Carrier dependent cell differentiation of bone morphogenetic protein‐2 induced osteogenesis and chondrogenesis during the early implantation stage in rats

Abstract To evaluate the osteoinductive effects of recombinant human bone morphogenetic protein (rhBMP)‐2 during the early stages of rat ectopic bone formation, we prepared two distinct carriers. Two carriers, insoluble bone matrix (IBM) and fibrous glass membrane (FGM) were combined with rhBMP‐2 and implanted into the backs of rats to evaluate the osteoinductive effects of the two rhBMP‐2 carrier systems. Insoluble bone matrix particle size was 320 to 620 μm. Fibrous glass membrane was constructed from unwoven glass fibers 1 μm in diameter. Alkaline phosphatase (ALP) activity and type II collagen were detected in IBM/rhBMP‐2 at 5 days postimplantation. Calcium (Ca) was also detected in IBM/rhBMP‐2 at 7 and 9 days postimplantation. In contrast, ALP and type II collagen were detected in FGM/rhBMP‐2 at 7 days. Calcium was undetected, indicating that the bone formation in IBM/rhBMP‐2 proceeded faster than in FGM/rhBMP‐2 during the early stage of BMP‐induced osteogenesis. In addition, mRNA expression level of KDR, a receptor for vascular endothelial growth factor, was also increased in IBM/rhBMP‐2. To investigate the in vivo release profile of rhBMP‐2, iodine 125 (¹²⁵I)‐labeled BMP‐2–incorporating IBM and FGM implants were inserted into the back subcutis of mice. More than 60% of the rhBMP‐2 was released from the IBM/rhBMP‐2 carrier within 1 day after implantation, whereas 50% of the rhBMP‐2 was released from the FGM/rhBMP‐2 10 days postimplantation. These results indicated that osteo‐ and chondrogenesis depends highly upon the geometry of the carrier and the in situ retention of rhBMP‐2 during the early stage of rhBMP‐2 induced bone formation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 181–189, 2004