掺铕聚磷酸钙骨组织工程支架可促成骨、血管生成及抗无菌性松动  

Osteogenesis,angiogenesis and anti-aseptic loosening of europium-doped calcium polyphosphate bone tissue engineering scaffold

作　　者：吴羽翀 彭旭[2] 余喜讯[1] Wu Yuchong;Peng Xu;Yu Xixun(College of Polymer Science and Engineering,Sichuan University,Chengdu 610065,Sichuan Province,China;Laboratory Animal Center,Sichuan University,Chengdu 610065,Sichuan Province,China)

机构地区：[1]四川大学高分子科学与工程学院,四川省成都市610065 [2]四川大学动物实验中心,四川省成都市610065

出　　处：《中国组织工程研究》2022年第28期4458-4465,共8页Chinese Journal of Tissue Engineering Research

基　　金：四川省重点研发计划(2019YFS0121),项目负责人:余喜讯。

摘　　要：背景:骨缺损修复的临床成功不仅取决于成骨作用,还与血管生成以及抑制骨吸收能力密切相关。因此,开发具有多种功能的生物支架材料尤为重要。目的:通过微量元素掺杂的方式改善传统骨修复材料所存在的力学强度低、促血管能力不强、骨诱导能力不足等多种问题。方法:通过高温烧结法将不同摩尔含量的铕(0%,1%,3%,5%和7%)掺入聚磷酸钙支架中,制备出多孔掺铕聚磷酸钙支架。采用红外光谱、X射线衍射分析、X射线光电子能谱分析、扫描电镜、压汞法和抗压强度测试等分析方法分别对其结构、晶型、元素组成、孔径分布及力学性能等进行表征分析。将各组支架分别与小鼠胚胎成骨细胞前体细胞和人脐静脉内皮细胞共培养,并通过细胞增殖检测、扫描电镜、激光扫描共聚焦显微镜、酶联免疫吸附法等测试对其生物学性能进行综合评估。结果与结论:①铕的掺杂并没有改变聚磷酸钙的主链结构及其β晶型,但可将孔径分布稳定在200-400μm内,以利于骨骼长入。②与纯聚磷酸钙支架相比,掺铕聚磷酸钙支架的晶粒结合更紧密且排列更有序,材料的机械强度显著提升。③掺铕聚磷酸钙支架表面粗糙度有利于细胞的黏附和铺展,可同时促进小鼠胚胎成骨细胞前体细胞和人脐静脉内皮细胞在支架表面的生长和增殖,其中以5%掺铕聚磷酸钙组最明显。④掺铕聚磷酸钙支架可明显刺激材料上小鼠胚胎成骨细胞前体细胞分泌碱性磷酸酶与骨桥蛋白,以及人脐静脉内皮细胞分泌血管内皮生长因子与基质金属蛋白酶9,有利于成骨细胞的增殖分化,其中以5%掺铕聚磷酸钙组最明显。⑤5%掺铕聚磷酸钙可显著上调由成骨细胞分泌的骨保护素/核因子κB受体活化因子配体比例,表现出抑制骨溶解的潜力,可起到防治无菌性松动的作用。⑥结果表明,5%掺铕聚磷酸钙支架具有加速血管生成BACKGROUND:The clinical success of bone grafts depends not only on osteogenesis,but also on angiogenesis,and the ability to inhibit osteoclast-mediated bone resorption.Therefore,it is particularly important to develop bio-scaffold materials with multiple functions.OBJECTIVE:To improve various problems of traditional bone repair materials,such as low mechanical strength,poor vascular promoting ability,and insufficient osteoinductive ability through the doping of trace elements.METHODS:A series dose of Eu(0%,1%,3%,5%and 7%,molar ratio)was incorporated into calcium polyphosphate scaffolds by high temperature sintering to achieve a multifunctional europium-doped calcium polyphosphate.Infrared spectroscopy,X-ray diffraction analysis,X-ray photoelectron spectroscopy,scanning electron microscopy,mercury intrusion method and compressive strength test were used to characterize its structure,crystal form,element composition,pore size distribution,and mechanical properties.The europium-doped calcium polyphosphate scaffold was co-cultured with mouse embryonic osteoblast precursor cells and human umbilical vein endothelial cells.Biological performance was evaluated through cell proliferation detection,scanning electron microscope,laser scanning confocal microscope,and enzyme-linked immunosorbent assay.RESULTS AND CONCLUSION:(1)The doping of Eu3+did not change the main chain structure and crystal form of calcium polyphosphate,but it could stabilize the pore size distribution within 200-400μm,which was conducive to bone ingrowth.(2)Compared to pure calcium polyphosphate materials,the crystal grains of europium-doped calcium polyphosphate scaffolds were bonded more closely and ranged well-ordered,which were beneficial to improve mechanical strength of materials.(3)The surface roughness of europium-doped calcium polyphosphate scaffolds was conducive to cell adhesion and spreading.Mouse embryonic osteoblast precursor cells and human umbilical vein endothelial cells seeded on europium-doped calcium polyphosphate scaffolds presente

关 键 词：骨修复材料 掺铕聚磷酸钙 生物相容性 促进成骨 促血管化 无菌性松动 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学]