Effect of Recombinant Human Bone Morphogenetic Protein‐2, ‐4, and ‐7 on Bone Formation in Rat Calvarial Defects

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Abstract
Currently, more than 20 bone morphogenetic proteins (BMPs) have been identified, and many trials have been carried out using recombinant human BMPs (rhBMPs) for bone tissue engineering. However, comparative analyses on bone formative activities of rhBMP using a preclinical model have been limited. Therefore, the aim of this study was to evaluate and compare the osteogenic potential of rhBMP-2, -4, and -7 delivered with absorbable collagen sponge (ACS) upon early (2 weeks) and complete (8 weeks) wound healing phases in a critical sized rat calvarial defect model. Eight-millimeter critical sized calvarial defects were created in 30 male Sprague-Dawley rats. The animals were divided into three groups of 10 animals each. The defects were treated with 0.025 mg/ml rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS. The rats were sacrificed at either 2 (five rats) or 8 (five rats) weeks after surgery, and the results were evaluated histologically, histomorphometrically, and immunohistometrically. The surgical implantation of rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS resulted in enhanced local bone formation in the rat calvarial defect model at both 2 and 8 weeks. The amount of defect closure, new bone area, and bone density were similar in the three groups at each time point (P > 0.05). In terms of bone density and new bone area, there were statistically significant differences between results obtained at 2 weeks and those obtained at 8 weeks in all groups (P < 0.05). Two-way analysis of variance (ANOVA) revealed that there was no correlation between the time and conditions (P > 0.05), but time was found to have a strong influence on defect closure, new bone area, and bone density (P < 0.05). Irrespective of rhBMP type, positive immunoreactions of osteopontin (OPN) and osteocalcin (OCN) were evident at 2 and 8 weeks. Intense OPN and OCN staining was observed near the newly formed bone as well as in some cells within the new bone. Within the rhBMP types used, rhBMP concentration, and the observation interval, there appears to be no specific differences in bone regenerative potential. All rhBMPs used in this study may be considered effective factors for inducing bone formation.