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3D culture models to study SARS-CoV-2 infectivity and antiviral candidates: From spheroids to bioprinting
Bruna A G de Melo1, Julia C Benincasa1, Elisa M Cruz1
1Department of Biochemistry, Paulista School of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.
Abstract:
The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is receiving worldwide attention, due to the severity of the disease (COVID-19) that resulted in more than a million global deaths so far. The urgent need for vaccines and antiviral drugs is mobilizing the scientific community to develop strategies for studying the mechanisms of SARS-CoV-2 infection, replication kinetics, pathogenesis, host-virus interaction, and infection inhibition. In this work, we review the strategies of tissue engineering in the fabrication of three-dimensional (3D) models used in virology studies, which presented many advantages over conventional cell cultures, such as complex cytoarchitecture and a more physiological microenvironment. Scaffold-free (spheroids and organoids) and scaffold-based (3D scaffolding and 3D bioprinting) approach allow the biofabrication of more realistic models relevant to the pandemic, to be used as in vitro platforms for the development of new vaccines and therapies against COVID-19.
Insights
Tissue engineering creates advanced 3D models for studying SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) and COVID-19. These models offer a more realistic in vitro platform for developing vaccines and antiviral therapies.
Area of Science:
- Virology
- Tissue Engineering
- Biotechnology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, has led to over a million deaths globally.
- There is an urgent need for effective vaccines and antiviral drugs to combat the virus.
- Conventional cell cultures have limitations in mimicking the complexity of human physiology during viral infections.
Purpose of the Study:
- To review tissue engineering strategies for fabricating 3D models for virology research.
- To highlight the advantages of 3D models over traditional cell cultures for studying viral infections.
- To discuss the application of these models in developing COVID-19 vaccines and therapies.
Main Methods:
- Review of scaffold-free methods (spheroids, organoids).
- Review of scaffold-based methods (3D scaffolding, 3D bioprinting).
- Fabrication of advanced 3D in vitro models.
Main Results:
- 3D models offer complex cytoarchitecture and a more physiological microenvironment compared to 2D cultures.
- Scaffold-free and scaffold-based approaches enable the creation of realistic models.
- These models are suitable for studying viral infection mechanisms, replication, pathogenesis, and host-virus interactions.
Conclusions:
- Tissue engineering provides powerful tools for developing advanced 3D models for virology.
- These 3D models represent a significant advancement for in vitro research on SARS-CoV-2 and COVID-19.
- Biofabricated 3D models are crucial for accelerating the development of novel vaccines and antiviral treatments.

