[Heterotopic and orthotopic bone formation with a vascularized periosteal flap, a matrix and rh-BMP-2 (bone...

The purpose of this study was to construct a vascularized bone graft using the osteoinductive bone morphogenetic protein (rh-BMP-2), a polylactic acid matrix (OPLA/HY), and a vascularized periosteal flap containing osteoprogenitor cells ectopically in the groin or orthotopically in a femoral defect. In the Lewis rat, periosteal flaps were harvested from the medial surface of the tibia vascularized by the saphenous artery and vein and were transferred to the groin on its vascularized pedicle. Alternatively, the periosteal flap along its pedicle was transferred between the thigh muscles to be wrapped around a femoral defect of 1 cm. The animals were divided into 10 groups (82 animals). In group 1, the periosteal flap was left empty in the groin. Groups 2 and 3 consisted of the periosteal flap and 20 micrograms rh-BMP-2, but in group 3 the vascular pedicle was ligated proximally. In group 4 the flap was harvested without the periosteal layer and turned "inside out". Groups 5 and 6 consisted of the periosteal flap and the matrix OPLA/HY +/- 20 micrograms rh-BMP-2. In the femoral defect model, bone formation was studied using the matrix OPLA/HY alone (group 7) or combined with the vascularized periosteal flap (group 8), or in combination with OPLA/HY + BMP (group 9) or OPLA/HY + BMP + the periosteal flap (group 10). The presence and density of new bone formation in the groin and femoral defect were evaluated radiologically and histologically at 4 and 8 weeks. Good bone formation in the groin chamber (ectopic) was demonstrated in the periosteal flap + OPLA/HY + BMP group. In the femoral defects, good bone formation (orthotopic) was seen in the OPLA/HY + BMP + the periosteal flap groups. However, with the presence of a vascularized periosteal flap, more bone formation along the rim of the defect was observed. This study of ectopic bone formation in the groin and orthotopic bone formation in the femoral defect demonstrates that optimal bone formation requires four factors: BMP, a biodegradable matrix, osteoprogenitor cells, and blood supply. Potentially in the future, this technique could be used to reconstruct a bony defect or a nonunion by covering the involved area with a vascularized periosteal flap and a suitable matrix combined with BMP. Alternatively, a vascularized bone graft could be prefabricated at a distant site and then transferred microsurgically into a defect.