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Accelerated endothelialization and suppressed thrombus formation of acellular vascular grafts by modifying with neointima-inducing peptide: A time-dependent analysis of graft patency in rat-abdominal transplantation model

Mahara, Atsushi, Sakuma, Takahiro, Mihashi, Naoto, Moritan, Toshiyuki, Yamaoka, Tetsuji
Colloids and surfaces 2019 v.181 pp. 806-813
aorta, endothelial cells, in vitro studies, integrins, ligands, miniature swine, models, peptides, rats, thrombosis
Acellular blood vessels have clinical potential as tissue-engineered vascular grafts. However, neointima is hard to form on their luminal surface. We recently reported the integrin α4β1 ligand peptide (Arg-Glu-Asp-Val) conjugated with a repetitive Pro-Hyp-Gly sequence as luminal surface modifier. By using this peptide, excellent patency of tissue-engineered small-caliber long-bypass grafts in minipig transplantation model was achieved. Here, the time-dependent change of the graft patency is investigated by using rat abdominal transplantation model. In vitro test showed that 86% of the endothelial cells were adhered to the peptide-modified graft surface, while cells were scarcely adhered on the unmodified and random peptide-modified surfaces. After transplantation in the abdominal aorta, the patency of unmodified and random peptide-modified grafts gradually decreased during two to three weeks and reached 20–40% in four weeks. In contrast, 80% of the modified grafts were patent without any thrombus formation at four weeks. These results suggest that the luminal surface modifier was bound to acellular surface through (Pro-Hyp-Gly)7 sequence and improved the in vivo graft patency by endothelialization and thrombus formation suppression.