Abstract：
Rapid endothelialization is extremely essential for the success of small-diameter tissue-engineered vascular graft (TEVG) (<6 mm) transplantation. However, severe inflammation in situ often causes cellular energy decline of endothelial cells. The cellular energy supply involved in vascular graft therapy remains unclear, and whether promoting energy supply would be helpful in the regeneration of vascular grafts needs to be established. In our work, we generated an AMPK activator (5-aminoimidazole-4-carboxamide ribonucleotide, AICAR) immobilized vascular graft. AICAR-modified vascular grafts were successfully generated by the co-electrospinning technique. In vitro results indicated that AICAR could upregulate energy supply in endothelial cells and reprogram macrophages (MΦ) to assume an anti-inflammatory phenotype. Furthermore, endothelial cells (ECs) co-cultured with AICAR achieved higher survival rates, better migration, and angiogenic capacity than the controls. Concurrently, a rabbit carotid artery transplantation model was used to investigate AICAR-modified vascular grafts at different time points. The results showed that AICAR-modified vascular grafts had higher patency rates (92.9% and 85.7% at 6 and 12 weeks, respectively) than those of the untreated group (11.1% and 0%). In conclusion, AICAR strengthened the cellular energy state and attenuated the adverse effects of inflammation. AICAR-modified vascular grafts achieved better vascular remodeling. This study provides a new perspective on promoting the regeneration of small-diameter vascular grafts.
摘要：
快速内皮化对于小直径组织工程血管移植物（TEVG）（<6mm）移植的成功至关重要。然而,严重的原位炎症常导致内皮细胞的细胞能量下降。血管移植治疗中涉及的细胞能量供应仍不清楚，需要确定促进能量供应是否有助于血管移植物的再生。在我们的工作中,我们产生了AMPK激活剂（5-氨基咪唑-4-甲酰胺核糖核苷酸，AICAR)固定化血管移植物。通过共静电纺丝技术成功地产生了AICAR修饰的血管移植物。体外结果表明，AICAR可以上调内皮细胞的能量供应，并重新编程巨噬细胞（MΦ）以呈现抗炎表型。此外，与AICAR共培养的内皮细胞（ECs）获得了更高的存活率，更好的迁移，和血管生成能力比对照组。同时,采用兔颈动脉移植模型研究不同时间点的AICAR修饰血管移植.结果表明，AICAR修饰的血管移植物的通畅率较高（在6周和12周时分别为92.9％和85.7％，分别）高于未处理组（11.1%和0%）。总之,AICAR增强了细胞能量状态并减轻了炎症的不利影响。AICAR修饰的血管移植物实现了更好的血管重塑。本研究为促进小直径血管移植物的再生提供了新的视角。
