Abstract
Organs-on-chips (OoCs), also known as microphysiological systems or 'tissue chips' (the terms are synonymous), have attracted substantial interest in recent years owing to their potential to be informative at multiple stages of the drug discovery and development process. These innovative devices could provide insights into normal human organ function and disease pathophysiology, as well as more accurately predict the safety and efficacy of investigational drugs in humans. Therefore, they are likely to become useful additions to traditional preclinical cell culture methods and in vivo animal studies in the near term, and in some cases replacements for them in the longer term. In the past decade, the OoC field has seen dramatic advances in the sophistication of biology and engineering, in the demonstration of physiological relevance and in the range of applications. These advances have also revealed new challenges and opportunities, and expertise from multiple biomedical and engineering fields will be needed to fully realize the promise of OoCs for fundamental and translational applications. This Review provides a snapshot of this fast-evolving technology, discusses current applications and caveats for their implementation, and offers suggestions for directions in the next decade.
Highlights
Drug development is slow and costly, driven mainly by high attrition rates in clinical trials[1]
Remarkable increases in our understanding of the molecular underpinnings of human diseases and our ability to model in vivo cell, tissue and organ-level biology have been made over the past three decades, the number of US Food and Drug Administration (FDA)-approved drugs per billion US$ spent on research and development has decreased monotonically since 19502
Drug development needs new approaches, paradigms and tools to reverse these trends and deliver on the promise of science for patients2. 35 animal models have contributed enormously both to our understanding of physiology and disease, and to the development of new medicines, researchers have long been aware of the frequent discordance between animal and human studies and the need for modeling and testing platforms that would be more predictive of human responses[3,4]
Summary
1. Time and dose-dependent LDH release, apoptosis, plus decreased albumin and Vernetti et al 201661 endothelial cells are layered 2. Trovafloxacin + LPS and urea secretion in glass and PDMS levofloxacin + LPS (immune- 2. Increased LDH release and apoptosis with microfluidic chip.
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