title: Pressure- and flow-controlled media perfusion differently modify vascular mechanics in lung decellularization.
abstract: Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. Perfusion of decellularizing media through the pulmonary artery has shown to be effective. How vascular perfusion pressure and flow vary throughout lung decellularization, which is not well known, is important for optimizing the process (minimizing time) while ensuring scaffold integrity (no barotrauma). This work was aimed at characterizing the pressure/flow relationship at the pulmonary vasculature and at how effective vascular resistance depends on pressure- and flow-controlled variables when applying different methods of media perfusion for lung decellularization. Lungs from 43 healthy mice (C57BL/6; 7-8 weeks old) were investigated. After excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization with a solution of 1% sodium dodecyl sulfate (SDS). Pressure (PPA) and flow (V'PA) at the pulmonary artery were continuously measured. Decellularization media was perfused through the pulmonary artery: (a) at constant PPA=20 cmH2O or (b) at constant V'PA=0.5 and 0.2 ml/min. Effective vascular resistance was computed as Rv=PPA/V'PA. Rv (in cmH2O/(ml/min)); mean±SE) considerably varied throughout lung decellularization, particularly for pressure-controlled perfusion (from 29.1±3.0 in baseline to a maximum of 664.1±164.3 (p<0.05), as compared with flow-controlled perfusion (from 49.9±3.3 and 79.5±5.1 in baseline to a maximum of 114.4±13.9 and 211.7±70.5 (p<0.05, both), for V'PA of 0.5 and 0.2 ml/min respectively. Most of the media infused to the pulmonary artery throughout decellularization circulated to the airways compartment across the alveolar-capillary membrane. This study shows that monitoring perfusion mechanics throughout decellularization provides information relevant for optimizing the process time while ensuring that vascular pressure is kept within a safety range to preserve the organ scaffold integrity.
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; Master's and Doctoral Degree Programs in Rehabilitation Sciences, Nove de Julho University, Sao Paulo, Brazil.
authors.forename: Renata K
authors.initials: RK
authors.lastname: da Palma
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; Institut de Bioenginyeria de Catalunya, Barcelona, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Campillo
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; CIBER Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Uriarte
authors.affiliation: Master's and Doctoral Degree Programs in Rehabilitation Sciences, Nove de Julho University, Sao Paulo, Brazil.
authors.forename: Luis V F
authors.initials: LV
authors.lastname: Oliveira
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; Institut de Bioenginyeria de Catalunya, Barcelona, Spain; CIBER Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Navajas
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; CIBER Enfermedades Respiratorias, Madrid, Spain; Institut Investigacions Biomediques August Pi Sunyer, Barcelona, Spain. Electronic address: rfarre@ub.edu.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
mesh_terms: D000818:Animals; D057005:Bioengineering / Q000379:methods*; D001696:Biomechanical Phenomena; D008168:Lung / Q000098:blood supply* / Q000166:cytology*; D008297:Male; D055595:Mechanical Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion; D011312:Pressure; D011651:Pulmonary Artery / Q000502:physiology*; D014655:Vascular Resistance
keywords: Acellular lung; Fluid mechanics; Lung bioengineering; Lung scaffold; Organ biofabrication; Tissue engineering; Vascular resistance