快速成型技术构建胶原丝素仿生骨支架治疗大鼠股骨髁缺损

摘要

Objective To explore the feasibility and effect of 3D printing bionic bone scaffold constructed collagen–silk protein in bone defect of mice. Methods Collagen protein,silk protein,and hydroxyapatite were chosen as raw material. The bone defect shape of scaffold was designed by computer assisted designed software SolidWorks 2015 and combined with cryodrying 3D printing and the biomechanical property was evaluated. Micro-structure of scaffold was scanned by electron microscope;Strain,stress and E-modular when material compression to 10% was tested by bio-mechanical machine;cell growth situation of cocultivation between MC3T3-E1 and bionic bone scaffold was tested in different time-point. Mice bone defect was constructed and filled by bionic bone scaffold,then scanned the histologi-cal situation in 2,8 and 12 weeks. Results The structure of bionic scaffold was cascading-porous-spatial. The di-ameter of big hole,micro hole and wall thickness were moderately. High porosity was benefit for penetration of nutri-ents. For biomechanical attribute,average compression displacement was (867.48 ± 0.28) μm, average stress was (0.071 ± 0.006) MPa,The average E-modulus of bone scaffold was(361.47 ± 42.83) MPa. For cocultivation,ap-propriate cell compatibility was suitable for cell adhesion and growth. Majority of mice bone defect could be treated within 12 weenks. Conclusions Collagen-silk protein scaffold constructed by 3D printing has stable physical proper-ties,appropriate cell compatibility and obvious curative effect in bone defect, which establish a solid foundation in solving bone defect.%目的 探讨快速成型技术构建胶原丝素仿生骨支架的可行性,评估该骨支架治疗大鼠股骨髁缺损的效果.方法 选取胶原蛋白、丝素蛋白和羟基磷灰石粉为原材料,根据骨缺损形状利用SolidWorks 2015软件设计仿生骨支架外形,结合低温干燥快速成型技术构建仿生骨支架,并评估该支架在大鼠体内外的性能.扫描电镜观察骨支架超微结构;力学测试机评估支架试件压至10%应变时平均压缩位移、平均应力和杨氏模量.小鼠胚胎成骨前体细胞(MC3T3-E1)与该仿生骨支架共培养,观察支架孔隙内不同时间点细胞生长情况.制作大鼠股骨髁骨缺损模型,并用仿生骨支架适量填充,于第2、8、12周观察局部组织病理学变化.结果 仿生骨支架整体结构为层叠-多孔-立体结构,壁厚、大孔和微细小孔直径适中,孔隙率高达94.38%,利于营养物质的渗入.力学性能指标中平均压缩位移量为(867.48 ± 0.28)μm,平均应力为(0.071 ± 0.006)MPa,平均仿生骨杨氏模量为(361.47 ± 42.83)MPa.MC3T3-E1细胞与该支架共培养的组织相容性好,利于细胞的黏附和生长.大鼠骨缺损体内实验显示,仿生骨支架在12周内可基本完成缺损修复,效果显著.结论 快速成型技术构建的胶原丝素仿生骨支架性质稳定、细胞相容性良好,治疗大鼠骨缺损效果显著,为临床解决骨缺损难题奠定了基础.