北京生物医学工程

基于高温挤出打印的PLGA/β-TCP人工骨支架制备及其性能研究

Preparation and properties of PLGA/β-TCP artificial bone scaffold based on high temperature extrusion printing

作者：史耕田马志勇钱正徐文宽王启帆

单位：宁波大学机械工程与力学学院（浙江宁波 3152110；湖州师范学院工学院(浙江湖州 313000）湖州艾先特电子科技有限公司（浙江湖州 313000）

分类号：R318.08；R318.01

出版年·卷·期（页码）：2020·39·3（264-270）

摘要：

目的制备具有较优力学性能和细胞增殖特性的聚乳酸-羟基乙酸共聚物/β-磷酸三钙[poly(lactic-co-glycolic acid) / β-tricalcium phosphate，PLGA/β-TCP]人工骨支架，为骨组织工程支架材料和结构的选择提供实验依据。方法以PLGA和纳米β-TCP为原材料，先将PLGA在加热筒中高温熔融，再将β-TCP混合搅拌均匀进行打印，采用高温挤出打印方法制备人工骨支架，研究不同材料配比(PLGA与β-TCP配比为4:1、3:1、2:1)、不同孔径(200 μm、300 μm和400 μm)、不同层高(4.2mm、5.4mm和6.6mm)以及不同孔形(方形、45°倾斜和60°倾斜)对支架力学性能和细胞增殖性能的影响。打印了9组支架，利用扫描电镜分析了支架的形貌特征，用万能材料试验机测试了支架的抗压强度、弹性模量，用CCK-8试剂盒进行了细胞增殖性能测试。最后对实验数据进行极差分析，得出最优组合，并制作相应的支架，进行力学性能和生物性能的测试。结果在力学性能实验中，S5组支架显示出最好的抗压强度（7.23 MPa），S9组支架显示出最好的杨氏模量（356.1 MPa），与骨小梁相当；在细胞增殖实验中，S1组支架显示出最好的增殖特性。通过正交实验法，分析并实验验证，得出综合性能最优的支架参数为材料配比为4:1、层高为6.6 mm、孔型为45°倾斜以及孔径为200μm。结论材料配比为4:1、层高为6.6 mm、孔型为45°倾斜以及孔径为200μm的支架基本能够满足某些松质骨（如骨小梁）的力学性能和细胞增殖性能，并可为后续相关研究提供实验和理论基础。

Objective To obtain poly(lactic-co-glycolic acid) / β-tricalcium phosphate (PLGA/β-TCP )artificial bone scaffolds with superior mechanical and cell proliferation characteristics under different structures and materials ratios through orthogonal experiment. The high temperature extrusion printing method is used to provide an experimental basis for the preparation of selection of bone tissue engineering scaffold materials and structures with sufficient mechanical properties and good biological properties. Methods Poly(lactic-co-glycolic acid) (PLGA) and nano-β-tricalcium phosphate (β-TCP) were used as the source materials. The PLGA was first melted in a heating cylinder at a high temperature, and the β-TCP was uniformly mixed and printed. Artificial bone scaffolds were preparated by high-temperature extrusion printing method, and we studied the impact of ratio of different materials (PLGA and β-TCP ratio is 4:1, 3:1, 2:1), different pore sizes (200μm, 300μm and 400μm), different layer height effects of (4.2 mm, 5.4 mm, and 6.6 mm) and different hole shapes (square 45°, and 60° tilt) on mechanics and cell proliferation performance. Nine groups of scaffold were printed. The morphology of the scaffolds was analyzed by scanning electron microscopy. The compressive strength, elastic modulus of the scaffolds were tested by universal materials testing machine，and cell proliferation comprehensive performance was tested by CCK-8. Finally, the experimental data were range analyzed. The range analysis gived the optimal combination and scaffolds of the parameters obtained from the data analysis were fabricated ，it was tested for mechanical properties and biological properties. Results In the mechanical properties experiment, the S5 group showed the best compressive strength (7.23 MPa), and the S9 group showed the best Young's modulus (356.1 MPa), which was comparable to the trabecular bone; In cell proliferation experiments, the S1 group showed the best proliferation characteristics. Through orthogonal experiment, analysis and experimental verification, the optimal scaffold performance parameters were ratio of 4:1 of PLGA and β-TCP , layer height 6.6mm, hole shape 45°tilt and pore size 200μm. Conclusions The scaffolds with a material ratio of 4:1, a layer height of 6.6 mm, a pore shape of 45° inclination, and a pore diameter of 200 μm have an optimum mechanical and cell proliferation comprehensive performance，which provide a better scaffold that can basically meet certain the mechanical properties and cell proliferation properties of some cancellous bones (eg, trabecular bone), and provide experimental and theoretical basis for subsequent related research.

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