Enhanced Healing of Segmental Bone Defects by Modulation of the Mechanical Environment.

摘要

Large, osseous segmental defects do not heal well and are a major clinical problem. Our research is based upon the hypothesis that healing of such defects is sensitive to the mechanical environment, particularly the axial stiffness; in particular, we postulate that healing will be accelerated by first fixing the defect under conditions of low axial stiffness and then increasing the stiffness once bone begins to form. We call this reverse dynamization . A rat model was developed in which a critical size, femoral, diaphyseal defect was surgically created, treated with BMP-2 and stabilized with a custom-designed external fixator whose stiffness could be altered while still attached to a living animal. Three different axial stiffnesses were tested: low (114 N/mm), medium (185 N/mm) and high (254 N/mm). Pilot studies showed that, under non-dynamized conditions, low stiffness fixation provided the best outcome. Reverse dynamization was explored with low stiffness fixation for the first 14 days, during which time bone began to form in the defect, followed by high stiffness fixation for the remaining 6 weeks of the experiment. Reverse dynamization had a dramatic effect on healing, leading to accelerated bridging and advanced remodeling of the newly formed bone. After 8 weeks the strength of the healed bone under reverse dynamization was considerably enhanced, suggesting an early return to normal mechanical properties. Experiments to test this empirically are underway, but could not be completed in time for this report. Another possibility, that reverse dynamization could reduce the need for BMP-2, was tested empirically but this did not appear to be the case. Reverse dynamization accelerated and improved the healing of a defect treated with an effective dose of BMP-2 but was unable to initiate healing in a defect treated with an inactive dose of BMP-2.