肝素/M2巨噬细胞外泌体复合水凝胶促进小口径人工血管原位再生与重建

小口径人工血管（SDAVG）的原位再生与重建是机体和材料共同参与的复杂过程。本项目围绕“如何实现小口径人工血管体内原位再生与重建”这一科学问题，提出：制备一种新型的双层小口径人工血管，其内层为周向取向的微孔道结构，外层为微纳米纤维结构。制备并表征M2巨噬细胞外泌体（M2-exo）和肝素水凝胶。将包裹M2-exo的肝素水凝胶负载于微孔道内实现外泌体的缓慢释放。通过大鼠腹主动脉体内移植实验，研究微孔道结构对于细胞募集与诱导血管再生的影响，研究肝素募集细胞生长因子对血管再生的影响，研究M2-exo对于炎症反应的调控、M1巨噬细胞向M2巨噬细胞的极化转型及对血管再生的影响，研究人工血管长期体内植入的内膜增生及钙化。优化制备出能够再生类似于天然血管结构的人工血管。本研究为SDVG的设计和制备，实现小口径血管的原位再生具有重要的理论意义和实用价值。

The in situ regeneration and reconstruction of small diameter vascular graft(SDAVG) are complex process involving in the body and biomaterials，The SDAVG structure and inflammatory response play crucial role. This project focus on the scientific issue of ”How to achieve in situ regeneration and reconstruction of small diameter blood vessels?”. Putting forward: the preparation of a new type SDAVG with double layers, whose the inner layer is a microchannel structure with circumferential orientation, and the outer layer is made up of micro/nano fibers. The exosome of M2 macrophage (M2-exo) and heparin hydrogels will be prepared and characterized. The heparin hydrogel with M2-exo will be loaded inside of the microchannels to maintain sustained release of M2-exo. The effect of microchannel structure on cell recruitment and regeneration of SDAVG are evaluated by implantation in rat abdominal aorta, Investigating the recruitment of cell growth factor by heparin hydrogel and effect on its regeneration of blood vessels. Investigating the regulation role of M2-exo on inflammatory response, the phenotypic switch of M1 to M2 macrophage and its effect on regeneration of blood vessels. The intimal hyperplasia and calcification of SDAVG will be studied through long-term implantation. Optimized structure of SDAVG which is able to regenerate native vascular structures will be fabricated. This study is of great theoretical and practical significance for the design and preparation of SDAVG, and the in-situ regeneration of SDAVG.