Bioengineering and Clinical Translation of Human Lung and its Components

Abstract

Clinical lung transplantation has rapidly established itself as the gold standard of treatment for end‐stage lung diseases in a restricted group of patients since the first successful lung transplant occurred. Although significant progress has been made in lung transplantation, there are still numerous obstacles on the path to clinical success. The development of bioartificial lung grafts using patient‐derived cells may serve as an alternative treatment modality; however, challenges include developing appropriate scaffold materials, advanced culture strategies for lung‐specific multiple cell populations, and fully matured constructs to ensure increased transplant lifetime following implantation. This review highlights the development of tissue‐engineered tracheal and lung equivalents over the past two decades, key problems in lung transplantation in a clinical environment, the advancements made in scaffolds, bioprinting technologies, bioreactors, organoids, and organ‐on‐a‐chip technologies. The review aims to fill the lacuna in existing literature toward a holistic bioartificial lung tissue, including trachea, capillaries, airways, bifurcating bronchioles, lung disease models, and their clinical translation. Herein, the efforts are on bridging the application of lung tissue engineering methods in a clinical environment as it is thought that tissue engineering holds enormous promise for overcoming the challenges associated with the clinical translation of bioengineered human lung and its components.

High-Throughput Bioprinting of the Nasal Epithelium using Patient-derived Nasal Epithelial Cells

“…Therefore, in-vitro culture of functional respiratory epithelium is crucial in current respiratory tissue engineering approaches to overcome these limitations [14]. Recently, respiratory epithelial invitro systems have become an alternative to expensive, labor-intensive animal studies, which also raise ethical issues, regardless of their relevance to human physiology [15,16]. These in-vitro systems utilize a wide range of cell sources and cultivation protocols allowing the investigation of respiratory diseases and the effects of various environmental factors on the airways [17,18].…”

A 3D Printed Ventilated Perfused Lung Model Platform to Dissect the Lung’s Response to Viral Infection in the Presence of Respiration

“…Over the years, researchers have made significant progress in developing increasingly simple to complex lung tissue models that reproduce specific components of human lung responses (3)(4)(5)(6) . However, all these models have limitations, particularly to capture complex cell-cell and cell-matrix interactions and to replicate the intricate 3D anatomy of the lung parenchyma (7,8). Creating a sophisticated 3D in-vitro lung model presents several challenges due to the complex anatomy of the lung matrix and parenchyma, which include the requirement for connections between alveolar units and airways surrounded by endothelium (9)(10)(11)(12).…”

High-throughput bioprinting of the nasal epithelium using patient-derived nasal epithelial cells

“…Therefore, in-vitro culture of functional respiratory epithelium is crucial in current respiratory tissue engineering approaches to overcome these limitations [ 14 ]. Recently, respiratory epithelial in-vitro systems have become an alternative to expensive, labor-intensive animal studies, which also raise ethical issues, regardless of their relevance to human physiology [ 15 , 16 ]. These in-vitro systems utilize a wide range of cell sources and cultivation protocols allowing the investigation of respiratory diseases and the effects of various environmental factors on the airways [ 17 , 18 ].…”