Promotion of rabbit ligament healing by local delivery of hepatocyte growth factor

Extracapsular ligament injuries of the knee and ankle are common injuries. Ligaments heal slowly, usually over months or longer by scar formation rather than by tissue regeneration. This study was performed to evaluate the therapeutic effect of locally delivered recombinant hepatocyte growth factor (HGF) on the early healing of ligaments in a rabbit model.

Japanese white rabbits were subjected to a standardized gap injury in the medial collateral ligaments (MCLs) of both knees. Each rabbit underwent bilateral transection of the midsubstance of the MCL, which was not repaired. During postoperative days 0-6, the rabbits were injected with 10 μg human recombinant HGF into the right MCL, while the left MCL was injected with saline alone. One, 3, 6, and 12 weeks after surgery, experimental rabbits were sacrificed. The structural properties of the femur-MCL-tibia complex were then assessed and the tissue was subjected to histological evaluation. To see the distribution of cells that express c-Met receptor, the tissue was subjected to immunohistochemistry.

Immunohistochemical evaluation revealed that c-Met expression was observed particularly at opposing ligament ends in the HGF-treated limbs 1 week after surgery. Histological evaluation revealed earlier neovascularization and more aligned collagen fibers in the MCLs of the HGF-treated group than the control group. In mechanical evaluations, similar ligament failure modes were noted in the two groups. After 3 weeks, HGF-treated limbs had significantly improved structural properties than the paired control limbs.

Our findings indicate local administration of recombinant HGF promotes early steps in ligament healing and the repair of structural properties in a rabbit model. Local administration of HGF may represent a new therapeutic approach to accelerating healing and rehabilitation after ligament injury.