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      Implantation of VEGF-functionalized cell-free vascular grafts: regenerative and immunological response

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          Abstract

          Recently, our group demonstrated that immobilized VEGF can capture flowing endothelial cells (ECs) from the blood in vitro and promote endothelialization and patency of acellular tissue–engineered vessels (A-TEVs) into the arterial system of an ovine animal model. Here, we demonstrate implantability of submillimeter diameter heparin and VEGF-decorated A-TEVs in a mouse model and discuss the cellular and immunologic response. At 1 mo postimplantation, the graft lumen was fully endothelialized, as shown by expression of EC markers such as CD144, eNOS, CD31, and VEGFR2. Interestingly, the same cells coexpressed leukocyte/macrophage (Mϕ) markers CD14, CD16, VEGFR1, CD38, and EGR2. Notably, there was a stark difference in the cellular makeup between grafts containing VEGF and those containing heparin alone. In VEGF-containing grafts, infiltrating monocytes (MCs) converted into anti-inflammatory M2-Mϕs, and the grafts developed well-demarcated luminal and medial layers resembling those of native arteries. In contrast, in grafts containing only heparin, MCs converted primarily into M1-Mϕs, and the endothelial and smooth muscle layers were not well defined. Our results indicate that VEGF may play an important role in regulating A-TEV patency and regeneration, possibly by regulating the inflammatory response to the implants.—Smith, R. J., Jr., Yi, T., Nasiri, B., Breuer, C. K., Andreadis, S. T. Implantation of VEGF-functionalized cell-free vascular grafts: regenerative and immunological response.

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          Author and article information

          Journal
          FASEB J
          FASEB J
          fasebj
          fasebj
          The FASEB Journal
          Federation of American Societies for Experimental Biology (Bethesda, MD, USA )
          0892-6638
          1530-6860
          April 2019
          10 January 2019
          1 April 2020
          : 33
          : 4
          : 5089-5100
          Affiliations
          [* ]Department of Biomedical Engineering, University at Buffalo, State University of New York, Amherst, New York, USA;
          []Nationwide Children’s Hospital, Columbus, Ohio, USA;
          []Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA; and
          [§ ]Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Amherst, New York, USA
          Author notes
          [1 ]Correspondence: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York at Buffalo, 908 Furnas Hall, North Campus, Amherst, NY 14260-4200, USA. E-mail: sandread@ 123456buffalo.edu
          Article
          PMC6436645 PMC6436645 6436645 FJ_201801856R
          10.1096/fj.201801856R
          6436645
          30629890
          03de2840-8a5b-4119-8aaf-12c010ce2151
          © FASEB
          History
          : 05 September 2018
          : 13 December 2018
          Page count
          Figures: 7, Tables: 0, Equations: 0, References: 82, Pages: 12
          Categories
          Research
          Custom metadata
          v1

          immunoengineering,monocytes,endothelialization,inflammation

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