Lung bioengineering: advances and challenges in lung decellularization and recellularization

Abstract

Purpose of review Bioengineering the lung based on its natural extracellular matrix (ECM) offers novel opportunities to overcome the shortage of donors, to reduce chronic allograft rejections, and to improve the median survival rate of transplanted patients. During the last decade, lung tissue engineering has advanced rapidly to combine scaffolds, cells, and biologically active molecules into functional tissues to restore or improve the lung's main function, gas exchange. This review will inspect the current progress in lung bioengineering using decellularized and recellularized lung scaffolds and highlight future challenges in the field. Recent findings Lung decellularization and recellularization protocols have provided researchers with tools to progress toward functional lung tissue engineering. However, there is continuous evolution and refinement particularly for optimization of lung recellularization. These further the possibility of developing a transplantable bioartificial lung. Summary Bioengineering the lung using recellularized scaffolds could offer a curative option for patients with end-stage organ failure but its accomplishment remains unclear in the short-term. However, the state-of-the-art of techniques described in this review will increase our knowledge of the lung ECM and of chemical and mechanical cues which drive cell repopulation to improve the advances in lung regeneration and lung tissue engineering.

Implications for Extracellular Matrix Interactions With Human Lung Basal Stem Cells in Lung Development, Disease, and Airway Modeling

“…The complexity and importance of the native ECM in the regulation of BCs is highlighted as we have yet to create an in vitro culture model that is capable of the long-term expansion of BCs while maintaining their phenotypic stability (Zabner et al, 2003;Cortiella et al, 2010;Liu et al, 2012;Mou et al, 2016;Gentzsch et al, 2017;Peters-Hall et al, 2018;Greaney et al, 2020;Carraro et al, 2020b). To circumnavigate the difficulties of culturing airway cells on an artificial matrix, some have turned to decellularization and recellularization of the lung or trachea (Cortiella et al, 2010;Ott et al, 2010;Price et al, 2010;Badylak et al, 2011b;Au -Bonvillain et al, 2013;Keane et al, 2015;Uriarte et al, 2018;Greaney et al, 2020). Decellularization methods attempt to remove all cellular material, leaving behind the intact ECM (Ott et al, 2010;Price et al, 2010;Badylak et al, 2011b;Uriarte et al, 2018).…”

“…To circumnavigate the difficulties of culturing airway cells on an artificial matrix, some have turned to decellularization and recellularization of the lung or trachea (Cortiella et al, 2010;Ott et al, 2010;Price et al, 2010;Badylak et al, 2011b;Au -Bonvillain et al, 2013;Keane et al, 2015;Uriarte et al, 2018;Greaney et al, 2020). Decellularization methods attempt to remove all cellular material, leaving behind the intact ECM (Ott et al, 2010;Price et al, 2010;Badylak et al, 2011b;Uriarte et al, 2018). With present techniques, some DNA and other cytoplasmic and/or nuclear material is usually retained by the scaffold, but the composition and mechanical properties of the ECM are largely preserved (Badylak et al, 2011b;Uriarte et al, 2018).…”

“…Decellularization methods attempt to remove all cellular material, leaving behind the intact ECM (Ott et al, 2010;Price et al, 2010;Badylak et al, 2011b;Uriarte et al, 2018). With present techniques, some DNA and other cytoplasmic and/or nuclear material is usually retained by the scaffold, but the composition and mechanical properties of the ECM are largely preserved (Badylak et al, 2011b;Uriarte et al, 2018). Several laboratories have attempted to repopulate the ECM with ex vivo expanded cells (Cortiella et al, 2010;Au -Bonvillain et al, 2013;Gilpin et al, 2014;Keane et al, 2015;Burgstaller et al, 2018;Gilpin and Wagner, 2018;Uriarte et al, 2018;Greaney et al, 2020;Ravindra et al, 2021).…”

“…With present techniques, some DNA and other cytoplasmic and/or nuclear material is usually retained by the scaffold, but the composition and mechanical properties of the ECM are largely preserved (Badylak et al, 2011b;Uriarte et al, 2018). Several laboratories have attempted to repopulate the ECM with ex vivo expanded cells (Cortiella et al, 2010;Au -Bonvillain et al, 2013;Gilpin et al, 2014;Keane et al, 2015;Burgstaller et al, 2018;Gilpin and Wagner, 2018;Uriarte et al, 2018;Greaney et al, 2020;Ravindra et al, 2021). While this has yielded promising results, there are many aspects, particularly in the recellularization process, that must be refined before decellularization/recellularization can be widely used in clinical applications.…”

A Fully Automated High-Throughput Bioreactor System for Lung Regeneration

“…We have yet to define the ideal combination of regenerative cell types, and we continue to work toward defining specific ex vivo biomimetic culture conditions that adequately mature and prepare the lung constructs for transplantation. 2,7 In the present report, we describe a novel, high-throughput, and automated multichannel bioreactor system, which supports the simultaneous recellularization and culture of up to five rat lungs in parallel under controlled conditions. Our system allows for the regulation of variable biomimetic conditions, including perfusion flow rates and pressure targets, as well as multiple modes of fluid and air ventilation during lung culture.…”