负载ZOL-GNPs的多孔钛合金支架促进OP骨缺损修复的作用机制  

Investigation on the mechanism of PDA-coated porous titanium alloy scaffold loaded with ZOL-GNPs in promoting osteoporotic bone defect restoration

作　　者：杨晓江 蒋明春 武振方 遆云帆 鲁经纬 赵建宁[1] 孙国静[1] YANG Xiao-jiang;JIANG Ming-chun;WU Zhen-fang;TI Yun-fan;LU Jing-wei;ZHAO Jian-ning;SUN Guo-jing(Department of Orthopaedics,General Hospital of Eastern Theater Command,PLA,Nanjing 210002,Jiangsu,Chi-na)

机构地区：[1]东部战区总医院(原南京军区南京总医院)骨科,南京210002

出　　处：《医学研究生学报》2022年第8期813-819,共7页Journal of Medical Postgraduates

基　　金：后勤科研课题(21XLS19);东部战区总医院博士后课题(48742)。

摘　　要：目的 骨质疏松症(OP)容易引发骨折甚至导致骨缺损的发生。文章探讨将聚多巴胺(PDA)涂层多孔钛合金支架与唑来膦酸明胶纳米微球(ZOL-GNPs)相结合,构建一种不但具有良好机械性能与生物相容性,而且可局部缓释给药抗骨质疏松(OP)的新型多孔钛合金支架。方法 基于电子束熔融技术构建负载不同浓度ZOL-GNPs的PDA涂层多孔钛合金支架(对照组:0μmol/L;实验组:1μmol/L,10μmol/L,50μmol/L,100μmol/L,500μmol/L),并对支架进行表征分析和药物释放检测。在新型支架浸提液条件下对破骨细胞进行骨吸收能力检测和凋亡检测。构建OP骨缺损模型,并通过Micro-CT扫描、组织学检测和生物力学检测评估新型支架在动物体内的效果。结果 成功构建了负载ZOL-GNPs的PDA涂层多孔钛合金支架,药物检测结果显示该新型支架在体外可保持数周稳定的ZOL释放速率。骨吸收能力检测结果显示50μmol/L组所形成骨板吸收面积明显低于对照组(P<0.01)。破骨细胞凋亡率随ZOL的浓度呈线性增加,所有实验组均明显高于对照组(P<0.01)。Micro-CT扫描显示50μmol/L组的骨生长情况明显优于其他组(P<0.01)。组织学染色显示随着ZOL浓度的升高,新生骨量逐渐增多,当ZOL浓度为50μmol/L时新骨量最大。支架植入8周和12周后,1μmol/L组、10μmol/L组和50μmol/L组的支架8周[(2.11±0.11、2.26±0.13、2.58±0.09)GPa]和12周[(2.23±0.07、2.48±0.16、2.91±0.10)GPa]弹性模量均显著高于支架植入前的弹性模量(P<0.05),并且50μmol/L组的支架弹性模量最高,接近人体松质骨弹性模量的同时,抗压性能较好。结论 成功构建了一种负载ZOL-GNPs的PDA涂层多孔钛合金支架,其具有良好的机械性能和局部药物缓释抗骨质疏松作用;当ZOL浓度为50μmol/L时更有利于OP骨缺损的修复。Objective To construct a new type of PDA-coated porous titanium alloy scaffold loaded with ZOL-GNPs, which exhibits superior match with human bone mechanical characteristics, as well as a sustainable local slow-release of anti-osteoporosis drugs. Methods We constructed PDA-coated porous titanium alloy scaffold loaded with ZOL-GNPs basing on electron beam melting technology, and studied its biomechanical properties as well as analyze the mechanism of drug release. Osteoclasts were cultured under the new porous titanium alloy scaffold extracts, and the bone resorption capacity and apoptosis detection of osteoclasts were carried out. New porous titanium alloy scaffolds were implanted into OP bone defect animal models. Micro-CT scanning, histological staining, biomechanical tests were carried out for evaluation. Results The PDA-coated porous titanium alloy scaffold loaded with ZOL-GNPs were successfully constructed, which maintained a stable drug release rate for at least several weeks in vitro. Detection of the bone resorption capacity of osteoclasts showed that at 50 μmol/L concentration, the bone plate resorption area was significantly lower than that of the control group(P<0.01). With the increase of the concentration, the apoptosis rates were increased, and all experimental groups showed significantly higher apoptosis rate than the control group(P<0.01). Micro-CT scan showed that at a ZOL concentration of 50 μmol/L, the new bone formation was significantly better than other groups. Histological examination showed that with the increase of ZOL concentration, the amount of new bone gradually was increased. The new bone ingrowth was maximum at ZOL concentration of 50 μmol/L. At 8 weeks and 12 weeks after scaffold implantation, the scaffold elastic modulus of the 50 μmol/L group was the highest, exhibiting a satisfactory compression resistance. Conclusion This study successfully constructs a PDA-coated porous titanium alloy scaffold loaded with ZOL-GNPs, which not only has good mechanical properties and biocompa

关 键 词：骨缺损 唑来膦酸 多孔钛合金支架 明胶纳米微球 破骨细胞 

分 类 号：R683[医药卫生—骨科学]