Wang Yuanyuan, Chen Siyuan, Pan Yiwa, Gao Jingchen, Tang Di, Kong Deling, Wang Shufang
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.
J Mater Chem B. 2015 Dec 21;3(47):9212-9222. doi: 10.1039/c5tb02080h. Epub 2015 Nov 16.
Thrombosis and neointimal hyperplasia are the main causes for the failure of small diameter vascular grafts, and a complete and functional endothelium is essential in preventing these problems. Therefore, grafts that could be endothelialized rapidly are highly desirable. This study constructed a vascular graft with catalytic nitric oxide (NO) generation and promoted endothelial cell (EC) adhesion for rapid in situ endothelialization, and examined the in vivo performance of an NO-generating vascular graft for the first time. A macroporous electrospun polycaprolactone (PCL) graft was prepared and modified via layer-by-layer self-assembly. Organoselenium immobilized polyethyleneimine was loaded onto the graft for in situ catalytic NO generation, while hyaluronic acid was grafted with an EC specific peptide Arg-Glu-Asp-Val and deposited to promote EC adhesion. This dual-modified material generated a strong and sustained flow of NO from S-nitrosoglutathione and significantly enhanced EC adhesion in vitro. In a co-culture experiment of ECs and smooth muscle cells (SMCs), this material promoted the adhesion of ECs and increased the EC/SMC ratio. After implantation in rats, the modified grafts showed a remarkably promoted endothelialization compared to PCL ones with an endothelium coverage of 89% versus 55% after 4 weeks, and the ECs on modified grafts were better organized in a pattern similar to that of the native vessel. The results indicated that the combination of catalytic NO generation and promoted EC adhesion proposed in this work may be a promising method for rapid endothelialization of small diameter vascular grafts.
血栓形成和新生内膜增生是小口径血管移植物失效的主要原因，而完整且具有功能的内皮对于预防这些问题至关重要。因此，能够快速实现内皮化的移植物备受期待。本研究构建了一种具有催化一氧化氮（NO）生成功能并促进内皮细胞（EC）黏附以实现快速原位内皮化的血管移植物，并首次检测了产生NO的血管移植物的体内性能。制备了一种大孔静电纺聚己内酯（PCL）移植物，并通过层层自组装进行改性。将固定有机硒的聚乙烯亚胺负载到移植物上以实现原位催化NO生成，同时将接枝了EC特异性肽Arg-Glu-Asp-Val的透明质酸沉积到移植物上以促进EC黏附。这种双重改性材料可从S-亚硝基谷胱甘肽产生强大且持续的NO流，并在体外显著增强EC黏附。在EC和平滑肌细胞（SMC）的共培养实验中，这种材料促进了EC的黏附并提高了EC/SMC比例。植入大鼠体内后，与PCL移植物相比，改性移植物的内皮化明显得到促进，4周后内皮覆盖率分别为89%和55%，并且改性移植物上的EC排列更有序，类似于天然血管。结果表明，本研究中提出的催化NO生成与促进EC黏附相结合的方法可能是一种实现小口径血管移植物快速内皮化的有前景的方法。
