How to build a lung: latest advances and emerging themes in lung bioengineering

Abstract

Chronic respiratory diseases remain a major cause of morbidity and mortality worldwide. The only option at end-stage disease is lung transplantation, but there are not enough donor lungs to meet clinical demand. Alternative options to increase tissue availability for lung transplantation are urgently required to close the gap on this unmet clinical need. A growing number of tissue engineering approaches are exploring the potential to generate lung tissue for transplantation. Both biologically derived and manufactured scaffolds seeded with cells and grown have been explored in pre-clinical studies, with the eventual goal of generating functional pulmonary tissue for transplantation. Recently, there have been significant efforts to scale-up cell culture methods to generate adequate cell numbers for human-scale bioengineering approaches. Concomitantly, there have been exciting efforts in designing bioreactors that allow for appropriate cell seeding and development of functional lung tissue over time. This review aims to present the current state-of-the-art progress for each of these areas and to discuss promising new ideas within the field of lung bioengineering.

Evolution of Bioengineered Lung Models: Recent Advances and Challenges in Tissue Mimicry for Studying the Role of Mechanical Forces in Cell Biology

“…Furthermore, it has been shown that decellularized extracellular matrix (dECM) containing essential proteins for cell attachment and proliferation, could be a good candidate to improve the biocompatibility of copolymers . In a recent study, hybrid electrospun scaffold of poly‐L‐lactic acid and dECM (derived from pig lung) for in vitro ASM model showed that dECM improved physical characteristics (e.g., wettability) …”

“…The hydrophilicity, biocompatibility, and mechanical properties (Young's modulus: 1.77 ± 0.09 MPa) of these hybrid materials make them promising membrane materials for lung models, although they have not been widely applied in lung research, yet. dECM‐derived native lung tissue, a biomimetic mixture of natural ECM proteins, is another promising natural material because of its excellent biocompatibility features, although it does not have sufficiently biomimetic mechanical properties . As this deficiency can be compensated by hybridization with a synthetic polymer, several synthetic/dECM copolymers have been recently manufactured for tissue engineering application …”

Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases 2017. An Official American Thoracic Society Workshop Report

“…The ECM is one of the major constituents in whole-organ decellularized scaffolds that are being explored for ex vivo engineering of lung tissue. Although a number of key hurdles have been overcome (e.g., protocols to decellularize human and large animal scaffolds, expansion of cells for re-endothelialization and re-epithelialization of whole human and large animal constructs) ( 29 ), a number of challenges remain. Recent work by Dr. Harald Ott’s group in a short-term porcine model of transplantation has identified a number of key hurdles, including achievement of higher-level cellular function such as surfactant expression.…”

Lung regeneration: implications of the diseased niche and ageing

“…A promising area of research is the (re)generation of pulmonary tissue using ex vivo bioengineering methods. In these approaches, cells are combined with a scaffold outside of the body, with the goal of forming new tissue for transplantation [106]. Scaffolds can be derived from either biological or artificial materials (or a combination thereof in hybrid approaches) and could be seeded with an appropriate cell source to regenerate functional lung tissue for subsequent transplantation.…”