超临界流体发泡技术制备含PLLA缓释微球nHA/PLGA复合支架及体外释放性能研究

Release Performance in Vitro of nHA/PLGA Scaffolds Contained with Protein Sustained-Release PLLA Microspheres Prepared by Means of Supercritical Fluid Foaming Technology

摘要: 本研究以胰蛋白酶(Try)为模型蛋白，将蛋白缓释微球与可降解多孔支架相结合，构建在骨修复不同阶段可控释放不同生长因子的组织工程支架。首先制备胰蛋白酶-聚乳酸微球(Try-PLLAms，ms：微球)，然后复合到纳米羟基磷灰石/聚乳酸–羟基乙酸(nHA/PLGA)中，通过超临界流体发泡制备含蛋白缓释微球的多孔支架。结果表明，制备的Try-PLLAms形态良好，呈规则球形，粒径集中分布在2~7 μm，蛋白包封率为80.5%，载药量为0.89%。制备的Try-PLLAms/nHA/PLGA复合支架孔径为150~300 μm，孔隙率为50.9%~76.8%，压缩强度3.9~5.1 MPa，8周降解率为19.8%。Try-nHA/PLGA支架及Try-PLLAms微球48小时Try累积释放量达分别为85%和65.2%，而复合支架Try 48小时累积释放量为32.9%，21天累积释放量为60.6%。Try-PLLAms/nHA/PLGA复合支架的抗压强度和释放规律合适，对蛋白类药物具有良好的缓释作用，有望作为具有蛋白类药物缓释功能的组织工程支架。

Abstract: In order to construct a bone regeneration system that different cell factors controlled release at proper stage, Trypsin (Try) was selected as the model protein, and the composite of sustained-release microspheres and biodegradable porous scaffolds was prepared in this study. First of all, Try loaded poly-l-lactic acid microspheres (Try-PLLAms) were prepared, and then compounded to the nano hydroxyapatite/poly lactic-co-glycolic acid (nHA/PLGA) to build a scaffold that can release growth factors sequentially. The results showed that the Try-PLLAms were spherical shape with diameters of 2 - 7 μm. The encapsulation efficiency of the Try in PLLAms was 80.5%, and the loading capacity was 0.89%. The prepared Try-PLLAms/nHA/PLGA scaffold possessed 150 - 300 μm pore diameter, 50.9% - 76.8% porosity, 3.9 - 5.1 MPa compressive strength, and 19.8% degradation at 8 weeks. The cumulative releases of Try from Try- nHA/PLGA scaffolds and from Try-PLLAms were respectively about 85% and 65.2% at 48 hours, and that from Try-PLLAms/nHA/ PLGA scaffolds were 32.9% at 48 hours and 60.6% at 21 days. The results demonstrated that Try-PLLAms/nHA/PLGA scaffolds had excellent drug release performance with suitable compressive strength, which would be used as tissue engineering scaffolds with protein delivery.