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

Michela Licciardello; Cecilia Traldi; Martina Cicolini; Valentina Bertana; Simone Luigi Marasso; Matteo Cocuzza; Chiara Tonda-Turo; Gianluca Ciardelli

doi:10.3389/fbioe.2024.1346660

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

Front Bioeng Biotechnol. 2024 Apr 5:12:1346660. doi: 10.3389/fbioe.2024.1346660. eCollection 2024.

Authors

Michela Licciardello^{1

2

3}, Cecilia Traldi^{1

2

3}, Martina Cicolini^{2

4}, Valentina Bertana⁴, Simone Luigi Marasso^{4

5}, Matteo Cocuzza⁴, Chiara Tonda-Turo^#^{1

2

3}, Gianluca Ciardelli^#^{1

2

3

6}

Affiliations

¹ La.Di.Spe Bioengineerig, Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Turin, Italy.
² PolitoBIOMed Lab, Politecnico di Torino, Turin, Italy.
³ Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Italy.
⁴ ChiLab- Materials and Microsystems Laboratory, Politecnico di Torino, Department of Applied Science and Technology (DISAT), Chivasso, Italy.
⁵ CNR-IMEM, National Research Council-Institute of Materials for Electronics and Magnetism, Parma, Italy.
⁶ CNR-IPCF, National Research Council-Institute for Chemical and Physical Processes, Pisa, Italy.

^# Contributed equally.

Abstract

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 in vitro 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 in vivo 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.

Keywords: ECM-like substrate; alveolar-capillary barrier; alveolus-on-a-chip; cell tri-culture; in vitro models.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work has received funding from the Regione Piemonte under the Digital tEchnology For Lung Cancer Treatment (DEFLECT) project.