title: Successful tissue engineering of competent allogeneic venous valves.
abstract: OBJECTIVE
  The purpose of this study was to evaluate whether tissue-engineered human allogeneic vein valves have a normal closure time (competency) and tolerate reflux pressure in vitro.
  
  
  METHODS
  Fifteen human allogeneic femoral vein segments containing valves were harvested from cadavers. Valve closure time and resistance to reflux pressure (100 mm Hg) were assessed in an in vitro model to verify competency of the vein valves. The segments were tissue engineered using the technology of decellularization (DC) and recellularization (RC). The decellularized and recellularized vein segments were characterized biochemically, immunohistochemically, and biomechanically.
  
  
  RESULTS
  Four of 15 veins with valves were found to be incompetent immediately after harvest. In total, 2 of 4 segments with incompetent valves and 10 of 11 segments with competent valves were further decellularized using detergents and DNAse. DC resulted in significant decrease in host DNA compared with controls. DC scaffolds, however, retained major extracellular matrix proteins and mechanical integrity. RC resulted in successful repopulation of the lumen and valves of the scaffold with endothelial and smooth muscle cells. Valve mechanical parameters were similar to the native tissue even after DC. Eight of 10 veins with competent valves remained competent even after DC and RC, whereas the two incompetent valves remained incompetent even after DC and RC. The valve closure time to reflux pressure of the tissue-engineered veins was <0.5 second.
  
  
  CONCLUSIONS
  Tissue-engineered veins with valves provide a valid template for future preclinical studies and eventual clinical applications. This technique may enable replacement of diseased incompetent or damaged deep veins to treat axial reflux and thus reduce ambulatory venous hypertension.
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Department of Surgery, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Kuna
authors.affiliation: Department of Vascular Surgery, Oslo Vascular Centre, Oslo University Hospital, Aker, Norway.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosales
authors.affiliation: Department of Vascular Surgery, Oslo Vascular Centre, Oslo University Hospital, Aker, Norway.
authors.forename: Jonny
authors.initials: J
authors.lastname: Hisdal
authors.affiliation: Department of Vascular Surgery, Oslo Vascular Centre, Oslo University Hospital, Aker, Norway.
authors.forename: Eivind K
authors.initials: EK
authors.lastname: Osnes
authors.affiliation: Department of Vascular Surgery, Oslo Vascular Centre, Oslo University Hospital, Aker, Norway.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Sundhagen
authors.affiliation: Department of Chemistry, Materials, and Surfaces, SP Technical Research Institute of Sweden, Borås, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Bäckdahl
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Department of Surgery, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: suchitra.holgersson@surgery.gu.se.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Sumitran-Holgersson
authors.affiliation: Department of Vascular Surgery, Oslo Vascular Centre, Oslo University Hospital, Aker, Norway; Vascular Department, University of Oslo, Oslo, Norway.
authors.forename: Jørgen J
authors.initials: JJ
authors.lastname: Jørgensen
mesh_terms: D005268:Femoral Vein; D006801:Humans; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014689:Venous Insufficiency / Q000628:therapy*; D014690:Venous Pressure; D055422:Venous Valves