以同轴静电纺丝技术制备壳-芯结构药物纳米纤维复合人工血管的研究

Blood vessel transplantation is the most commonly used method for treating heart and vascular disease. Although synthetic grafts have been developed, replacement of vessels with synthesized grafts often leads to the failure of such graft, especially in the grafts less than 6 mm in diameter, mainly due to restenosis, thrombopoiesis, and burst. To overcome those limitations, proper mechanical properties, adequated drug loading, as well as rapid endothelialization along the lumen of grafts are intended. Here, we develop a biocompatible nanofiber with poly(L-lactide) (PLLA)/ Polyvinyl alcohol (PVA) can be prepared by using coaxial electrospinning technique, with controlled heparin release loaded in core-shell nanofibers. The graft has circumferentially aligned PLLA fibers in the inner surface for cell growth regulation, with a random layout of PLLA fibers as media layer and has a PDMS coating for a better compressive property. Human bone mesenchymal stem cells (hBMSCs) are seeded onto the surface of the scaffolds to create an endothelial layer. The objective of this project is to acquire the engineered blood vessel with mechanical properties compatible with the native arteries. The presence and last release of MiR-126 and heparin can promote angiogenesis and prevent blood coagulation on the scaffold surface in a long-term, which make it promising application in vascular tissue engineering. The vascular grafts were evaluated in the rat abdominal aorta replacement model. This study provides a basis for the preparation of small-caliber artificial blood vessels and its application in many diseases such as angionecrosis and arteriosclerosis.

人工血管的移植常用于心脏及周围血管疾病的治疗。小口径血管移植常会因为血栓形成等导致移植失败。合适的机械性能、防止血栓形成以及在血管内表面的快速内皮化是人工血管制备的重要条件。本研究中，我们利用同轴静电纺丝技术制备聚（L-丙交酯）/聚乙烯醇壳芯结构的纳米纤维，并负载可长期缓慢释放的miR-126和肝素以促进血管再生和防止血栓的形成。由该纳米纤维构成的人工血管具有三层结构，最内层是高取向度的壳-芯纳米纤维；第二层为自由排列的纳米纤维，以增强血管的力学性能；最外面是聚二甲基硅氧烷涂层以获得更好的密封性和力学性能。在此基础上，将人骨髓间充质干细胞接种到血管支架表面并诱导其向内皮细胞分化，在缓慢释放的miR-126和肝素作用下，以期促进血管再生和防止血栓形成。最后，通过置换大鼠腹主动脉来验证此人工血管移植后的治疗作用。该研究为小口径人工血管的制备和应用于血管坏死、动脉硬化等诸多疾病提供了基础。

人工血管的移植常用于心脏及周围血管疾病的治疗。小口径血管移植常会因为血栓形成等导致移植失败。合适的机械性能、防止血栓形成以及在血管内表面的快速内皮化是人工血管制备的重要条件。本研究中，我们利用同轴静电纺丝技术制备聚(L-丙交酯)/聚乙烯醇壳芯结构的纳米纤维，并负载可长期缓慢释放的miR-126和肝素以促进血管再生和防止血栓的形成。本研究优化了静电纺丝技术，制备纳米纤维并构建适用于替代血管功能修复的人工血管，通过体外细胞实验及动物体内移植实验，获得了1）具有表面多孔结构的纳米纤维，并通过冷等离子体的表面处理，获得表面孔隙大小可以调节的纳米纤维，从而控制纳米纤维中运载药物的释放速率。2）研究成血管细胞在miR-126的调节下，在小口径人工血管上的快速内皮化。3）通过纳米纤维释放的肝素，来防止在长期的血管植入过程中血栓形成。从而构建可以替代组织血管功能的小口径人工血管。