title: Enhanced in vivo function of bioartificial lungs in rats.
abstract: BACKGROUND
  More than 11 million Americans live with chronic lung disease; in search for an alternative to donor organs, we attempted to regenerate lungs based on perfusion decellularized lung scaffolds that can be transplanted similar to a donor organ.
  
  
  METHODS
  Cadaveric rat lungs were decellularized by detergent perfusion. Resulting scaffolds were mounted in bioreactors and seeded with endothelial and fetal lung cells. Biomimetic organ culture was maintained for 7 days. Resulting bioartificial left lungs were transplanted in orthotopic position after left pneumonectomy in rats. Cadaveric left lung transplants and pneumonectomies served as controls. Blood gas analyses, compliance testing, and fluoroscopies were performed on postoperative days 1, 7, and 14. Lungs were removed for final analysis on day 14.
  
  
  RESULTS
  Perfusion decellularization of cadaveric lungs yielded acellular scaffolds with intact architecture and matrix composition. Alveolar volumes, number, and size were comparable in bioartificial and native lungs, as were gas exchange, vital capacity and compliance in vitro. After using improved graft preservation and postoperative weaning protocols, animals could be fully recovered, and bioartificial lung constructs provided oxygenation as long as 7 days at levels comparable to cadaveric lung transplants. Compliance, gas exchange, and radiographic appearance gradually declined over the subsequent 7 days owing to progressive graft consolidation and inflammation.
  
  
  CONCLUSIONS
  Perfusion decellularization of cadaveric lungs yields intact scaffolds that can be seeded with cells to generate bioartificial lung grafts. After orthotopic transplantation, grafts are perfused by the recipient's circulation, ventilated through the recipient's airway and provide gas exchange in vivo for 7 days.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Song
authors.forename: Sam S
authors.initials: SS
authors.lastname: Kim
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Liu
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Mathisen
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacanti
authors.forename: Harald C
authors.initials: HC
authors.lastname: Ott
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D001784:Blood Gas Analysis; D002908:Chronic Disease; D004195:Disease Models, Animal; D008168:Lung / Q000502:physiology*; D008170:Lung Compliance / Q000502:physiology; D008171:Lung Diseases / Q000503:physiopathology / Q000601:surgery*; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D009926:Organ Preservation / Q000379:methods; D010101:Oxygen Consumption / Q000502:physiology*; D010477:Perfusion / Q000379:methods; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley