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.