聚乳酸-羟基乙酸共聚物/硅酸钙三维多孔骨组织工程支架的构建与性能

摘要

背景：目前的聚乳酸-羟基乙酸共聚物(poly(lactic-co-glycolic acid)，PLGA)支架材料存在降解产物呈酸性、力学性能低、孔隙率低、孔径小、孔隙之间的连通率不佳、支架的几何形状不易控制等缺陷。目的：构建具有三维连通多孔结构的PLGA/硅酸钙骨组织工程支架材料，测试其体外降解性能、力学性能及生物相容性。方法：先通过乳液溶剂挥发法制备PLGA/硅酸钙多孔复合微球，3D-Bioplotter制备PLGA三维多孔支架，然后采用低温融合技术将微球与支架结合，制备PLGA/硅酸钙复合多孔支架。检测PLGA/硅酸钙多孔复合微球与PLGA微球的组成成分、形貌及降解性能，检测PLGA三维多孔支架与PLGA/硅酸钙复合多孔支架的形貌、孔隙及压缩强度。分别采用PLGA/硅酸钙多孔复合微球与PLGA微球浸提液，含PLGA三维多孔支架与PLGA/硅酸钙复合多孔支架的培养液培养小鼠骨髓间充质干细胞，1，3，5 d后检测细胞增殖活性。结果与结论：①微球形貌及降解性能：硅酸钙组分的加入，有助于PLGA微球形成表面规则孔结构和内部空腔结构，以及提高PLGA微球降解的pH值；②支架结构：PLGA/硅酸钙复合多孔支架的纤维直径与支架孔径均小于PLGA三维多孔支架；③支架孔隙：PLGA/硅酸钙复合多孔支架的孔隙率与平均孔径均小于PLGA三维多孔支架；④支架力学性能：PLGA/硅酸钙复合多孔支架的压缩强度与压缩模量高于PLGA三维多孔支架(P<0.05)；⑤细胞相容性：骨髓间充质干细胞在两种微球浸提液和两种支架上的生长状况良好；⑥结果表明：PLGA/硅酸钙复合多孔支架具有良好的体外降解性能、力学性能及生物相容性。%BACKGROUND:Some disadvantages exsist in commonly used poly(lactic-co-glycolic acid) (PLGA) scaffolds, including acidic degradation products, suboptimal mechanical properties, low pore size, poor porosity and pore connectivity rate and uncontrol able shape. OBJECTIVE:To construct a scaffold with three-dimensional (3D) pores by adding calcium silicate to improve the properties of PLGA, and then detect its degradability, mechanical properties and biocompatibility. METHODS:PLGA/calcium silicate porous composite microspheres were prepared by the emulsion-solvent evaporation method, and PLGA 3D porous scaffold was established by 3D-Bioplotter, and then PLGA/calcium silicate composite porous scaffolds were constructed by combining the microspheres with the scaffold using low temperature fusion technology. The compositions, morphology and degradability of the PLGA/calcium silicate porous composite microspheres and PLGA microspheres, as wel as the morphology, pore properties and compression strength of the PLGA 3D scaffolds and PLGA/calcium silicate composite porous scaffolds were measured, respectively. Mouse bone marrow mesenchymal stem cel s were respectively cultivated in the extracts of PLGA/calcium silicate porous composite microspheres and PLGA microspheres, and then were respectively seeded onto the PLGA 3D scaffolds and PLGA/calcium silicate composite porous scaffolds. Thereafter, the cel proliferation activity was detected at 1, 3 and 5 days. RESULTS AND CONCLUSION:Regular pores on the PLGA microspheres and internal cavities were formed, and the PH values of the degradation products were improved after adding calcium silicate. The fiber diameter, pore, porosity and average pore size of the composite porous scaffolds were al smal er than those of the PLGA scaffolds. The compression strength and elasticity modulus of the composite porous scaffolds were both higher than those of the PLGA scaffolds (P<0.05). Bone marrow mesenchymal stem cel s grew wel in above microsphere extracts and scaffolds. These results indicate that PLGA/calcium silicate composite porous scaffolds exhibit good degradability in vitro, mechanical properties and biocompatibility.