Rapid endothelialization of small diameter vascular grafts by a bioactive integrin-binding ligand specifically targeting endothelial progenitor cells and endothelial cells.
Rapid endothelialization of small diameter vascular grafts by a bioactive integrin-binding ligand specifically targeting endothelial progenitor cells and endothelial cells.
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DOI：
10.1016/j.actbio.2020.03.005
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发表时间：
2020-05
影响因子：
9.7
通讯作者：
Wang A
中科院分区：
文献类型：
--
作者：
Hao D;Fan Y;Xiao W;Liu R;Pivetti C;Walimbe T;Guo F;Zhang X;Farmer DL;Wang F;Panitch A;Lam KS;Wang A
Establishing and maintaining a healthy endothelium on vascular and intravascular devices is crucial for the prevention of thrombosis and stenosis. Generating a biofunctional surface on vascular devices to recruit endothelial progenitor cells (EPCs) and endothelial cells (ECs) has proven efficient in promoting in situ endothelialization. However, molecules conventionally used for EPC/EC capturing generally lack structural stability, capturing specificity, and biological functionalities, which have limited their applications. Discovery of effective, specific, and structurally stable EPC/EC capturing ligands is desperately needed. Using the high-throughput One-Bead One-Compound combinatorial library screening technology, we recently identified a disulfide cyclic octa-peptide LXW7 (cGRGDdvc), which possesses strong binding affinity and functionality to EPCs/ECs, weak binding to platelets, and no binding to inflammatory cells. Because LXW7 is cyclic and 4 out of the 8 amino acids are unnatural D-amino acids, LXW7 is highly proteolytically stable. In this study, we applied LXW7 to modify small diameter vascular grafts using a Click chemistry approach. In vitro studies demonstrated that LXW7-modified grafts significantly improved EPC attachment, proliferation and endothelial differentiation and suppressed platelet attachment. In a rat carotid artery bypass model, LXW7 modification of the small diameter vascular grafts significantly promoted EPC/EC recruitment and rapidly achieved endothelialization. At 6 weeks after implantation, LXW7-modified grafts retained a high patency of 83%, while the untreated grafts had a low patency of 17%. Our results demonstrate that LXW7 is a potent EPC/EC capturing and platelet suppressing ligand and LXW7-modified vascular grafts rapidly generate a healthy and stable endothelial interface between the graft surface and the circulation to reduce thrombosis and improve patency.
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DOI：
10.1016/j.jconrel.2012.05.034
发表时间：
2012-08-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
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通讯作者：
Li S
影响因子：
4.8
作者：
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通讯作者：
Niklason, Laura E.
DOI：
10.1073/pnas.0704581104
发表时间：
2007-07-17
影响因子：
11.1
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2004.06.055
发表时间：
2004-08-06
影响因子：
3.1
作者：
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通讯作者：
Davies, PF
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影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.