title: Blood outgrowth endothelial cells alter remodeling of completely biological engineered grafts implanted into the sheep femoral artery.
abstract: Hemocompatibility of tissue-engineered vascular grafts remains a major hurdle to clinical utility for small-diameter grafts. Here we assessed the feasibility of using autologous blood outgrowth endothelial cells to create an endothelium via lumenal seeding on completely biological, decellularized engineered allografts prior to implantation in the sheep femoral artery. The 4-mm-diameter, 2- to 3-cm-long grafts were fabricated from fibrin gel remodeled into an aligned tissue tube in vitro by ovine dermal fibroblasts prior to decellularization. Decellularized grafts pre-seeded with blood outgrowth endothelial cells (n = 3) retained unprecedented (>95 %) monolayer coverage 1 h post-implantation and had greater endothelial coverage, smaller wall thickness, and more basement membrane after 9-week implantation, including a final week without anti-coagulation therapy, compared with contralateral non-seeded controls. These results support the use of autologous blood outgrowth endothelial cells as a viable source of endothelial cells for creating an endothelium with biological function on decellularized engineered allografts made from fibroblast-remodeled fibrin.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-114 NHH, 312 Church St SE, Minneapolis, MN, 55455, USA.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Meier
authors.forename: Zeeshan H
authors.initials: ZH
authors.lastname: Syedain
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Lahti
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Johnson
authors.forename: Minna H
authors.initials: MH
authors.lastname: Chen
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hebbel
authors.forename: Robert T
authors.initials: RT
authors.lastname: Tranquillo
mesh_terms: D064591:Allografts; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation*; D005240:Feasibility Studies; D005263:Femoral Artery / Q000378:metabolism / Q000601:surgery*; D005337:Fibrin / Q000378:metabolism; D023421:Models, Animal; D011474:Prosthesis Design; D011673:Pulsatile Flow; D012756:Sheep; D013314:Stress, Mechanical; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D005337:Fibrin