超临界流体发泡技术制备BMP-2-PLLAms/FGF-2-nHA/PLGA复合支架及体外成骨诱导效应研究  

Study of BMP-2-PLLAms/FGF-2-nHA/PLGA Scaffolds Prepared by Supercritical Fluid Foaming Technique and The Osteogenic Induction Effects in vitro

作　　者：白燕[1] 白丽娟 陈华黎[1] 周静[1] 

机构地区：[1]重庆医科大学药学院,重庆400016

出　　处：《生物化学与生物物理进展》2018年第1期68-78,共11页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(81401535);重庆市教委基础科学与前沿技术研究一般项目(cstc2017jcyj AX0029);重庆市教委科技项目(KJ1702035);福建省生物化工技术重点实验室开放研究课题资助项目(z17x0003)~~

摘　　要：本研究将左旋聚乳酸微球(PLLAms)与纳米羟基磷灰石/聚乳酸-羟基乙醇酸(nHA/PLGA)多孔支架复合,构建可次第释放不同生长因子的骨组织工程支架.首先,制备载骨形态发生蛋白2的左旋聚乳酸微球(BMP-2-PLLAms),然后将微球与nHA/PLGA及碱性成纤维细胞生长因子2(FGF-2)按照一定的比例混合,通过超临界流体发泡制备BMP-2-PLLAms/FGF-2-nHA/PLGA复合支架.制备的BMP-2-PLLA载药微球呈规则球形,粒径分布在6~10μm之间,BMP-2载药量为1.45×10-3%,包封率为61.9%,制备的BMP-2-PLLAms/FGF-2-nHA/PLGA复合支架孔径为100~200μm,孔隙率为75.8%,抗压强度为6.8 MPa,8周降解率为19.9%.7天时,FGF-2和BMP-2的累计释放率分别为77.1%和44.2%;14天时,FGF-2和BMP-2的累计释放率分别为84.9%和61.5%.大鼠骨髓间充质干细胞(BMSCs)的成骨诱导实验证明复合支架中释放的BMP-2和FGF-2能够持续有效地刺激BMSCs的增殖和分化,具有良好的生物活性.BMP-2-PLLAms/FGF-2-nHA/PLGA复合支架有效实现了FGF-2和BMP-2的次第释放,且能够显著地促进BMSCs的成骨分化.In order to construct a bone tissue engineering scaffold that could sequentially release multiple growth factors, the released system combining of PLLA microspheres and nHA/PLGA porous scaffolds was prepared in this study. Firstly, BMP-2 was encapsulated into PLLA microspheres to prepare the BMP-2-PLLA microspheres, then BMP-2-PLLA microspheres, nHA/PLGA and FGF-2 freeze-dried powder were mixed according to a certain proportion to prepare the BMP-2-PLLAms/FGF-2-nHA/PLGA scaffolds by supercritical fluid foaming technique. The results indicated that the BMP-2-PLLA microspheres were spherical, and the particle size of BMP-2-PLLA microspheres ranged from 6 to 10 μm. The drug loading and encapsulation efficiency of BMP-2-PLLA microspheres was 1.45 × 10-3% and 61.9%, respectively. BMP-2-PLLAms/FGF-2-nHA/PLGA composite scaffolds were obtained with the pore size of 100-200μm, the porosity of 75.8%, the compressive strength of 6.8 MPa, and the degradation rate of 19.9% at 8 weeks. The cumulative releases of FGF-2 and BMP-2 from the scaffolds were respectively about 77.1% and 44.2% after 7 days, 84.9% and 61.5% after 14 days. The results of BMSCs proliferation and differentiation showed that FGF-2 and BMP-2 released from the composite scaffolds could significantly promote cell proliferation and differentiation, and present a high bioactivity. BMP-2-PLLAms/FGF-2-nHA/PLGA scaffolds realized the sequential delivery of BMP-2 and FGF-2, and could induce BMSCs proliferation and differentiation effectively.

关 键 词：左旋聚乳酸 聚乳酸-羟基乙醇酸 超临界流体发泡技术 复合支架 次第释放 成骨诱导 

分 类 号：R318[医药卫生—生物医学工程] Q813[医药卫生—基础医学]