3D Bioelectronic Gut Model for Modelling Pathogenic Enteric Virus Infections in vitro

Reece McCoy^a, Jack Hankinson^b, Valeria Lulla^b, Roisin Owens^a

^aDepartment of Chemical Engineering and Biotechnology, University of Cambridge, CB3 0AS, UK

^bDepartment of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge UK

Proceedings of Bioelectronic Interfaces: Materials, Devices and Applications (CyBioEl)

Limassol, Cyprus, 2024 October 22nd - 25th

Organizers: Eleni Stavrinidou and Achilleas Savva

Contributed talk, Reece McCoy, presentation 056
DOI: https://doi.org/10.29363/nanoge.cybioel.2024.056
Publication date: 28th June 2024

Human enteric viruses, a diverse array of pathogens recognized for their significant role in global diarrheal disease, pose a considerable public health threat. Their environmental resilience, extensive viral shedding, and transmission via the fecal-oral route underscore the urgency of investigation^[1].

To understand intricate dynamics of viral interactions, elucidate entry mechanisms, and identify anti-viral interventions that impede host entry, the development of in vitro models which faithfully replicate complexities of the gut becomes imperative^[2].

We have engineered a 3D model of the intestine, intricately hosted on a conducting PEDOT:PSS scaffold^[3,4]. This model not only emulates the intestinal epithelial lining more closely than conventional 2D models, but also captures the importance of the lamina propria layer, the connective tissue beneath, which contains important connective proteins and facilitated cellular crosstalk with the overlying epithelium. Monitoring the barrier's integrity over time is achieved through electrochemical impedance spectroscopy (EIS), offering a highly time resolved understanding of the model's response to enteric viruses, including poliovirus-like CVA13.

Our findings reveal the capabilities of our 3D bioelectronic gut models – including sensing virus-induced barrier disruption. We are further aiming to demonstrate electrical monitoring of virus-induced cellular extrusion of epithelial cells demonstrating a novel pathway for viral shedding and disease progression along the intestinal tract^[5]. This approach holds promise in investigating the contraction of diseases and interrupting transmission pathways, which would be a significant stride towards enhanced public health outcomes.

[1] T.-T. Fong, E. K. Lipp, Microbiology and Molecular Biology Reviews 2005, 69, 357.

[2] R. McCoy, S. Oldroyd, W. Yang, K. Wang, D. Hoven, D. Bulmer, M. Zilbauer, R. M. Owens, Advanced Science 2023, 2306727.

[3] C. M. Moysidou, D. C. van Niekerk, V. Stoeger, C. Pitsalidis, L. A. Draper, A. M. Withers, K. Hughes, R. McCoy, R. Acharya, C. Hill, R. M. Owens, Small Science 2024.

[4] C. Pitsalidis, D. van Niekerk, C.-M. Moysidou, A. J. Boys, A. Withers, R. Vallet, R. M. Owens, Sci Adv 2022, 8, 4761.

[5] J. Moshiri, A. R. Craven, S. B. Mixon, M. R. Amieva, K. Kirkegaard, Nat Microbiol 2023, 8, 629.

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