For morphologic study, stem cells obtained from rabbit adipose tissue were divided into four groups based on heparin concentrations, with a constant rhBMP-2 concentration. They were cultured for 2, 4, and 8 days. Alkaline phosphatase and calcium content were measured as time schedules. In addition, a mixture of rhBMP-2 and heparin was blotted into multiporous anorganic bovine bone and was inserted into calvarial defects in rabbits. The harvested tissues were stained using the Hematoxylin & Eosin (H&E) and Masson's trichrome (MT) stain. And the areas of newly formed bone in the grafted material were analyzed. In morphologic results, the degree of osteoblastic differentiation was significantly increased with increasing heparin concentrations, but the cellular degeneration was accelerated at a higher concentration of heparin as time passed. In histological results, the more higher the concentration of heparin, larger newly formed bone in grafted materials was also observed in the initial period. However, the increased amount of the newly formed bone in grafted materials was progressively decreased at higher concentrations of heparin as time passed. In conclusion, heparin might have an influence on the osteoinductive effects of rhBMP-2 during the initial stage of bone formation.