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

Abstract

Background 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 b-tricalcium phosphate (b-TCP) and collagen in repairing segmental bone defects. Methods 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 b-TCP granules and collagen, with or without 100 lg recombinant human HGF. Biweekly, bone regeneration and b-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. Results Compared with the bone tissue treated with b-TCP and collagen, mineralization, angiogenesis, new bone formation, and absorption of b-TCP were promoted 4 weeks postoperatively by treatment with HGF in the b-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 b-TCP granules were completed in a shorter period by combining HGF with b-TCP and collagen, compared with tissues without HGF. Conclusions The combined application of HGF in a b-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 b-TCP for treatment of bone defects made a substantial difference.

Combined Administration of BMP-2 and HGF Facilitate Bone Regeneration through Angiogenic Mechanisms

“…In the defects treated with BMP-2+HGF, most of the gelatin sponge was absorbed and replaced by newly formed bone with bone marrow four weeks after surgery. Since HGF is a potent antifibrotic agent 53) and facilitates the resorption of the biological scaffold 54) comprising extracellular matrix, HGF may help to promote the absorption of the gelatin sponge, which could improve the environment for bone regeneration in the defect area. However, the impact of HGF on the degradation of extracellular matrix is still under investigation.…”

Repair of segmental long-bone defects by stem cell concentrate augmented scaffolds: a clinical and positron emission tomography - computed tomography analysis

“…Plain scaffolds and scaffolds loaded with MSC provided less bone formation than the autograft and rhBMP-7 group [19]. Goshima et al [20] performed a study on segmental bone defect repair in tibial shafts of rabbits using β-tricalcium phosphate (β-TCP) scaffolds loaded with hepatocyte growth factor (HGF). They found that HGF-loaded scaffolds promoted mineralisation, angiogenesis, new bone formation and β-TCP absorption [20].…”

“…Goshima et al [20] performed a study on segmental bone defect repair in tibial shafts of rabbits using β-tricalcium phosphate (β-TCP) scaffolds loaded with hepatocyte growth factor (HGF). They found that HGF-loaded scaffolds promoted mineralisation, angiogenesis, new bone formation and β-TCP absorption [20]. Sauerbier et al [21] and Rickert et al [22] performed randomised controlled clinical trials to investigate formation of new bone in patients with severe atrophy of the maxillary sinus.…”

Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair

“…Increased β-TCP resorption indicates greater repair of the bone defect. After eight weeks a slight amount of bone formation was visible in the untreated controls, while both treatment groups showed a substantial increase in bone density and volume 60 . Additionally, the group treated with the combination of β-TCP, collagen, and HGF had a larger area of new bone formation at weeks 2, 4, and 6 and smaller area of β-TCP, suggesting more β-TCP was resorbed and replaced by newly formed bone 60 .…”

“…The local expression of HGF in the microenvironment of a bone fracture showed enhanced healing of the bone fracture in rabbits 59 . Furthermore, a rabbit model of a bone defect showed that HGF in combination with β-tricalcium phosphate (β-TCP) and collagen was more effective than the β-TCP and collagen treatments alone or the untreated control 60 . β-TCP is used as a bone substitute when repairing bone defects due to its resorbability and biocompatibility, allowing it to enable surface bone growth.…”