Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin.

Buket Baddal,Pasquale Marrazzo

doi:10.3390/pathogens10020203

Buket Baddal, Pasquale Marrazzo

Open Access

https://doi.org/10.3390/pathogens10020203

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Abstract

Bioinspired organ-level in vitro platforms that recapitulate human organ physiology and organ-specific responses have emerged as effective technologies for infectious disease research, drug discovery, and personalized medicine. A major challenge in tissue engineering for infectious diseases has been the reconstruction of the dynamic 3D microenvironment reflecting the architectural and functional complexity of the human body in order to more accurately model the initiation and progression of host–microbe interactions. By bridging the gap between in vitro experimental models and human pathophysiology and providing alternatives for animal models, organ-on-chip microfluidic devices have so far been implemented in multiple research areas, contributing to major advances in the field. Given the emergence of the recent pandemic, plug-and-play organ chips may hold the key for tackling an unmet clinical need in the development of effective therapeutic strategies. In this review, latest studies harnessing organ-on-chip platforms to unravel host–pathogen interactions are presented to highlight the prospects for the microfluidic technology in infectious diseases research.

Highlights

Throughout the timeline of human tissue models, major breakthroughs and convergence from simple two-dimensional (2D) tissue cultures to complex humanoid microfluidic systems have been accomplished in an effort to replicate human physiology, recreate functions of organs, and predict immune and drug responses
This study indicated that the analysis of microbiome contributions to intestinal pathophysiology and the dissection of disease mechanisms in a controlled fashion can be possible on the human gut-on-a-chip [77]
The platform has been increasingly used for studying the initiation and progression of infectious diseases, culture time of organ chips are currently limited to weeks and are not suitable for the study of long-term effects in which a disease may progress for years, such as in chronic hepatitis

Summary

Introduction

Throughout the timeline of human tissue models, major breakthroughs and convergence from simple two-dimensional (2D) tissue cultures to complex humanoid microfluidic systems have been accomplished in an effort to replicate human physiology, recreate functions of organs, and predict immune and drug responses. By administering previously approved drugs in the airway chips under flow at a clinically relevant dose prior to infection, amodiaquine and toremifene were identified as potential entry inhibitors for SARS-CoV-2 [59] Another recent work was reported by Zhang et al who described a biomimetic human disease model of SARS-CoV-2 infection, recapitulating lung injury and immune responses induced by the virus on chip, providing a unique platform that closely mirrored human-relevant responses to SARS-CoV-2 infection [60]. These pioneering studies have unlocked a new step for the use of airway chips to accelerate drug discovery and drug repurposing during viral pandemics. These advances in the field are expected to promote future studies in which biomimetic organ chips will be used as alternatives to preclinical models to study elements of viral pathogenesis and screening of viral therapeutic options [61]

Fungi and Parasites

Microbiome

Moving Forward

Limitations

Conclusions