Microfluidic control of oxygen for long-term maintenance of tissues on chip

Abstract

Current in vitro models used for physiological studies and drug development present several drawbacks. They are not able to accurately replicate the in vivo architectures, morphologies, cell diversity and the communications and interactions between the cells and their microenvironments. In this context, micro physiological systems (MPS) technology arises as a new opportunity to overcome these issues. This technology includes organ-on-chip, which in just a few years, they have become a key tool for the modelling of organ functions and the study of disease states and is already presenting promising results and breakthroughs. Another branch of MPS is tissue-on-chip, which instead of culturing cells in a predetermined artificial architecture, the samples are biopsies extracted directly from the body. The culture of tissue explants presents many advantages, for example, they preserve the original three-dimensional architecture, cell types and extracellular matrix of the tissues in vivo. However, this field as not been yet widely explored and still presents many challenges. The aim of this project is the development of new technologies for extending the viability of tissue biopsies in vitro. The main challenges of the long-term culture of tissue explants are the adequate supply of oxygen and nutrients, and the removal of waste. This project seeks to study the oxygen concentration affects the survival ex vivo of tissues to optimise the culture conditions and increase our understanding of the behaviour of the samples outside of the body. A microfluidic platform able to control oxygen concentrations inside culture chambers, with an integrated electronic oxygen sensor to monitor in situ and in real time the gaseous microenvironment has been developed. The system is optimised for the culture of cells in the microfluidic chambers under continuous perfusion and with the ability to subject the samples to specific oxygen tensions. The response of the tissues to hypoxic challenges is measured by looking at the changes in the expression of hypoxia-induced genes.

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Identifiers

ORCID for Fernando Carlos Garcia Garcia: orcid.org/0000-0003-0539-5884

ORCID for Hywel Morgan: orcid.org/0000-0003-4850-5676

ORCID for Emily Swindle: orcid.org/0000-0003-3644-7747

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