多孔磷酸钙/骨基质明胶复合骨水泥的构建及理化特性  

Development and physicochemical characterization of a porous calcium phosphate/bone matrix gelatin composite cement

作　　者：王松 杨函 杨剑 张开权 康建平 王清 Wang Song;Yang Han;Yang Jian;Zhang Kaiquan;Kang Jianping;Wang Qing(The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China)

机构地区：[1]西南医科大学附属医院,四川省泸州市646000

出　　处：《中国组织工程研究》2018年第34期5419-5425,共7页Chinese Journal of Tissue Engineering Research

基　　金：泸州-川医大联合课题(2015LZCYD-S05);四川省教育厅科研课题(18ZA05193D)~~

摘　　要：背景:磷酸钙骨水泥具有良好的生物相容性和骨传导性及可降解性,可用于修复骨缺损,但单一的磷酸钙骨水泥脆性大,不具有骨诱导活性,生物活性差。目的:构建多孔磷酸钙/骨基质明胶复合骨水泥,分析其理化特性。方法:提取兔骨基质明胶,制作聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic) acid,PLGA]空白微球,将PLGA微球(质量分数分别为0,5%,10%,对应制作的骨水泥分别设为空白组、5%组、10%组)、骨基质明胶与磷酸钙骨水泥复合,构建多孔磷酸钙/骨基质明胶复合骨水泥,考察3种复合骨水泥的微观结构、凝固时间、可注射性、抗溃散性、孔隙率及降解特性。将骨髓间充质干细胞分别与3种复合骨水泥浸提液共培养,14 d内检测细胞增殖率。将3种复合骨水泥材料分别植入新西兰兔腰椎椎体骨缺损内,12周后采用Micro-CT分析材料对骨缺损的修复作用。结果与结论:(1)与空白组比较,5%组、10%组复合骨水泥凝固时间减少(P <0.05),孔隙率增大(P <0.05),抗压强度、弹性模量降低(P <0.05),可注射性变差,抗扩散性弱,体外降解加速;与5%组比较,10%组复合骨水泥凝固时间减少(P <0.05),孔隙率增大(P <0.05),抗压强度、弹性模量降低(P <0.05),抗扩散性弱,体外降解加速;(2)与空白组复合骨水泥比较,5%组、10%组复合骨水泥可促进骨髓间充质干细胞的增殖(P <0.05);(3)3种骨水泥材料植入12周后的Micro-CT显示,骨缺损处均有新骨生成,5%组、10%组兔骨缺损部位骨密度、骨体积分数、骨小梁厚度、骨小梁数量均明显高于空白组(P <0.05),骨小梁分离度均低于空白组(P <0.05);(4)结果表明质量分数为5%PLGA微球与骨基质明胶、磷酸钙骨水泥复合构建的骨水泥,具有良好的力学强度、降解性能、可操作性、细胞相容性及骨诱导活性。BACKGROUND:Calcium phosphate cement has good biocompatibility,osteoinductive activity and biodegradability,which meets some of the needs for repairing bone defects.However,single calcium phosphate cement is brittle and has poor biological activity without osteoinductive activity.OBJECTIVE:To develop porous calcium phosphate/bone matrix gelatin composite cements and to explore the physicochemical characterization.METHODS:Bone matrix gelatin was extracted from rabbits and poly(lactic-co-glycolic)acid(PLGA)microspheres were prepared.The new porous cement was developed using calcium phosphate cement composited with bone matrix gelatin and PLGA microspheres.The composited cement was then divided into three groups including blank group,5%microsphere group and 10%microsphere group.Then,the physicochemical characterizations of the new porous composite bone cement in different groups were assessed by microstructure,setting time,injectability,resistance to collapsibility,in vitro degradation and porosity.Bone marrow mesenchymal stem cells were co-cultured with the extracts of these three kinds of composite cements,and cell proliferation rate was detected within 14 days of co-culture.The three kinds of composite cements were implanted into the lumbar vertebral bone defects in the rabbit model,and bone defect repair was analyzed by Micro-CT at 12 weeks after implantation.RESULTS AND CONCLUSION:With the increasing ratio of the microsphere,the setting time was shortened(P<0.05),the porosity was increased(P<0.05),the compressive strength and elastic modulus were reduced(P<0.05),the injectability and anti-diffusivity were weakened,and the in vitro degradation was fastened.Compared with the blank group,the cell proliferation was significantly increased in the 5%and 10%microsphere groups(P<0.05).At 12 weeks after implantation,Micro-CT findings revealed new bone tissues formed at the bone defect site.Compared with the blank group,significantly increased bone mineral density,bone volume fraction,trabecular thickness,and trabecular n

关 键 词：磷酸钙骨水泥 骨基质明胶 PLGA微球 复合骨水泥 理化特性 生物材料 磷酸钙类 多孔性 骨基质 组织工程 

分 类 号：R318[医药卫生—生物医学工程]