Bone inductive potential and dose-dependent response of bovine bone morphogenetic protein combined with type IV...

Using type IV collagen as carrier, the expression of bovine bone morphogenetic protein (bBMP) activity and the relation of ectopic bone formation to BMP dosage in the reconstitution were investigated in BALB mice. Visible heterotopic bone was induced by GuHCl-extracted bovine BMP at a minimal dose of 0.5 mg within 21 days after the BMP was covalently bound to type IV collagen of weight 5.6 mg. The dose-dependent osteogenetic response of BMP was retained in the BMP/type IV collagen composite. As the BMP dose increased in the reconstitution, the integrated intensity and area of bone and cartilage formation, as quantified by a computerized scanner, were enhanced. Degradation of the collagenous carrier was improved by BMP, and neovascularization of the implant site initiated by type IV collagen was also observed. The covalent binding of BMP to type IV collagen postponed the time-sequence of ectopic bone development induced by BMP alone. The conclusion was that the exaggerated and extended effects of type IV collagen on BMP are mainly due to chemotaxis to progenitor cells, immunogenetically inert, vascular initiation and biodegradability in type IV collagen.