Local administration of low-dose simvastatin-conjugated gelatin hydrogel for tendon-bone healing in anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) reconstruction with the hamstring tendon graft takes a long time, as the tendon graft needs to heal at the site of the bone-tendon integration in the created bone tunnels. Several reports have shown the therapeutic effects of simvastatin on bone formation with neovascularization. The aim of this study was to test the hypothesis that enhanced angiogenesis and osteogenesis by locally applied simvastatin promotes tendon-bone healing after ACL reconstruction. Rabbits received ACL reconstruction with hamstring tendon graft and were implanted with either simvastatin-conjugated gelatin hydrogel or gelatin hydrogel alone in their bone tunnels, and then bone regeneration and neovascularization at tendon-bone interface and biomechanical properties were assessed. Histological analysis at week 2 demonstrated that tendon-bone healing was significantly greater with angiogenesis and osteogenesis in the simvastatin-treated group than in the control group. Computed tomography at weeks 2 and 4 showed a significantly smaller tibial bone tunnel in the simvastatin-treated group. Biomechanical testing at week 2 demonstrated a significant increase in ultimate failure load in the simvastatin-treated group. This study suggested that local administration of low-dose simvastatin-conjugated gelatin hydrogel promotes the tendon-bone healing via its effect on both angiogenesis and osteogenesis at an early phase in a rabbit model, but does not affect biomechanical property in long-term after ACL reconstruction.