北京生物医学工程

３Ｄ打印多孔 β－ＴＣＰ负载ＶＡＮ／ＰＬＧＡ缓释微球复合支架的表征评价

Characterization and evaluation of 3D printed porous β-TCP scaffolds loaded with VAN/PLGA microsphere scaffold

作者：王建范江伟陈洪涛

单位：新疆医科大学第六附属医院创伤骨科（乌鲁木齐 830092）<br />通信作者：陈洪涛。E-mail：ansus@sina.com

分类号：R318.08 

出版年·卷·期（页码）：2022·41·5（471-476）

摘要：

目的通过对多孔β-磷酸三钙（tricalcium phosphate，TCP）负载万古霉素/聚乳酸-羟基乙酸（vancomycin/poly lactic co glycolic acid， VAN/PLGA）缓释微球复合支架进行表征评价，初步判断其能否能作为修复骨缺损的材料。方法利用CAD软件绘制多孔β-TCP支架，由3D打印机打印制作，再经马弗炉干燥制成β-TCP骨组织支架。采用W/O/W法制备VAN/PLGA缓释微球，将β-TCP骨支架与VAN/PLGA微球悬液震荡混匀，使微球吸附到支架的微孔内，离心冻干后即得β-TCP负载VAN/PLGA缓释微球复合支架。从支架外观形态、孔隙率、药物缓释率、力学性能和体外降解实验等多方面进行表征评价。结果β-TCP负载VAN/PLGA缓释微球复合支架呈白色立方体状，表面附着有一层大小均匀的圆形颗粒，在光镜下能清楚地看到内部结构；通过液体置换法测量得β-TCP负载VAN/PLGA复合支架的平均孔隙率为（59.21±1.55）%，小于3D打印β-TCP空白支架的65.27±2.37（t=2.552，P=0.032）；根据VAN 标准曲线测得VAN/PLGA微球对VAN的药物负载率为（17.42±1.85）%，包封率为（35.13±3.59）%；体外药物释放实验表明，β-TCP负载VAN/PLGA复合支架在24 d时释放率可达50%，还可以进一步释放，在体内能保持长时间的抑菌抗感染效果；力学性能结果显示，复合支架最大负荷为（174.50±7.80）N，最大强度为（4.83±0.25）MPa；体外降解实验说明，与β-TCP空白支架相比，负载VAN/PLGA的复合β-TCP支架在体内降解时间更长，在20 W时才能降解完全，对骨缺损能起到长久的修复作用。结论3D打印多孔β-TCP负载VAN/PLGA缓释微球复合支架具有良好的缓释性能、力学性能和抗感染修复功能，可作为修复骨缺损的优良材料。

Objective Through the characterization evaluation of porous β-（tricalcium phosphate）TCP loaded vancomycin/poly lactic co glycolic acid （VAN/PLGA） sustained-release microspheres composite scaffold designed and manufactured, it is preliminatively determined whether it can be used as a material for repairing bone defects. Methods The porous β-TCP scaffold was drawn by CAD software, printed by 3D printer, and then dried in muff furnace to form β-TCP bone tissue scaffold. VAN/PLGA sustained-release microspheres were prepared by W/O/W method. The β-TCP bone scaffold and VAN/PLGA microspheres suspension were mixed by shaking, and the microspheres were adsorbed into the micropores of the scaffold. After centrifugation and lyophilization, the β-TCP loaded VAN/PLGA sustained-release microspheres composite scaffold was obtained. The scaffolds were characterized by morphology, porosity, sustained drug release rate, mechanical properties and in vitro degradation experiments. Results β-TCP loaded VAN/PLGA sustained-release microspheres composite scaffold was white cube shape, with a layer of uniform size of circular particles attached to the surface, and the internal structure could be clearly seen under the light microscope. The average porosity of β-TCP loaded VAN/PLGA composite scaffold measured by liquid replacement method was （59.21±1.55）%, which was smaller than 65.27±2.37 (t=2.552, P=0.032) of β-TCP blank scaffold. According to VAN standard curve, VAN loading rate and encapsulation rate of VAN/PLGA microspheres were (17.42±1.85) % and (35.13±3.59) % respectively. In vitro drug release experiments showed that the release rate of β-TCP loaded VAN/ PLGA composite scaffold could reach 50% after 24 days, and it could be further released, which could maintain the antibacterial and anti infective effect for a long time. The mechanical performance results show that the maximum load of the composite bracket was (174.50±7.80)N, and the maximum strength was (4.83±0.25)MPa. In vitro degradation experiment showed that compared with β-TCP blank scaffold, the degradation time of compound β-TCP scaffold loaded with VAN/PLGA was longer in vivo, and the degradation was complete at 20W, which could play a long-term role in the repair of bone defects. Conclusions The 3D printed porous β-TCP loaded VAN/PLGA sustained-release microsphere composite scaffold has good sustained-release performance, mechanical properties and anti-infective repair function, which can be used as an excellent material to repair bone defects.

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