重庆医科大学药学院,重庆医科大学药学院,重庆医科大学药学院,重庆医科大学药学院
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(cstc2017jcyjAX0029),重庆市教委科技项目(KJ1702035)和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)
chongqing medical university,chongqing medical university,chongqing medical university,chongqing medical university
This work was supported by grants from The National Natural Science Foundation of China (81401535), Fundamental and Advanced Research Projects of Chongqing City (cstc2017jcyjAX0029), Science and Technology Research Project of Chongqing Education Commission (KJ1702035), Research Project of Fujian Provincial Key Laboratory of Biochemical Technology (z17x0003)
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6~10 μm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100~200 μm,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.
Abstract 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 100-200 μm, 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.
白燕,白丽娟,陈华黎,周静.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[J].生物化学与生物物理进展,2018,45(1):68-78
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