The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies

Abstract

High-quality, in vitro screening tools are essential in identifying promising compounds during drug development. Tests with currently used cell-based assays provide an indication of a compound's potential therapeutic benefits to the target tissue, but not to the whole body. Data obtained with animal models often cannot be extrapolated to humans. Multicompartment microfluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models, may contribute to improving the drug development process. These scaled-down devices, termed micro cell culture analogs (μCCAs) or body-on-a-chip devices, can simulate multitissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response. The devices also provide a means for relatively high-throughput screening of drug combinations and, when utilized with a patient's tissue sample, an opportunity for individualized medicine. Here we review efforts made toward the development of microfabricated cell culture systems and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multiorgan metabolic interactions. In addition to their use in drug development, the devices also can be used to estimate the toxicity of chemicals as occupational hazards and environmental contaminants.

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

“…To this end, the recently emerged organ-on-a-chip systems that combine advanced microfluidic technologies and tissue engineering approaches to simulate both the biology and physiology of human organs have been developed (8,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). These miniaturized human organ models have several advantages over conventional models, such as more accurate prediction of human responses and, in particular, multiorgan interactions when different organ modules are assembled in a single fluid circuit (7,31).…”

Tissue engineered organoids for neural network modelling

“…Further models of heart, cartilage and skin, as well as functional systems such as the vascular, endocrine, musculoskeletal, and nervous systems have been reviewed by Benam et al 9 Body-and human-on-a-chip systems further aim to draw connectivity between each of these separate models in order to mimic basic physiological function on a larger scale. 10,11 Tissue models must present a reasonable mimic of normal physiological function in order that they are deemed useful; it is this 'use' which is now expanding as we gradually increase our micro/ nanofabrication capabilities to guide complex tissue engineering approaches, better replicating normal and diseased function. Our models allow for better understanding of function and dysfunction, disease spread and how efforts for treatment may be optimised.…”

Towards engineering integrated cardiac organoids: beating recorded

“…Originating from the concept of tissue engineering (2), yet with a distinct aim that is to construct models of human tissues and organs outside the body for improved biological, pharmaceutical, and environmental studies (3)(4)(5)(6) rather than repairing them in vivo, these microphysiological systems have further undergone significant developments with the inclusion of the microfabrication and microfluidics technologies that conveniently bring in the beneficial complexity (4,7). While various microfabrication strategies allow us to engineer microscale tissue and organ units that possess shapes and architecture that mimic their in vivo counterparts (8)(9)(10), the ability to manipulate fluids at small scales leads to reproduction of the dynamic microenvironments indispensable for the functions of natural tissues and organs (1,4), both of which are otherwise not achievable using the conventional planar, static culture platforms.…”

“…While various microfabrication strategies allow us to engineer microscale tissue and organ units that possess shapes and architecture that mimic their in vivo counterparts (8)(9)(10), the ability to manipulate fluids at small scales leads to reproduction of the dynamic microenvironments indispensable for the functions of natural tissues and organs (1,4), both of which are otherwise not achievable using the conventional planar, static culture platforms. Of note, these individual microphysiological systems can be further linked together in such a way that the interconnected multi-unit platforms recapitulate the linkage of the various tissues and organs in their native arrangements, facilitating investigations of the intricate interactions among these different components in vitro (3)(4)(5)(6).…”