Bone Morphogenetic Protein-2 Incorporated Beta-Tricalcium Phosphate Enhanced Bone Regeneration of Critical-Sized Bone Defects in Rats

Abstract

Although preclinical and clinical studies have shown the benefits of bone morphogenetic protein-2 (BMP2) in bone regeneration, there are increasing concerns about its side effects. These are mainly due to the high dosage of BMP2 which is necessary to obtain the desired clinical results. Previously our group has developed a novel controlled-release delivery system; the biomimetic calcium phosphate coating incorporated with BMP2. It can be used at much lower concentrations of BMP2 than those used in the commercially available product and still produce similar biological effects. In this study, we made a primarily biological evaluation of BMP2 incorporated beta-tricalcium phosphate (β-TCP) for bone regeneration in critical-sized bone defects. Critical-sized calvarial defects were created in rats. They were divided into four groups as follows: (1) empty defects (control), (2) defects filled with β-TCP, (3) defects filled with BMP2 incorporated β-TCP, (4) defects filled with autologous bone. Eight weeks after the operation, the efficiency of the materials was evaluated using histology and histomorphometry. Moreover, the safety of the materials was evaluated using routine blood examination, blood biochemistry examination and histopathological examination of viscera. BMP2 incorporated β-TCP demonstrated an efficiency of bone regeneration that was comparable with autologous bone, with the highest levels of new bone formation (38.3±8.4 mm3 versus 30.1±9.9 mm3, p < 0.05). All clinical lab index of blood in these four groups were within the normal range. Moreover, no change related to the treatment was noted in the histopathological examination of viscera. The results from the present study demonstrated that BMP2 incorporated β-TCP could be a promising substitute for autologous bone used for bone regeneration. Future clinical trials and preclinical trials with large animal models are necessary to investigate the safety and efficacy of BMP2 incorporated β-TCP.