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Perfusion‐Decellularization of Porcine Lung and Trachea for Respiratory Bioengineering
Authors:Anton Sabashnikov  Sevil Korkmaz  Shiliang Li  Pal Soos  Roland Ishtok  Nicole Chaimow  Ines Pätzold  Natalie Czerny  Bastian Schmack  Aron‐Frederik Popov  Andre Rüdiger Simon  Matthias Karck  Gabor Szabo
Affiliation:1. Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Middlesex, UK;2. Department of Cardiac Surgery, Heart and Marfan Center, University of Heidelberg, Heidelberg, Germany;3. Heart and Vascular Center, Semmelweis University, Budapest, Hungary;4. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
Abstract:Decellularization of native organs may provide an acellular tissue platform for organ regeneration. However, decellularization involves a trade‐off between removal of immunogenic cellular elements and preservation of biomechanical integrity. We sought to develop a bioartificial scaffold for respiratory tissue engineering by decellularization of porcine lungs and trachea while preserving organ architecture and vasculature. Lung–trachea preparations from 25 German Landrace pigs were perfused in a modified Langendorff circuit and decellularized by an SDC (sodium deoxycholate)‐based perfusion protocol. Decellularization was evaluated by histology and fluorescence microscopy, and residual DNA quantified spectrophotometrically and compared with controls. Airway compliance was evaluated by endotracheal intubation and mechanical ventilation to simulate physiological breathing‐induced stretch. Structural integrity was evaluated by bronchoscopy and biomechanical stress/strain analysis by measuring passive tensile strength, all compared with controls. Decellularized lungs and trachea lacked intracellular components but retained specific collagen fibers and elastin. Quantitative DNA analysis demonstrated a significant reduction of DNA compared with controls (32.8 ± 12.4 μg DNA/mg tissue vs. 179.7 ± 35.8 μg DNA/mg tissue, P < 0.05). Lungs and trachea decellularized by our perfusion protocol demonstrated increased airway compliance but preserved biomechanical integrity as compared with native tissue. Whole porcine lungs–tracheae can be successfully decellularized to create an acellular scaffold that preserves extracellular matrix and retains structral integrity and three‐dimensional architecture to provide a bioartifical platform for respiratory tissue engineering.
Keywords:Decellularization  Tissue engineering  Whole organ concept  Lung  Trachea
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