The biological basis of the bone-muscle inter-relationship in the algorithm of fracture healing.

The biological cascade of fracture healing is intimately linked to the muscle envelope. It further depends on the preservation of stable, perpetual axial micromovements. The current study was designed to demonstrate that high molecular weight bioactive substances diffuse from the muscle envelope to initiate osteoinductive activity at experimental fracture sites. Forty-eight rats underwent an experimental fracture of the left tibia and stabilization with an intramedullary 20-gauge needle. The animals were divided into 4 groups (A-D) of 12 rats each according to the post-fracture treatment. In group A (control) no additional treatment was applied following fracture and intramedullary fixation. In groups B, C, and D, a nitrocellulose membrane of various sizes was wrapped around the fracture, separating the periosteum from the muscle envelope. The groups differed by the membrane pore size, allowing passage of the following molecular sizes: 50 kilodaltons (kDa), 12 to 14 kDa, and 3.5 kDa in groups B, C, and D, respectively. Four animals in each group were sacrificed 2, 5, and 10 weeks after the procedure for radiographic and histological evaluation of fracture healing. Radiographic evaluation revealed a decreased rate of bone synthesis that correlated with the nitrocellulose pore size. Morphological and functional analysis of the bone explants indicated poorly healed fractures in groups B, C, and D. Direct contact between fractured bone and its muscle envelope is essential for the biological sequence of new bone formation. The extent of obstruction between the fracture and its muscle envelope correlates with the delay in fracture healing.