Citation: Mohgan, R.; Candasamy, M.; Mayuren, J.; Singh, S.K.; Gupta, G.; Dua, K.; Chellappan, D.K. Emerging Paradigms in Bioengineering the Lungs. Bioengineering 2022, 9, 195. https:// doi.org/10.3390/bioengineering 9050195 Academic Editor: Christian Demitri Received: 3 April 2022 Accepted: 26 April 2022 Published: 1 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). bioengineering Review Emerging Paradigms in Bioengineering the Lungs Raxshanaa Mohgan 1 , Mayuren Candasamy 2 , Jayashree Mayuren 3 , Sachin Kumar Singh 4,5 , Gaurav Gupta 6,7,8 , Kamal Dua 5,9 and Dinesh Kumar Chellappan 2, * 1 School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia; raxshanaa.mohgan@student.imu.edu.my 2 Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia; mayurencandasamy@imu.edu.my 3 Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia; jayashree@imu.edu.my 4 School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara 144411, India; sachin.16030@lpu.co.in 5 Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Sydney 2007, Australia; kamal.dua@uts.edu.au 6 School of Pharmacy, Suresh Gyan Vihar University, Jagatpura 302017, India; drgaurav.gupta@mygyanvihar.com 7 Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India 8 Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, India 9 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney 2007, Australia * Correspondence: dinesh_kumar@imu.edu.my Abstract: In end-stage lung diseases, the shortage of donor lungs for transplantation and long waiting lists are the main culprits in the significantly increasing number of patient deaths. New strategies to curb this issue are being developed with the help of recent advancements in bioengineering technology, with the generation of lung scaffolds as a steppingstone. There are various types of lung scaffolds, namely, acellular scaffolds that are developed via decellularization and recellularization techniques, artificial scaffolds that are synthesized using synthetic, biodegradable, and low immuno- genic materials, and hybrid scaffolds which combine the advantageous properties of materials in the development of a desirable lung scaffold. There have also been advances in the design of bioreactors in terms of providing an optimal regenerative environment for the maturation of functional lung tissue over time. In this review, the emerging paradigms in the field of lung tissue bioengineering will be discussed. Keywords: lung bioengineering; scaffolds; lung-on-a-chip; lung transplantation; artificial lung; bioprinting 1. Introduction Each year, more than 4600 lung transplantations are carried out globally, of which 55% are performed in North America and 36% in Europe [1]. The replacement of diseased lungs with a pair of healthy ones in lung transplantation (LTx) increases both the life expectancy and quality of life in patients [2,3]. However, this approach is only preferred when patients are not responding to medications. The most common indications where transplantation is opted for are in the end stage of diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), interstitial pulmonary fibrosis, and primary pulmonary arterial hypertension [3,4]. In terms of pulmonary malignancy, it was found that a select group of patients undergoing Ltx had desirable outcomes [5]. In patients with severe unresolving COVID-19 associated with acute respiratory distress syndrome, lung transplantation was the only option [6]. The assessment process for LTx is usually long and complicated. The American Tho- racic Society and International Society for Heart and Lung Transplantation have developed Bioengineering 2022, 9, 195. https://doi.org/10.3390/bioengineering9050195 https://www.mdpi.com/journal/bioengineering