4.6 Article

Rapid in situ endothelialization of a small diameter vascular graft with catalytic nitric oxide generation and promoted endothelial cell adhesion

期刊

JOURNAL OF MATERIALS CHEMISTRY B
卷 3, 期 47, 页码 9212-9222

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ROYAL SOC CHEMISTRY
DOI: 10.1039/c5tb02080h

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资金

  1. National Key Basic Research Program of China (973'' Program) [2012CB725204]
  2. National Natural Science Foundation of China [51073081]
  3. PCSIRT [IRT13023]
  4. Tianjin Natural Science Foundation [13JCYBJC24900, 13JCZDJC27800]

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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.

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