SEM study on microvascular changes following implantation of bone morphogenetic protein combined with hydroxyapatite into experimental bone defects.

BMP-HAP complex was implanted into a bone defect in the femur of Wistar-strain rats, and animals were allowed to heal for one to 8 weeks prior to sacrifice. Similar bone defects without BMP-HAP complex served as controls. Osseous healing and microvascular changes, as revealed by plastic microcorrosion castings, were subsequently examined under a scanning electron microscope. One week after implantation, sproutings and congregate sinusoidal capillary plexuses and primary bone trabeculae (woven bone) were observed around and between the BMP-HAP complexes. Control specimens revealed a fine and immature sinusoidal capillary plexus arising from sproutings and elongations of pre-existing blood vessels, but bone formation was not observed. At two weeks, newly-formed trabeculae were observed around and on the surface of the HAPs, and a network of thick, newly-formed vessels was observed in intervening space. At three weeks, networks of newly-formed vessels were observed on the surface of the HAPs, and surrounding newly-formed trabeculae had become thickened. At four weeks, bone defects were filled, and HAP was completely embedded in new bone. At eight weeks, the HAP was fused with new bone, and the boundary between the HAP and new bone was unclear. In comparison with comparable surgically created control bone defects without implanted BMP-HAP complex, BMP apparently stimulates new vascularization. Further, implanted BMP-HAP apparently stimulates undifferentiated mesenchymal cells to differentiate into angioblasts and osteoblasts, or vice versa (dedifferentiation).