Reversed-engineered human alveolar lung-on-a-chip model

Abstract

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

Alveolus Lung-on-a-Chip Platform: A Proposal

“…Some PDMS-treatments have been proposed to overcome this problem, as well as alternatives consisting of the use of hydrogels. Huang et al (2021) generated a 3D porous gelatin methacryloyl (GelMa) hydrogel, presenting an alveolar sac-like 3D structure (Figure 2D) [59]. Amongst the advantages of using GelMa instead of synthetic membranes, the stiffness (6.23 ± 0.64 kPa) is within the range reported for native lungs [65].…”

“…Other microfluidic lung systems modeling the alveolar region were set up in other studies, using a similar working principle [59,64]. In some of these models, the flat and synthetic porous membrane was replaced by a biological membrane containing proteins of the ECM and relevant 3D shapes, thus conferring a more physiologically relevant 3D microarchitecture and enhancing their biological performance [59,64].…”

“…Other microfluidic lung systems modeling the alveolar region were set up in other studies, using a similar working principle [59,64]. In some of these models, the flat and synthetic porous membrane was replaced by a biological membrane containing proteins of the ECM and relevant 3D shapes, thus conferring a more physiologically relevant 3D microarchitecture and enhancing their biological performance [59,64]. Although PDMS has been the synthetic material of choice for the fabrication of most lung-on-a-chip devices and their membranes, it presents a high absorption of small molecules such as hydrophobic drugs, thus hindering the widespread use of PDMS-based microfluidic devices for drug screening.…”

A Review of Biomaterials and Scaffold Fabrication for Organ-on-a-Chip (OOAC) Systems

“…Previously groups tended to PDMS as the scaffold of choice when developing Lung-on-a-Chip models [ 9 ]; however, due to its high Young’s modulus, hydrogels are becoming more common as they can mimic the stiffness of the lung ECM. Huang et al recently showed a GelMA based scaffold with a modulus of 6.23 ± 0.64 kPa [ 54 ].…”

Physiological and Disease Models of Respiratory System Based on Organ-on-a-Chip Technology

“…This material has well-defined and interconnected pores that are highly similar to human alveolar sacs. By culturing primary human alveolar epithelial cells on the chip, the functional alveolar epithelium can be easily formed, and breathing movement can be realized [ 48 ].…”