Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane

Abstract

The air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro. Lung-on-a-chips enable mimicking the breathing movements using a thin, stretchable PDMS membrane. However, they fail to reproduce the characteristic alveoli network as well as the biochemical and physical properties of the alveolar basal membrane. Here, we present a lung-on-a-chip, based on a biological, stretchable and biodegradable membrane made of collagen and elastin, that emulates an array of tiny alveoli with in vivo-like dimensions. This membrane outperforms PDMS in many ways: it does not absorb rhodamine-B, is biodegradable, is created by a simple method, and can easily be tuned to modify its thickness, composition and stiffness. The air-blood barrier is reconstituted using primary lung alveolar epithelial cells from patients and primary lung endothelial cells. Typical alveolar epithelial cell markers are expressed, while the barrier properties are preserved for up to 3 weeks.

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

“…The combination also offers the ability to precisely control the microenvironment created within the chips; the independent chambers enable the creation of unique microenvironments for the various cells. Many groups have taken advantage of the independent nature of their compartmentalized designs to create an ALI [ 18 , 19 , 20 , 21 , 22 , 24 , 25 , 26 , 27 , 28 , 40 , 47 , 49 , 50 , 51 ]. Figure 2 highlights the various ALI architectures that can be generated using microfabrication techniques.…”

“…The stretchable PDMS membranes were integrated with a pneumatic component such that an electro-pneumatic pump would apply a negative pressure, resulting in 0.2 Hz cyclic stretch corresponding to 10% linear strain. More recently, that group replaced the PDMS membrane with a stretchable and biodegradable membrane comprising collagen and elastin, to better reproduce the physical properties of the alveolar basal membrane [ 51 ]. A thin gold mesh was used to support the hydrogel solution and cells could be cultured at an air–liquid interface for several weeks, and a vacuum system was used to apply cyclic strain to the membranes to mimic breathing.…”

Three-Dimensional Cell Cultures as a Research Platform in Lung Diseases and COVID-19

“…Zamprogno et al [ 95 ] proposed a new model or “the second generation” of lung-on-a-chip. In this methodological variant, the porous and stretchable polydimethylsiloxane membrane was replaced by an array of in vivo -like sized alveoli and a stretchable biological membrane.…”

Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

“…Using a similar platform, the same group further examined the influence of mechanical strain on alveolar epithelial wound healing [65]. Furthermore, instead of using conventional PDMS membrane, the same group developed a model of alveolar air-tissue interface on a chip consisting of an array of suspended hexagonal monolayers of nanofibers (made from gelatin or collagen + elastin) supported by microframes [66,67]. The membrane was integrated into a microfluidic device for the patch integration.…”