Long-term patency remains the main challenge for small-diameter vascular grafts in clinical applications. In addition to anticoagulation and endothelialization, antiproliferative treatment of the autologous vessels at the suture site and mechanical compatibility are also important influences on long-term patency rates. In order to address these issues simultaneously, this study constructed a functionally segmented small-diameter vascular graft with anticoagulant and endothelialization functions in the whole-graft and antiproliferation functions at both ends by emulsion electrospinning. The functionally segmented vascular grafts were composed of thermoplastic polyurethane (TPU) and Type I collagen (Col), with heparin (Hep)/anti-CD133 antibody in the whole segment and rapamycin (RAPA) loaded at both ends. In addition，through component modulation, we prepared blood vessels possessing excellent mechanical matching with human autologous blood vessels, which is highly conducive to enhance the stability of blood vessels and promote endothelialization growth. Moreover, compared with the TPU group, the thermoplastic polyurethane/collagen/heparin/anti-CD133 antibody/rapamycin (TCHCR) group showed better biocompatibility and hemocompatibility. In vivo implantation experiments in the New Zealand Great White Rabbit have shown that the TCHCR group exhibited good anticoagulant, endothelialization and antiproliferative effects. Therefore，the functionally segmented vascular grafts we prepared may succeed in solving the problem of vascular long-term patency rates.
Capture of endothelial progenitor cells (EPCs) in situ has been considered as a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and implant devices. In this study, a CD133 + EPC capture surface was fabricated by grafting CD133 antibody (a more specific EPC surface marker than CD34) and Arg-Glu-Asp-Val (REDV) peptideon the methacrylate-grafted hyaluronic acid (MA-HA) and heparin-hybridized (MA-HA&Heparin) resisting layer. Vascular endothelial growth factor (VEGF) was further conjugated to the immobilized heparin. This engineered surface showed good hemocompatibility and significantly higher ability of capturing CD133 + EPCs from human peripheral blood mononuclear cells (PBMCs) and obviously upregulated the expression of endothelial cell (EC) marker genes of EPCs such as VEGF receptor 2 (VEGFR2), CD31 , VE-cadherin, and von Willebrand factor (vWF), facilitating the differentiation of EPCs into ECs. The dramatically enhanced EPC proliferation on this surface was dependent on the integrin-VEGFR synergistic signaling, as ERK1/2 phosphorylation was only significantly enhanced on the REDV and VEGF co-immobilized surface. This study highlights a new surface coating strategy for blood-contact materials based on the specific EPC capturing and rapid endothelialization. Statement of Significance Capture of endothelial progenitor cells (EPCs) in situ is a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and scaffolds. More specific capture of EPCs by targeting CD133 rather than CD34 can better reduce the risk of inflammation and restenosis. On the other hand, an appropriate microenvironment for EPC proliferation is equally important for endothelialization, which is rarely considered by the existing EPC capture strategies. In this study, the capture ratio of EPCs was significantly increased by simultaneously grafting CD133 antibody and VEGF on a MA-HA and heparin-hybridized antifouling layer. Further, proliferation of EPCs after capture was significantly promoted by grafting VEGF and REDV peptide through the integrin–VEGFR synergistic signaling. This study highlights a new strategy for the surface coating of blood-contact materials based on specific EPC capture and rapid endothelialization.
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