Long-term BMP-2-induced bone formation in rat island and free flaps

Ectopic osteoinduction by exogenous bone morphogenetic proteins (BMPs) is rapid but heretofore characterized as transient. A rat model of carrier-free recombinant human BMP-2 intramuscular implantation was used, followed by creation of either an island flap or transplantation of a free flap. BMP-2 injection into an unaltered gastrocnemius, thigh adductor, or cutaneous trunci (thoracic wall) muscle site led to bone resorption at 4 weeks. In contrast, creation of an island or free flap of the muscle/injection site caused the newly formed ossicle to maintain its bony composition with active osteoblastic presence, from 3-8 weeks. Muscle denervation or sectioning of the Achilles tendon (for gastrocnemius injections) did not prevent bone resorption at 4 weeks. There was little osteoclastic activity within de novo bone sites of island- and free flap-injected muscles at 4 and 8 weeks. These data demonstrate that simple injection of BMP-2 into a surgically isolated flap site results in the prolonged presence of de novo bone. These findings suggest that BMP-injected island or free muscle flaps may be used to generate new bone for reconstruction of a bony defect.