3D生物打印构建聚乳酸羟基乙酸/纳米羟基磷灰石支架骨形态发生蛋白2缓释复合体的实验研究  

3D-bioprinting manufacturing polylactic-co-glycolic acid/nano-hydroxyapatite scaffold/bone morphogenetic protein-2 sustained release composite

作　　者：臧晓龙 孙健[1] 李亚莉[1] 陈立强[1] 杨学财[1] 梁立卿 杜国庆[1] 

机构地区：[1]青岛大学附属医院口腔颌面外科,山东省青岛市266003

出　　处：《中国组织工程研究》2016年第16期2405-2411,共7页Chinese Journal of Tissue Engineering Research

基　　金：山东省自然科学基金项目(ZR2012HM069)~~

摘　　要：背景:3D生物打印技术制备的工程骨支架,其形态、结构可控性好,但对组织工程骨细胞生长因子复合体的构建及缓释细胞因子的时效、量效特点有待进一步研究。目的:应用3D生物打印技术制备聚乳酸羟基乙酸/纳米羟基磷灰石支架骨形态发生蛋白2缓释复合体,检测聚乳酸羟基乙酸/纳米羟基磷灰石支架的生物学性能和负载细胞因子缓释复合体的性能,探讨其作为组织工程骨支架复合体的可行性。方法:用壳聚糖和β-甘油磷酸钠制备温敏型壳聚糖水凝胶,负载骨形态发生蛋白2壳聚糖纳米球形成缓释复合载体,3D生物打印制备聚乳酸羟基乙酸/纳米磷灰石壳聚糖纳米骨形态发生蛋白2细胞因子缓释复合体,体外实验检测其生物学特性及缓释骨形态发生蛋白2的时效、量效特点。结果与结论:3D生物打印技术制备的聚乳酸羟基乙酸/纳米羟基磷灰石支架材料平均孔径(431.31±18.40)μm,孔隙率为(73.64±1.82)%。聚乳酸羟基乙酸/纳米羟基磷灰石复合体48 h内和第30天内蛋白累计释放率均符合生理状态缓释要求,有效控制了聚乳酸羟基乙酸/纳米羟基磷灰石缓释复合体的突释效应,缓释效果符合生物学要求。说明3D生物打印制备的聚乳酸羟基乙酸/纳米磷灰石壳聚糖纳米骨形态发生蛋白2细胞因子缓释复合体其孔隙率、孔径、缓释性能、降解速率、机械强度等指标,均符合构建组织工程骨的生物学要求。BACKGROUND： Tissue-engineered bone scaffold fabricated by 3D-bioprinting technique has good controllability in morphology and structure. However, construction of tissue-engineered bone/cell growth factor complex and time-dose effect of sustained-release factors are needed to be further researched. OBJECTIVE： To fabricate a sustained-release composite of polylactic-co-glycolic acid（PLGA）/nano-hydroxyapatite（n-HA） scaffold carrying bone morphogenetic protein-2（BMP-2） using 3D-bioprinting technique, and test the biological properties of the PLGA/n-HA scaffold carrying BMP-2 and the sustained-release properties, thereby to discuss its feasibility as the tissue-engineered bone scaffold composite. METHODS： Temperature-sensitive chitosan hydrogel was prepared using chitosan and β-glycerophosphate to construct a sustained-release composite, chitosan nanoparticles carrying BMP-2. 3D-bioprinting technique was utilized to fabricate the PLGA/n-HA scaffold carrying BMP-2. Biological features of the scaffold composite were tested, and time-dose effect of BMP-2 sustained-release was observed. RESULTS AND CONCLUSION： The average pore size of the scaffold-cytokine composite was（431.31±18.40） μm, and the porosity was（73.64±1.82）%. The cumulative release rate of BMP-2 from the scaffold-cytokine composite that effectively controlled the burst release during 48 hours and 30 days were suitable for the physiological needs. In conclusion, the porosity, pore size, release property, degradation rate, and mechanical strength of the scaffold-cytokine composite all meet the biological requirements of tissue-engineered bone construction.

关 键 词：壳聚糖 乳酸 骨形态发生蛋白质类 组织工程 生物材料 缓释材料 聚乳酸羟基乙酸/纳米羟基磷灰石 3D生物打印技术 缓释载体 支架 水凝胶 纳米球 山东省自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]