载VEGF和BMP-2的PDLLA涂层螺钉治疗股骨颈骨折的实验研究

Effect of PDLLA Coating Screw Carrying VEGF and BMP-2 on Femoral Neck Fracture

目的探讨载血管内皮生长因子(VEGF)和骨形成蛋白2(BMP-2)PDLLA涂层螺钉生物相容性和促进新西兰大白兔股骨颈骨折愈合的作用.方法体外释放实验检测直径3.5mm载VEGF和BMP-2的PDLLA涂层钛合金螺钉的VEGF和BMP-2的释药能力,提取涂层浸提液行体内全身急性毒性检测、热原反应、溶血实验和体外细胞毒性实验.12只体质量2.5 ~3.9kg健康成熟新西兰大白兔双侧股骨颈骨折,右侧以载VEGF和BMP-2的PDLLA涂层螺钉固定,左侧以无涂层螺钉固定行自身对照.术后12周进行X线、micro-CT和组织学分析.结果 VEGF和BMP-2在最初8h内释放剧增,随后持续和稳定释放12周.全身急性毒性检测、热原反应、溶血实验和细胞毒性实验符合GB/T 16886和ISO 10993标准.术后12周,右侧骨折已愈合,左侧对照尚未愈合.右侧微血管数目、骨密度、骨体积分数、骨小梁厚度和数目较左侧明显增加(P<0.01),骨小梁间距较左侧降低(P<0.01).结论载VEGF和BMP-2的PDLLA涂层螺钉生物相容性好,持续稳定释放VEGF和BMP-2促进股骨颈骨折愈合.

Objective To assess the biocompatibility of PDLLA coating screw carrying vascular endothelial growth factor( VEGF) and Bone morphogenetic protein 2( BMP - 2) and explore the treatment of the coating screw on femoral neck fracture in rabbits. Methods PDLLA coated titanium alloy screws with 3. 5mm diameters carrying VEGF and BMP - 2 were prepared and received in vitro release experiment to evaluate the amounts of VEGF and BMP - 2. The coating extracts underwent in vivo systemic acute toxicity test, pyrogen test, hemolysis test and in vitro cytotoxicity test. Bilateral femoral neck fracture were made in the 12 healthy mature New Zealand white rabbits weighed 2. 5 -3. 9kg. The right femoral neck fracture was fixed with the PDLLA coating screws carrying VEGF and BMP - 2. The left was fixed with the screws without coating. At the end of the 12th week , all rabbits were euthanasized and received X - ray, Micro - CT and histological study. Results VEGF and BMP - 2 were significantly released in the initial 8 hours, and then were releasing continuously and stably in the next 12 weeks. The results of in vivo systemic acute toxicity test, pyrogen test, hemolysis test and in vitro cytotoxicity test met GB/T 16886 and ISO 10993 standard. At the end of the 12th week, the right femoral neck fractures healed and the left did not. The number of microvessel, bone mineral density, BV/TV , Tb. Th and Tb. N in the right were higher than those in the left( P<0.01 ). Tb. Sp in the right were lower than that in the left ( P <0.01). Conclusion The PDLLA coating screw carrying VEGF and BMP - 2 showed excellent biocompatibility. VEGF and BMP -2 were releasing continuously in the 12 weeks, which accelerated the fracture healing of femoral neck.