Ultrastructural study of direct bone formation induced by BMPs-collagen complex implanted into an ectopic site.

Objective: Some authors have reported that direct bone formation is ectopically induced by bone morphogenetic proteins (BMPs) independently of cartilage formation when type I collagen is used as a carrier. This study ultrastructurally investigated the mechanism of direct bone formation by BMPs-collagen complex.

Materials And Methods: Partially purified BMPs were combined with atelopeptide type I collagen (AC) and were implanted into the calf muscles of rats (n = 20). Tissue specimens were removed on days 7, 10, 14, and 21 after implantation.

Results: Ultrastructurally, several regions near the pellet rim showed evidence of early calcification on day 10. In the uncalcified regions, mitochondrial calcification was seen in mesenchymal cells near AC fibers. The initially calcified regions contained numerous calcified granules deposited in the AC fibers. Some of these granules adhered to the cell membrane of osteogenic cells. In the highly calcified regions, some osteogenic cells secreted uncalcified matrix and deposited needle-like crystals and calcified collagen microfibrils on the AC fibers.

Conclusion: This study suggests that the mesenchymal cells invading BMPs-AC complex closely contacted the AC fibers, differentiated into osteogenic cells, and deposited calcified matrix on the AC fibers, resulting in direct osteoinduction without cartilage formation.