BMP-9-transduced prefabricated muscular flaps for the treatment of bony defects

Autologous bone grafting techniques involve the use of tissues that need to be extracted from healthy sites. This can lead to significant donor site morbidity that causes a one-site defect to become a two-site defect. Bone grafts can be especially difficult to manipulate, because bone is a relatively nonmoldable tissue. Furthermore, the inability of a bone graft to contain a transplantable vascular supply also limits the possible size that such a bone graft can be. Because of these limitations, a graft that was moldable with a vascular supply would possess significant advantages in reconstructive applications. In this research, gene therapy techniques were used to create such a graft. An adenovirus expressing BMP-9 was injected into the latissimus dorsi of a nude animal to cause bony differentiation of that muscle. Differentiation of the muscle to cartilage in bone was measured by reverse transcription polymerase chain reaction and immunohistochemistry to determine the optimal time of flap elevation. After injection of the BMP-9 virus, the animals were biopsied weekly over a 3-week period. Both bone and cartilage markers were discovered in these tissues over the study period. Optimal flap elevation time was established to be 2 weeks after injection of the virus.