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The organ-on-a-chip (OoC) paves a way for biomedical applications ranging from preclinical to clinical translational precision. The current trends in the in vitro modeling is to reduce the complexity of human organ anatomy to the fundamental cellular microanatomy as an alternative of recreating the entire cell milieu that allows systematic analysis of medicinal absorption of compounds, metabolism, and mechanistic investigation. The OoC devices accurately represent human physiology in vitro; however, it is vital to choose the correct chip materials. The potential chip materials include inorganic, elastomeric, thermoplastic, natural, and hybrid materials. Despite the fact that polydimethylsiloxane is the most commonly utilized polymer for OoC and microphysiological systems, substitute materials have been continuously developed for its advanced applications. The evaluation of human physiological status can help to demonstrate using noninvasive OoC materials in real-time procedures. Therefore, this Review examines the materials used for fabricating OoC devices, the application-oriented pros and cons, possessions for device fabrication and biocompatibility, as well as their potential for downstream biochemical surface alteration and commercialization. The convergence of emerging approaches, such as advanced materials, artificial intelligence, machine learning, three-dimensional (3D) bioprinting, and genomics, have the potential to perform OoC technology at next generation. Thus, OoC technologies provide easy and precise methodologies in cost-effective clinical monitoring and treatment using standardized protocols, at even personalized levels. Because of the inherent utilization of the integrated materials, employing the OoC with biomedical approaches will be a promising methodology in the healthcare industry.

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