A miniaturized multicellular platform to mimic the 3D structure of the alveolar-capillary barrier

• Published in: Frontiers in bioengineering and biotechnology Vol. 12; p. 1346660
• Main Authors: Licciardello, Michela, Traldi, Cecilia, Cicolini, Martina, Bertana, Valentina, Marasso, Simone Luigi, Cocuzza, Matteo, Tonda-Turo, Chiara, Ciardelli, Gianluca
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2024
• Subjects: alveolar-capillary barrier; alveolus-on-a-chip; cell tri-culture; ECM-like substrate; in vitro models; ECM-like substrate; cell tri-culture; alveolar-capillary barrier; in vitro models; alveolus-on-a-chip
• ISSN: 2296-4185; 2296-4185
• DOI: 10.3389/fbioe.2024.1346660

Several diseases affect the alveoli, and the efficacy of medical treatments and pharmaceutical therapies is hampered by the lack of pre-clinical models able to recreate the diseases. Microfluidic devices, mimicking the key structural and compositional features of the alveoli, offer several advantages to medium and high-throughput analysis of new candidate therapies. Here, we developed an alveolus-on-a-chip recapitulating the microanatomy of the physiological tissue by including the epithelium, the fibrous interstitial layer and the capillary endothelium. A PDMS device was obtained assembling a top layer and a bottom layer obtained by replica molding. A polycaprolactone/gelatin (PCL-Gel) electrospun membrane was included within the two layers supporting the seeding of 3 cell phenotypes. Epithelial cells were grown on a fibroblast-laden collagen hydrogel located on the top side of the PCL-Gel mats while endothelial cells were seeded on the basolateral side of the membrane. The innovative design of the microfluidic device allows to replicate both cell-cell and cell-extracellular matrix interactions according to the cell arrangement along with the establishment of physiologically relevant air-liquid interface conditions. Indeed, high cell viability was confirmed for up to 10 days and the formation of a tight endothelial and epithelial barrier was assessed by immunofluorescence assays.