Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique.
Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique.
复制标题
双相分离技术制备具有改善生物降解性和平滑肌细胞浸润的大孔纳米纤维血管支架
DOI：
10.2147/ijn.s183463
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发表时间：
2018
影响因子：
8
通讯作者：
He C
中科院分区：
文献类型：
--
作者：
Wang W;Nie W;Liu D;Du H;Zhou X;Chen L;Wang H;Mo X;Li L;He C
血管移植物的快速降解和平滑肌细胞（SMCs）的浸润被认为是新生血管功能再生的关键。本研究开发了一种新的双相分离技术，通过相分离非混相聚合物共混物，一锅法制备了大孔纳米纤维聚l -乳酸(PLLA)/聚ε-己内酯（PCL）血管支架。然而，PLLA/PCL的缓慢降解限制了细胞的浸润。在此，我们假设聚乳酸-羟基乙酸（PLGA）可以与PLLA混溶，但与PCL不混溶。然后，将PLGA引入PLLA/PCL共混物中，采用双相分离技术制备生物降解性提高的大孔纳米纤维支架。材料与方法研究了PLGA与PLLA、PCL的混相性。然后，采用双相分离技术制备PLLA/PLGA/PCL支架。对制备的支架进行形态学、体外降解、力学性能、细胞对人血管间充质干细胞（HVSMCs）的浸润和活力等方面的表征。最后，将血小板衍生生长因子- bb （PDGF-BB）固定在支架上，研究其对HVSMCs生物活性的影响。结果PLGA可与PLLA混溶，但与PCL不混溶。PLGA的加入增大了复合支架的孔径，提高了复合支架的生物降解性。值得注意的是，混合比例为30:40:30的PLLA/PLGA/PCL支架具有更好的孔隙连通性和足够的力学性能。此外，HVSMCs能够在纳米纤维支架中生长和浸润，PDGF-BB对纳米纤维支架进行表面修饰，增强了HVSMCs的迁移和增殖。结论本研究为将双相分离技术扩展为利用三元均匀聚合物共混制备物理化学性能更好的大孔纳米纤维支架提供了一种策略。所制备的PLLA/PLGA/PCL支架可望用于血管组织工程中功能膜介质的再生。
Introduction The fast degradation of vascular graft and the infiltration of smooth muscle cells (SMCs) into the vascular graft are considered to be critical for the regeneration of functional neo-vessels. In our previous study, a novel dual phase separation technique was developed to one-pot prepare macroporous nanofibrous poly(L-lactic acid) (PLLA)/poly(ε-caprolactone) (PCL) vascular scaffold by phase separating the immiscible polymer blend. However, the slow degradation of PLLA/PCL limited cell infiltration. Herein, we hypothesized that poly(lactic-co-glycolic acid) (PLGA) would be miscible with PLLA but immiscible with PCL. Then, PLGA can be introduced into the PLLA/PCL blend to fabricate macroporous nanofibrous scaffold with improved biodegradability by using dual phase separation technique. Materials and methods The miscibility of PLGA with PLLA and PCL was evaluated. Then, the PLLA/PLGA/PCL scaffold was prepared by dual phase separation technique. The prepared scaffolds were characterized in terms of the morphology, in vitro degradation, mechanical properties, and cells’ infiltration and viability for human vascular SMCs (HVSMCs). Finally, platelet-derived growth factor-BB (PDGF-BB) was immobilized on the scaffold and its effect on the bioactivity of HVSMCs was studied. Results PLGA is miscible with PLLA but immiscible with PCL as hypothesized. The addition of PLGA enlarged the pore size and improved the biodegradability of composite scaffold. Notably, PLLA/PLGA/PCL scaffold with the blend ratio of 30:40:30 possessed improved pore interconnectivity for cells’ infiltration and enough mechanical properties. Moreover, HVSMCs could grow and infiltrate into this scaffold, and surface modification with PDGF-BB on the nanofibrous scaffold enhanced HVSMCs migration and proliferation. Conclusion This study provides a strategy to expand dual phase separation technique into utilizing ternary even multinary polymer blend to fabricate macroporous nanofibrous scaffold with improved physicochemical properties. The prepared PLLA/PLGA/PCL scaffold would be promising for the regeneration of functional tunica media in vascular tissue engineering.