The Development And Related Research Of The Injectable Osteoinductive Material With Fibrin Sealant As A Carrier

Bone defects caused by trauma, infection and tumor are always a dilemma for orthopaedic surgeons. The search for ideal bone graft substitute to repair bone defects is always an important subject in orthopaedics. Bone morphogenetic protein (BMP) has good potential in treatment for bone defects as it can induce mesenchymal cells to differentiate into cartilage cells and bone cells so to form new bone. To use BMP in practice, we must combine the protein with a proper carrier as supporting medium and to release BMP slowly. Nowadays, most studies on carrier systems of BMP focus on solid carrier systems instead of injectable delivering systems . Solid carrier systems can be used just in operation and are not suitable to the fractures and bone defects that can be treated nonoperatively. Fibrin sealant (FS)is a kind of degradable composite composed of plasma proteins, which can accelerate tissue regeneration , shape quickly in the body , has very good biocompatibility and injectable capability ,and has been widely used as hemostatic agent and adhesive material in surgery. In this study, we used it as BMP and bFGF carrier to make a new type of injectable bone graft substitute with highly effectiveosteoinductive activities. We carried out a series of studies on this composite involving its biocompatibility and osteogenic activity, and made experiments of bone defects repair on animals to study its possible clinical application. l.The effect of the injectable FS/bFGF/BMP composite on the proliferation and differentiation towards osteoblasts of marrow stromal cells of rabbitObjective: To investigate the effect of the injectable FS/bFGF/BMP composite on the proliferation and differentiation of Marrow stromal cells (MSCs)of rabbit towards osteoblasts and provide an experimental foundation for its possible clinical application in the future .Method: We investigated the influence of the material in experimental group(FS+bFGF+rhBMP-2), control group 1(FS), control group 2(FS + bFGF), control group 3 (FS + rhBMP-2) and blank control group on the proliferation, the adhesive rate, the expression of the type I collagen and Alkaline phosphatase, cells growth condition in the material and the ultrastructure of rabbit MSCs by electron microscopy, histochemical and cells culture tschniques. Results: 1. The proliferation rate and the adhesive rate of rabbit MSCs in experimental group(FS +bFGF+rhBMP-2) was significantly higher than those in control group 1(FS), control group 3 (FS+rhBMP-2) and blank control group , but significantly lower than those control group 2(FS+bFGF) (P<0.05) 2. The expression level of the type I collagen and Alkaline phosphatase in experimental group(FS+bFGF+rhBMP-2) was significantly higher than that in all control groups (P<0.05) .3. Scanning electron microscope showed that the surface of the material was rough and porous ,and that cells mixed with and grew into the material. Transmission electron microscope showed that MSCs of experimental group were mostly of the phenotype of osteoblast with high proliferation activity and high differentiation degree toward osteoblast and with plenty of extracellular matrix and collagen fibers, and that MSCs of control groups had either low differentiation degree toward osteoblast with few extracellular matrix and collagen fibers or low proliferative activity. Conclusion: The injectableosteoinductive material with fibrin sealant as a carrier compounded with BMP and bFGF could significantly accelerate the proliferation and differentiation of marrow stromal cells of rabbit towards osteoblasts.2. Experimental investigations of the effect of the injectable FS/bFGF/BMP composite on inducing ectopic bone formation of miceObjective: To investigate the effect of the injectable FS/bFGF/BMP composite on inducing ectopic bone formation of mice and provide experimental foundation for the clinical application in the future . Method: The composites of experimental group b(FS + bFGF + bBMP), control group bl(FS+bBMP), control group b2(bBMP), experimental group r(FS+bFGF+rhBM...