通过仿生天然细胞外基质构建功能型人工血管促进组织再生重构

Because of the high rate of restenosis in small-diameter vascular grafts, there are no commercial products that have been successfully utilized in clinic. The main reason could be explained by the poor hameocompatibility and cell affinity, which often lead to the acute thrombosis in early stage, limited tissue regeneration and remodeling, as well as the calcification in vascular wall in late stage. In this project, functional vascular grafts with bi-layer structure will be designed and fabricated by mimicking the native ECM (structure and function). Inner layer provides an optimal interface to inhibit coagulation and accelerate endothelialization, while outer layer was prepared by LBL technique based on collagen Ⅳ and hyaluronan in order to induce the migration and differentiation of vascular stem/progenitor cells, and thus enhancing the regeneration and remodeling of vascular smooth muscle. Finally, the repair and regeneration of diseased vascular tissue will be realized, and long-term vascular homeostasis will be anticipated.

小口径人工血管因再狭窄发生率高，目前仍没有产品成功应用于临床。其主要原因是惰性的合成材料血液相容性和细胞亲和性差，植入初期易引发血栓，不利于组织再生重构，晚期还会发生血管壁钙化。本项目拟通过模拟天然血管细胞外基质结构和功能，仿生构建复合结构的功能型人工血管。血管内层为具有抗凝血和促内皮形成的功能表面，外层通过层层组装LBL技术构建四型胶原和透明质酸的微环境，以诱导血管干/祖细胞的迁移并调控其向血管细胞的定向分化，促进平滑肌组织再生重构，最终完成血管组织的修复重建并实现血管长期稳态。

小口径人工血管因再狭窄发生率高，目前仍没有产品成功应用于临床。其主要原因是惰性的合成材料血液相容性和细胞亲和性差，初期易引发血栓，长期植入后组织再生非常有限。本项目提出通过诱导内源性血管干/祖细胞实现组织再生的思路，成功制备了具有微纳米复合纤维结构的人工血管，其作为载体通过向体内递送重要血管活性物质（细胞因子Dkk3，HDAC-7活性多肽、外泌体等），有效诱导血管干/祖细胞的迁移和定向分化并对血管祖细胞迁移的相关机制进行了深入研究。