‘Body-on-a-Chip’ Technology and Supporting Microfluidics

Abstract

In order to effectively streamline current drug development protocols, there is a need to generate high information content preclinical screens capable of generating data with a predictive power in relation to the activity of novel therapeutics in humans. Given the poor predictive power of animal models, and the lack of complexity and interconnectivity of standard in vitro culture methodologies, many investigators are now moving toward the development of physiologically and functionally accurate culture platforms composed of human cells to investigate cellular responses to drug compounds in high-throughput preclinical studies. The generation of complex, multi-organ in vitro platforms, built to recapitulate physiological dimensions, flow rates and shear stresses, is being investigated as the logical extension of this drive. Production and application of a biologically accurate multi-organ platform, or ‘body-on-a-chip’, would facilitate the correct modelling of the dynamic and interconnected state of living systems for high-throughput drug studies as well as basic and applied biomolecular research. This chapter will discuss current technologies aimed at producing ‘body-on-a-chip’ models, as well as highlighting recent advances and important challenges still to be met in the development of biomimetic single-organ systems for drug development purposes.

Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening

“…Although many of these in vitro cardiac assays focus on a single cell type, integration of heart-on-a-chip models with microfluidics (Giridharan, 2014, Giridharan et al, 2010) has opened the possibility of linking multiple in vitro tissue models to create body-on-a-chip devices capable of modeling tissue-tissue cross talk in response to drug treatment or specific pathologies (Esch et al, 2014, Oleaga et al, 2016, Smith et al, 2015, Sung et al, 2013). The importance of cardiac tissue for accurate predictions of system toxicity makes integration of heart-on-a-chip models into such complex systems a vital component for effective modeling of whole-body responses to compound exposure (Sung, Esch, 2013).…”

Case Studies Exemplifying the Transition to Animal Component-free Cell Culture

“…45 This methodology was later extended to various multicellular ‘body-on-a-chip’ models. 46 A human adipose-liver-on-a-chip model that permits the study of factors involved in non-alcoholic fatty liver disease (NAFLD) is a recent example of the use of defined media in microphysiological systems. 47 For the development of this model, patient-derived hepatocytes initially cultured in FBS-containing medium were switched to serum-free conditions on day 3.…”

Barriers to the Uptake of Human-based Test Methods, and how to Overcome Them

“…In vitro technologies are often criticised on the basis of the seemingly impossible task of modelling the functioning of the whole body through a focus on individual parts. While this concern is clearly not without foundation, it ignores two important facts: a) species differences mean that in vivo methods based on non-human biology are inherently unreliable for the purpose of predicting human responses; and b) significant progress has been and is continually being made in the development of more-complex and physiologically more-relevant human-based models, such as human cell systems with high-content output (17)(18)(19), which has been given a significant boost by the explosive development of stem cell technologies (20). While it is unlikely that any single in vitro approach alone will ever fully mirror an intact human, there is good reason to believe that a suitable combination of such tests, alongside low-risk in vivo tests in human volunteers, will ultimately succeed in replacing in vivo testing in non-human species.…”