Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Abstract

Over the past years, advanced in vitro pulmonary platforms have witnessed exciting developments that are pushing beyond traditional preclinical cell culture methods. Here, we discuss ongoing efforts in bridging the gap between in vivo and in vitro interfaces and identify some of the bioengineering challenges that lie ahead in delivering new generations of human-relevant in vitro pulmonary platforms. Notably, in vitro strategies using foremost lung-on-chips and biocompatible "soft" membranes have focused on platforms that emphasize phenotypical endpoints recapitulating key physiological and cellular functions. We review some of the most recent in vitro studies underlining seminal therapeutic screens and translational applications and open our discussion to promising avenues of pulmonary therapeutic exploration focusing on liposomes. Undeniably, there still remains a recognized trade-off between the physiological and biological complexity of these novel in vitro lung models and their ability to deliver assays with throughput capabilities. The upcoming years are thus anticipated to see further developments in broadening the applicability of such in vitro systems and accelerating therapeutic exploration for drug discovery and translational medicine in treating respiratory disorders.

An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics

“…Finally, although we have only modeled positive pleural pressure by raising the height of the syringe, negative pleural pressure can be similarly modeled by lowering the syringe height below the device height and dynamic pleural pressure changes by using an automated system that adjusts the height of the syringe in concert with the air pressure. Apart from providing insights into the role of biomechanics on lung function, these platforms can also potentially serve as important predictive tools to prevent lung injuries or for drug screening (Artzy-Schnirman et al, 2021).…”

Investigation of the role of the autophagic protein LC3B in the regulation of human airway epithelium cell differentiation in COPD using a biomimetic model

“…Notably, compared with traditional cell culture and differentiation methods [ [45] , [46] , [47] ], by adjusting the collagen coating, cell density, culture medium composition, and the time point of transition from submerged to ALI culture, small airway differentiation can be effectively induced without additional cell mechanical stress [ [48] , [49] , [50] ] and maintain a physiological microenvironment similar to that in the human body and recapitulate functionally differentiated cell types, including basal, secretory, mucous, and ciliated cells. The length and beating of cilia also yielded data similar to those in the human body ( Supplementary Table S3 ), verifying that the biomimetic model of small airways can provide a better representation of physiological data.…”

Editorial: Innovative In Vitro Models for Pulmonary Physiology and Drug Delivery in Health and Disease

“…One critical issue lies in the existing discrepancy between the performance of therapeutic candidates in preclinical in vivo animal models and their high failure rate for safety and/or efficacy in reaching clinical trials. More generally, the efforts advocating for improved human-relevant in vitro lung models are intimately tied to current discussions on alternatives to in vivo animal experiments (Bonniaud et al, 2018) and have been further underlined with major hurdles faced with animal experiments regarding the extent to which these shed light on human pulmonary physiology and diseases (van der Worp et al, 2010;Benam et al, 2015;Artzy-Schnirman et al, 2021).…”