A paper-based in vitro model for on-chip investigation of the human respiratory system

Abstract

A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. Culturing cells at air-liquid interface (ALI) is essential for creating functional in-vitro models of lung tissue. We present the use of direct-patterned laser-treated hydrophobic paper as an effective semi-permeable membrane, ideal for ALI cell culture. The surface properties of the paper is modified through selective CO2 laserassisted treatment to create a unique porous substrate with hydrophilic regions that regulates fluid diffusion and cell attachment. To select the appropriate model, four promising hydrophobic films were compared with each other in terms of gas permeability and long-term strength in aqueous environment (wetstrength). Among the investigated substrates, parchment paper showed the fastest rate of oxygen permeability (3 times more than conventional transwell cell culture membranes), with the least variation in its dry and wet tensile strength (124 MPa and 58 MPa, remaining unchanged after 7 days of submersion in PBS). The final paper based platform provides an ideal, robust, and inexpensive device for generating monolayers of lung epithelial cells on-chip in a high-throughput fashion for disease modelling and in-vitro drug testing.

Biomedical Application of Functional Materials in Organ-on-a-Chip

“…The Khademhosseini group presented the use of hydrophobic paper as a semi-permeable membrane for culturing cells at the air-liquid interface. The final paper-based device provides a cost-effective platform for human respiratory system studies under physiologically relevant conditions ( Figure 1C) (Rahimi et al, 2016).…”

Modelling upper respiratory tract diseases: getting grips on host-microbe interactions in chronic rhinosinusitis using in vitro technologies

“…Another limitation to current models is failure of the host compartment to adequately mimic the host microenvironment as most often undifferentiated host cell monolayers or differentiated epithelial cell cultures are used, without taking into account tissue-specific mechanical or chemical stimuli. Organ-on-chip models offer a way to take these stimuli into account mimicking the spatial structures and mechanical stimuli observed in host tissue in microfluidic devices [ 107 , 115 , 116 ]. The ALI culture method, also applied in these devices, provides conditions for co-culture resembling the in vivo situation, where bacteria are exposed to atmospheric conditions and are obliged to acquire nutrients and growth factors through the epithelial cell layer.…”

Disrupting Experimental Strategies for Inhalation Toxicology: The Emergence of Microengineered Breathing-Smoking Human Lung-on-a-Chip

“…Table 1 summarizes key aspects of this platform and its comparison against airway microphysiological models developed by other groups. [30][31][32][33] In a follow-up study, the same research team elegantly reverses engineered design principles of an average smoker's lung to create a ''Breathing-Smoking Human Lung-on-a-Chip'' in vitro (Fig. 1).…”