Enhancement of tendon-bone osteointegration of anterior cruciate ligament graft using granulocyte colony-stimulating factor.

BACKGROUND: Whereas anterior cruciate ligament rupture usually requires reconstruction, the attachment between the tendon and the bone is the weakest region in the early posttransplantation period. In this process, the acquisition of appropriate vascularity is a key for early bone-tendon healing.

HYPOTHESIS: Granulocyte colony-stimulating factor has an effect on the maturation of bone-tendon integration of anterior cruciate ligament reconstruction.

STUDY DESIGN: Controlled laboratory study.

METHODS: Twenty-eight healthy adult beagle dogs underwent bilateral anterior cruciate ligament reconstruction using the ipsilateral flexor digitorum superficialis tendon and were divided into 2 groups. A granulocyte colony-stimulating factor-incorporated gelatin surrounded the graft in the granulocyte colony-stimulating factor group, and the same gelatin without granulocyte colony-stimulating factor was used as the control group. Assessment was done at 2 and 4 weeks.

RESULTS: Histological analysis at week 2 demonstrated that, in addition to more Sharpey fibers, microvessels were significantly enhanced in the granulocyte colony-stimulating factor group's grafts. Computed tomography at week 4 showed a significantly smaller tibial bone tunnel in the granulocyte colony-stimulating factor group. Real-time polymerase chain reaction revealed significantly elevated messenger ribonucleic acid expression levels of vascular endothelial growth factor and osteocalcin in the tibial bone tunnel and graft compared with controls. Furthermore, biomechanical testing of force during loading to ultimate failure at week 4 demonstrated a significant increase in strength in the granulocyte colony-stimulating factor group.

CONCLUSION: This study demonstrated that a local application of granulocyte colony-stimulating factor-incorporated gelatin significantly accelerates bone-tendon interface strength via enhanced angiogenesis and osteogenesis.

CLINICAL RELEVANCE: Granulocyte colony-stimulating factor has therapeutic potential in promoting an environment conductive to angiogenesis and osteogenesis in bone tunnels.