Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor.

Abstract

Segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on bone tissue engineering. Clinical studies are ongoing to address application of hepatocyte growth factor (HGF) for treatment of some diseases; however, the use of HGF in bone tissue engineering has not been addressed. This study was performed to evaluate the effect of HGF in a complex of β-tricalcium phosphate (β-TCP) and collagen in repairing segmental bone defects. Segmental bone defects 5 mm long were created in the middle of the tibial shafts of rabbits. The defect was stabilized with external fixators and implanted with a complex of β-TCP granules and collagen, with or without 100 μg recombinant human HGF. Biweekly, bone regeneration and β-TCP resorption were assessed radiographically and histologically. At 4 and 8 weeks, bone regeneration was evaluated by use of micro-computed tomography and mechanical tests. Compared with the bone tissue treated with β-TCP and collagen, mineralization, angiogenesis, new bone formation, and absorption of β-TCP were promoted 4 weeks postoperatively by treatment with HGF in the β-TCP and collagen group. These changes were associated with promoting biomechanical regeneration. By 8 weeks, the formation of bone marrow in newly generated bone and absorption of the β-TCP granules were completed in a shorter period by combining HGF with β-TCP and collagen, compared with tissues without HGF. The combined application of HGF in a β-TCP and collagen matrix promoted histological bone healing and augmented mechanical strength of the healing bone, particularly in the early stages. The combined use of HGF and β-TCP for treatment of bone defects made a substantial difference.