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

TLDR

The air‑blood barrier’s complex architecture and dynamic environment are difficult to replicate in vitro, and existing lung‑on‑chip devices using stretchable PDMS membranes fail to reproduce the alveolar network or the biochemical and physical properties of the alveolar basal membrane. This study aims to develop a lung‑on‑chip that employs a biological, stretchable, biodegradable collagen‑elastin membrane to emulate an array of tiny alveoli with in vivo‑like dimensions. The device recreates the alveolar network and breathing dynamics by integrating the collagen‑elastin membrane with primary lung alveolar epithelial and endothelial cells. The collagen‑elastin membrane outperforms PDMS by not absorbing rhodamine‑B, being biodegradable, easy to fabricate, and tunable in thickness, composition, and stiffness, while supporting cell marker expression and preserving barrier properties for up to three weeks.

Abstract

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.