Local delivery of rhVEGF165 through biocoated nHA/coral block grafts in critical-sized dog mandible defects: a histological study at the early stages of bone healing

摘要

Alveolar defects of a critical size cannot heal completely without grafting. Thus, they represent a major clinical challenge to reconstructive surgery. Numerous types of grafts have been used to improve bone regeneration. In the case of particle grafts, the capacity for volume rebuilding and space maintaining is still not ideal, particularly for critical-sized bone defects. Although porous block grafts can overcome the above problems of particle grafts, they are still not widely used for critical-sized alveolar defects, because of their reduced efficacy in blood vessel and bone formation. Thus, in the present study, nano-hydroxyapatite/coralline (nHA/coral) blocks were pre-vascularized by coating them with vascular endothelial growth factor (VEGF), and then implanted in dogs with critical-sized mandibular defects. This model has possible applications in orthopedic and implant surgery. In vivo results indicate that the nHA/coral blocks allow cell and collagen ingrowth because of their suitable pore size and interconnectivity of pores. In addition, pre-vascularization properties were obtained by coating the scaffolds with VEGF. Histological and immunohistochemical examinations, as well as fluorescence analysis, revealed that the local delivery of VEGF can significantly improve neovascularization and mineralization of newly formed bone at the early stages of bone healing in this dog implantation model. Our data collectively show that nHA/coral blocks have possible applications in bone tissue engineering, and excellent results can be achieved by pre-vascularization with VEGF.