DEVELOPMENT OF AN ORGAN-ON-A-CHIP TO SIMULATE PHYSIOLOGICAL CHARACTERISTICS OF THE HUMAN INTESTINE AGAINST SARS-COV-2

Amanda Maciel Lima; Manoel de Jesus de Aquino Lima; Maria F. C. Amarante; Luís Carlos de Souza Ferreira; Emanuel Carrilho

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Submission

Paper Title

DEVELOPMENT OF AN ORGAN-ON-A-CHIP TO SIMULATE PHYSIOLOGICAL CHARACTERISTICS OF THE HUMAN INTESTINE AGAINST SARS-COV-2

Authors

Amanda Maciel Lima
Manoel de Jesus de Aquino Lima
Maria F. C. Amarante
Luís Carlos de Souza Ferreira
Emanuel Carrilho

Modality

Poster

Subject area

Systems Biology and Modeling

Publishing Date

08/11/2023

Country of Publishing

Brazil | Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeeting2023/638305-development-of-an-organ-on-a-chip-to-simulate-physiological-characteristics-of-the-human-intestine-against-sars-c

ISBN

978-65-272-0061-1

Keywords

Multiplicity Of Infection, Intestine-on-a-chip, SARS-CoV-2

Summary

Organ-on-a-Chip (OoC) platforms are an alternative to help in the pre-clinical stage in drug screening and vaccine models, which will possibly replace conventional experiments of in vivo assays (animals) and in vitro (microplates). intestine, one of the organs most affected by SARS-CoV-2 due to the high expression of ACE2 receptors, the viral replication maybe ma even superior to the replication of do virus in lung tissues. Diarrhea is the most common symptom, and 55% of patients had viral RNA in fecal samples indicating its high viral replication in the intestine. Thus, this work contemplates fabricating low-cost microfluidic device called organ-on-a-chip (OoC), which aims to simulate characteristics at the physiological level of the organ, such as the cell-cell barrier and shear stress caused by fluid flow. The microchips were manufactured using thermoplastic materials (PMMA and PET), double-sided adhesive tape (ARcare and 3M) shaped with a CO2 laser cutter, and assembled layer-by-layer with the custom jig. The biocompatibility and shear stress tests was were performed with Caco-2 and HUVEC cells. At the same time, during the chip development, an assay was performed under 2D conditions to standardize the MOI and infection time of the SARS-CoV-2 (analyses ANOVA). These chip prototypes were submitted to the vascular endothelial cell line (HUVEC) biocompatibility assay, which allowed observing cell development in OoC created with ARcare (OC-ARcare). In OC-ARcare, intestinal epithelial cells (Caco-2) developed under dynamic culture conditions presenting shear stresses of the physiological system of this organ. The shear stress was experienced in the rigorous apical canals in which the HUVEC cells withstood all the shear stresses evaluated (<0.31 dyne cm–2) for three days. However, they showed lower shear stress than capillaries, veins, and arteries (>10 dyne cm–2) of the circulatory system. Caco-2 withstood the shear stress related to the range of the physiological system of the intestine (0.010 dynes cm–2) for six days. Therefore, evaluating the percentage of necrosis and the infection rate, it was verified that the HUVEC cell line was not infected; Calu-3 has a high rate of necrosis and infection; and Caco-2 behaved similarly to VERO, showing a low rate of necrosis and a high rate of infection of the Multiplicity Of Infection (MOI) 0.1 evaluated. Thus, the OC-ARcare (intestine-on-a-chip) model can be considered a promising low-cost alternative to simulate the barrier of cells for viral infection.

Title of the Event: X-Meeting / BSB 2023
City of the Event: Curitiba
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

LIMA, Amanda Maciel et al.. DEVELOPMENT OF AN ORGAN-ON-A-CHIP TO SIMULATE PHYSIOLOGICAL CHARACTERISTICS OF THE HUMAN INTESTINE AGAINST SARS-COV-2.. In: X-Meeting presentations. Anais...Curitiba(PR) Campus da indústria, 2023. Available in: https//www.even3.com.br/anais/xmeeting2023/638305-DEVELOPMENT-OF-AN-ORGAN-ON-A-CHIP-TO-SIMULATE-PHYSIOLOGICAL-CHARACTERISTICS-OF-THE-HUMAN-INTESTINE-AGAINST-SARS-C. Access in: 31/08/2025