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Organ-on-a-chip technologies for biomedical research and drug development: A focus on the vasculature.

ABSTRACT: Current biomedical models fail to replicate the complexity of human biology. Consequently, almost 90% of drug candidates fail during clinical trials after decades of research and billions of investments in drug development. Despite their physiological similarities, animal models often misrepresent human responses, and instead, trigger ethical and societal debates regarding their use. The overall aim across regulatory entities worldwide is to replace, reduce, and refine the use of animal experimentation, a concept known as the Three Rs principle. In response, researchers develop experimental alternatives to improve the biological relevance of in vitro models through interdisciplinary approaches. This article highlights the emerging organ-on-a-chip technologies, also known as microphysiological systems, with a focus on models of the vasculature. The cardiovascular system transports all necessary substances, including drugs, throughout the body while in charge of thermal regulation and communication between other organ systems. In addition, we discuss the benefits, limitations, and challenges in the widespread use of new biomedical models. Coupled with patient-derived induced pluripotent stem cells, organ-on-a-chip technologies are the future of drug discovery, development, and personalized medicine.

SUBMITTER: Veliz DS

PROVIDER: S-EPMC7614466 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Organ-on-a-chip technologies for biomedical research and drug development: A focus on the vasculature.

Veliz Diosangeles Soto DS Lin Kai-Lan KL Sahlgren Cecilia C

Smart medicine 20230224 1

Current biomedical models fail to replicate the complexity of human biology. Consequently, almost 90% of drug candidates fail during clinical trials after decades of research and billions of investments in drug development. Despite their physiological similarities, animal models often misrepresent human responses, and instead, trigger ethical and societal debates regarding their use. The overall aim across regulatory entities worldwide is to replace, reduce, and refine the use of animal experime ...[more]

PMID: 37089706

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Project description:The placenta and fetal membrane act as a protective barrier throughout pregnancy while maintaining communication and nutrient exchange between the baby and the mother. Disruption of this barrier leads to various pregnancy complications, including preterm birth, which can have lasting negative consequences. Thus, understanding the role of the feto-maternal interface during pregnancy and parturition is vital to advancing basic and clinical research in the field of obstetrics. However, human subject studies are inherently difficult, and appropriate animal models are lacking. Due to these challenges, in vitro cell culture-based studies are most commonly utilized. However, the structure and functions of conventionally used in vitro 2D and 3D models are vastly different from the in vivo environment, making it difficult to fully understand the various factors affecting pregnancy as well as pathways and mechanisms contributing to term and preterm births. This limitation also makes it difficult to develop new therapeutics. The emergence of in vivo-like in vitro models such as organ-on-chip (OOC) platforms can better recapitulate in vivo functions and responses and has the potential to move this field forward significantly. OOC technology brings together two distinct fields, microfluidic engineering and cell/tissue biology, through which diverse human organ structures and functionalities can be built into a laboratory model that better mimics functions and responses of in vivo tissues and organs. In this review, we first provide an overview of the OOC technology, highlight two major designs commonly used in achieving multi-layer co-cultivation of cells, and introduce recently developed OOC models of the feto-maternal interface. As a vital component of this review, we aim to outline progress on the practicality and effectiveness of feto-maternal interface OOC (FM-OOC) models currently used and the advances they have fostered in obstetrics research. Lastly, we provide a perspective on the future basic research and clinical applications of FM-OOC models, and even those that integrate multiple organ systems into a single OOC system that may recreate intrauterine architecture in its entirety, which will accelerate our understanding of feto-maternal communication, induction of preterm labor, drug or toxicant permeability at this vital interface, and development of new therapeutic strategies.

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Organ-on-a-chip technologies for biomedical research and drug development: A focus on the vasculature.

Publications

Organ-on-a-chip technologies for biomedical research and drug development: A focus on the vasculature.

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