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De novo lung biofabrication: clinical need, construction methods, and design strategy

Published:April 29, 2019DOI:https://doi.org/10.1016/j.trsl.2019.04.008
      Chronic lung disease is the 4th leading cause of death in the United States. Due to a shortage of donor lungs, alternative approaches to support failing, native lungs have been attempted, including mechanical ventilation and various forms of artificial lungs. However, each of these support methods causes significant complications when used for longer than a few days and are thus not capable of long-term support. For artificial lungs, complications arise due to interactions between the artificial materials of the device and the blood of the recipient. A potential new approach is the fabrication of lungs from biological materials, such that the gas exchange membranes provide a more biomimetic blood-contacting interface. Recent advancements with three-dimensional, soft-tissue biofabrication methods and the engineering of thin, basement membranes demonstrate the potential of fabricating a lung scaffold from extracellular matrix materials. This scaffold could then be seeded with endothelial and epithelial cells, matured within a bioreactor, and transplanted. In theory, this fully biological lung could provide improved, long-term biocompatibility relative to artificial lungs, but significant work is needed to perfect the organ design and construction methods. Like artificial lungs, biofabricated lungs do not need to follow the shape and structure of a native lung, allowing for simpler manufacture. However, various functional requirements must still be met, including stable, efficient gas exchange for a period of years. Design decisions depend on the disease state, how the organ is implanted, and the latest biofabrication methods available in a rapidly evolving field.

      Abbreviations:

      ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 13), ADAMTS18 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 18), AT I (alveolar type I), AT2 (alveolar type II), AV (arteriovenous), AVCO2R (arteriovenous CO2 removal), COPD (chronic obstructive pulmonary disease), CF (cystic fibrosis), ECCO2R (extracorporeal CO2 removal), EBM (engineered basement membrane), ECM (extracellular matrix), ECMO (extracorporeal membrane oxygenation), fIIa (factor IIa), fXa (factor Xa), fIXa (factor IXa), fXIa (factor XIa), fXIIa (factor XIIa), fV (factor V), fVIII (factor VIII), fVIIa (factor VIIa), FRESH (Freeform Reversible Embedding of Suspended Hydrogels), hiPSCs (human-induced pluripotent stem cells), HLA (human leukocyte antigen), ILD (interstitial lung disease), LSM (lateral supportive membranes), MV (mechanical ventilation), NIV (noninvasive ventilation), PA-LA (pulmonary artery to left atrium), VA (venoarterial), VV (venovenous), 2D (2-dimensional), 3D (3-dimensional)
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