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Regeneration and orthotopic transplantation of a bioartificial lung

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TLDR
Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange, and regenerated lungs into orthotopic position showed in vivo function.
Abstract
About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with endstage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cellseeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient’s circulation and ventilated by means of the recipient’s airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.

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An overview of tissue and whole organ decellularization processes.

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The acute respiratory distress syndrome.

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Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

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Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds

TL;DR: In this paper, the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations.

Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional

TL;DR: The fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffolds, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach are described.
References
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Journal ArticleDOI

Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart

TL;DR: Eight constructs decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent a cellular valves and intact chamber geometry that could generate pump function in a modified working heart preparation.
Journal ArticleDOI

Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer

TL;DR: Although bronchiolar cells and alveolar cells are proposed to be the precursor cells of adenocarcinoma, this work points to bronchioalveolar stem cells as the putative cells of origin for this subtype of lung cancer.
Journal ArticleDOI

Clinical transplantation of a tissue-engineered airway

TL;DR: The results show that a cellular, tissue-engineered airway with mechanical properties that allow normal functioning, and which is free from the risks of rejection, is produced, suggesting that autologous cells combined with appropriate biomaterials might provide successful treatment for patients with serious clinical disorders.
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