title: Contrasting biofunctionalization strategies for the enhanced endothelialization of biodegradable vascular grafts.
abstract: Surface modification of biodegradable vascular grafts is an important strategy to improve the in situ endothelialization of tissue engineered vascular grafts (TEVGs) and prevent major complications associated with current synthetic grafts. Important strategies for improving endothelialization include increasing endothelial cell mobilization and increased endothelial cell capture through biofunctionalization of TEVGs. The objective of this study was to assess two biofunctionalization strategies for improving endothelialization of biodegradable polyester vascular grafts. These techniques consisted of cross-linking heparin to graft surfaces to immobilize vascular endothelial growth factor (VEGF) or antibodies against CD34 (anti-CD34Ab). To this end, heparin, VEGF, and anti-CD34Ab attachment and quantification assays confirmed the efficacy of the modification strategy. Cell attachment and proliferation on these groups were compared to unmodified grafts in vitro and in vivo. To assess in vivo graft functionality, the grafts were implanted as inferior vena cava interpositional conduits in mice. Modified vascular grafts displayed increased endothelial cell attachment and activity in vivo, according to microscopy techniques, histological results, and eNOS expression. Inner lumen diameter of the modified grafts was also better maintained than controls. Overall, while both functionalized grafts outperformed the unmodified control, grafts modified with anti-CD34Ab appeared to yield the most improved results compared to VEGF-loaded grafts.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: A J
authors.initials: AJ
authors.lastname: Melchiorri
authors.forename: N
authors.initials: N
authors.lastname: Hibino
authors.forename: T
authors.initials: T
authors.lastname: Yi
authors.forename: Y U
authors.initials: YU
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Sugiura
authors.forename: S
authors.initials: S
authors.lastname: Tara
authors.forename: T
authors.initials: T
authors.lastname: Shinoka
authors.forename: C
authors.initials: C
authors.lastname: Breuer
authors.forename: J P
authors.initials: JP
authors.lastname: Fisher
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001807:Blood Vessel Prosthesis / Q000639:trends; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D058017:Vascular Grafting / Q000379:methods* / Q000639:trends
chemical_list: D018952:Antigens, CD34; D020099:Coated Materials, Biocompatible; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006493:Heparin