title: Controlled gas exchange in whole lung bioreactors.
abstract: In cellular, tissue-level or whole organ bioreactors, the level of dissolved oxygen is one of the most important factors requiring control. Hypoxic environments may lead to cellular apoptosis, while hyperoxic environments may lead to cellular damage or dedifferentiation, both resulting in loss of overall tissue function. This manuscript describes the creation, characterization and validation of a bioreactor system that can control oxygen delivery based on real-time metabolic demand of cultured whole lung tissue. A mathematical model describing and predicting gas exchange within the tunable bioreactor system is developed. In addition, the inherent gas exchange properties of the bioreactor and the inherent oxygen consumption rates of native rat lungs are determined, thereby providing a quantitative relationship between system parameters and levels of dissolved oxygen. Finally, the mathematical model is validated during whole lung culture under a range of system parameters. The system presented here provides a quantitative relationship between the concentration of dissolved oxygen, tissue oxygen consumption rates, and controllable system parameters that introduce gasses into the bioreactor. This relationship not only enables the maintenance of constant levels of dissolved oxygen throughout a culture period during which cells are replicating, but also provides noninvasive and real-time estimation of the metabolic and proliferative states of native or engineered lung tissue simply through dissolved oxygen measurements. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biomedical Engineering, Yale University School of Engineering and Applied Science, New Haven, CT, USA.
authors.forename: Alexander J
authors.identifier: 0000-0001-8691-2614
authors.initials: AJ
authors.lastname: Engler
authors.affiliation: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Andrew V
authors.identifier: 0000-0002-9301-0616
authors.initials: AV
authors.lastname: Le
authors.affiliation: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Baevova
authors.affiliation: Department of Biomedical Engineering, Yale University School of Engineering and Applied Science, New Haven, CT, USA.|Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
mesh_terms: D000818:Animals; D019149:Bioreactors; D002452:Cell Count; D004247:DNA / Q000378:metabolism; D004867:Equipment Design; D005740:Gases / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000502:physiology*; D008954:Models, Biological; D010101:Oxygen Consumption; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D005740:Gases; D004247:DNA
keywords: bioreactor; gas exchange; lung; mathematical model; oxygen