Human organotypic bioconstructs from organ-on-chip devices for human-predictive biological insights on drug candidates

ABSTRACT

Introduction: Historically, drug development and marketing failures have been experienced by pharma organizations largely from insufficient human-predictability of biological data.

Areas covered: Organs-on-chips (OOCs) are emerging, cutting edge microphysiology systems for in vitro production of microengineered three-dimensional, miniature organotypic constructs obtained by cultivating small amounts of human primary, or induced pluripotent stem, cells in native-like microhabitats. These preparations circumvent experimental limitations inherent to animal assays and two-dimensional monolayers, the mainstay core biological assays of traditional drug research. This report reviews the fundamental tenets, key components (chip plate, biomaterials, cell differentiation approaches, and monitoring sensors) and issues concerning OOC systems (engineered top-down and bottom-up strategies for tissue/organ assembly, public aids to OOC development, regulatory validation, advantages, limitations, prospective and perspective of OOCs, ethics). Examples of OOC platforms (cancer-, lung-, blood-brain barrier-, heart-, intestine-, kidney-, liver-, pharmacokinetics-, placenta- and vessel-on-chip) and their importance for drug research and development are presented.

Expert opinion: OOC device-generated bioconstructs hold great promise as experimental human tissue and organ platforms for generating human-pertinent knowledge on drug candidates for clinical assessment and reducing reliance on animal models. MPS technologies currently enable ready-to-assemble tissue patches and, hopefully, in coming decades, full-size, patient-personalized organs for regenerative medical interventions.

KEYWORDS:

• Body-on-chips
• drug development
• microfluidics technologies
• organs-on-chips
• drug safety

Article highlights

• Organs-on-chips (OOCs) are novel biological microphysiological systems under development for artificially generating organotypic constructs in three-dimensional formats by cultivation of small amounts of human cells in in vitro native-like microhabitats.

• OOCs circumvent experimental limitations inherent to current animal assays and two-dimensional monolayer cell preparations.

• The article reviews key components and issues concerning OOCs (basic tenets, public aids to OOC development, regulatory validation, advantages, limitations and perspective of OOCs as 21st century human research biomaterial).

• Examples of OOC platforms (heart-, intestine-, kidney-, liver-, pharmacokinetics-, and vessel-on-chip) and their importance to drug research and development are summarized.

• OOC bioconstructs hold great promise as experimental tissue and organ platforms to generate needed clinically pertinent knowledge on drug candidates and progressively phase out the currently heavy reliance on animal models.

• OOC technologies, once perfected, will accelerate the establishment of personalized medicine and, in coming decades, have the potential to produce full-size, patient-personalized organs for regenerative medical interventions.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank N Couvreur for valued suggestions to improve this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.