Primary Study On The Effect Of Thiolated N-alkylated Chitosan Mediated PIRES-hVEGF₁₂₁cDNA/hBMP-4 In Repairing Radial Bone Defects Of Rabbits

Causes such as trauma or tumor of bone defects, bone regeneration and repair of non-union fractures has been plagued reconstruction surgery critical challenges, it has wide variety of treatment methods and their advantages and disadvantages. Currently in the field of basic research and clinical treatment, gene therapy is its research focus. Local gene therapy of bone defects with osteogenic effect of gene with viral or non-viral gene expression vector or plasmid transfer in vivo or in vitro expansion of channels into the target cells, transcribed into mRNA by the target cells and translated into proteins. Depend on the role of proteins, target cells were stimulated differentiation by an autocrine or paracrine manner to promote osteogenesis. With the development of recombinant technology, an increasing number of growth factors involved in bone repair genes have been successfully cloned, making gene therapy for bone defects as a possibility. The advantages of this method are: the local and targeted gene product can be released; to maximize the local therapeutic effect and reduce systemic side-effects; multiple genes respectively transduction, regulation and control, respectively, than endogenous synthesis of exogenous proteins recombinant protein has a greater biological activity and so on. Gene therapy is considered to maintain bone defect an effective therapeutic concentrations of local growth factor in the most promising methods. Since Urist (1965 years) first discovered and prepared out of cow bone morphogenetic protein (Bone Morphogenetic Protein, BMP) since the crude extract, BMP has been widely used in bone defects, and ectopic bone research. BMP is the start of bone growth factor, can induce bone marrow stromal cells differentiate into bone cells and bone cells, to promote calcification, resulting in calcification of bone matrix. But the repair of bone defects is a complex subject to a variety of cytokines in the process of regulation, each molecule has a specific role of time and specific functional areas.Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Study more at home and abroad is used BMP and vascular endothelial growth factor (VEGF) synergy to repair bone defects. VEGF is a platelet-derived growth factor belongs to a family member of the body to promote blood vessel growth is the most important growth factor, could be specifically acts on endothelial cells, promoting their proliferation and angiogenesis, involved in bone regeneration and repair process, at different stages of fracture healing in almost all expression, directly or indirectly affect bone repair and regeneration of blood vessels in all aspects. Number of studies have shown that VEGF can be combined with the BMP to promote bone tissue regeneration and repair, but the synergy between the mechanism is not yet clear, due to selection caused by differences in gene vector transfection efficiency is not the same. Thus, a variety of bone regeneration is how the interaction between growth factors to promote bone regeneration; choice of side-effects of a small carrier with high transfection efficiency, and transformation of gene vector to improve gene transfer efficiency, to achieve targeted gene transfer and can be regulation is required to in-depth study .The research group constructed pIRES-hVEGF_l2lcDNA/hBMP-4 eukaryotic expression plasmid pairs into the bone to the direction of research early has a clear .The purpose of this study will be prepared by Thiolated N-alkylated chitosan (TACS) mediated pIRES-hVEGF_l2lcDNA/hBMP-4 dual-core co-expression plasmid used in animal experiments, observations of its role in repair of bone defects.