Henry Jeffrey J D, Yu Jian, Wang Aijun, Lee Randall, Fang Jun, Li Song
Department of Bioengineering, University of California, Berkeley, CA 94720, United States of America. UC Berkeley and UCSF Bioengineering Graduate Program, Berkeley, CA94720, United States of America.
Biofabrication. 2017 Aug 17;9(3):035007. doi: 10.1088/1758-5090/aa834b.
Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.
合成小口径血管移植物的失败率很高，而内皮化对于预防血栓形成和移植物闭塞至关重要。一种有前景的方法是原位组织工程，即植入无细胞支架并提供刺激信号以引导原位重塑为功能性血管。理想的支架应具有足够的生物分子固定结合位点以及与天然组织相似的机械性能。在此，我们开发了一种在静电纺丝过程中混合低分子量（LMW）弹性聚合物的新方法，以增加结合位点并改善血管移植物的机械性能。LMW弹性聚合物改善了支架的弹性，并显著增加了与微/纳米纤维支架结合的肝素量，这反过来又增加了血管内皮生长因子（VEGF）的负载能力并延长了VEGF的释放时间。将血管移植物植入大鼠颈动脉以评估其体内性能。VEGF处理显著增强了内皮形成和血管移植物的整体通畅性。肝素涂层还增加了细胞向静电纺丝移植物中的浸润，从而增加了移植物壁内胶原蛋白和弹性蛋白的产生。这项工作表明，LMW弹性聚合物混合是一种用于原位血管组织工程的微/纳米纤维血管移植物机械和生物学性能工程化方法。
