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Drug-induced cardiotoxicity is a significant contributor to drug recalls, primarily attributed to limitations in existing drug screening platforms. Traditional heart-on-a-chip platforms often employ metallic electrodes to record cardiomyocyte electrical signals. However, this approach hinders direct cardiomyocyte morphology observation and typically yields limited functionality. Consequently, this limitation may lead to an incomplete understanding of cardiomyocyte characteristics. To address these challenges, we introduce a multifunctional cardiac microphysiological system featuring transparent indium tin oxide electrodes. This innovative design aims to overcome the limitations of conventional heart-on-a-chip systems where metal electrodes interfere with the observation of cells and increase the difficulty of subsequent image processing of cell images. In addition to facilitating optical measurement combined with image processing capabilities, this system integrates a range of electrodes with diverse functionalities. These electrodes can realize cellular electrical stimulation, field potential monitoring, and impedance change tracking, enabling a comprehensive investigation of various cardiomyocyte traits. To demonstrate its versatility, we investigate the effects of four cardiac drugs with distinct pharmacological profiles on cardiomyocytes using this system. This platform provides a means for quantitatively and predictively assessing cardiac toxicity, which could be applied to conduct a comprehensive evaluation during the drug discovery process. [ABSTRACT FROM AUTHOR]

In vitro organoid models, typically defined as 3D multicellular aggregates, have been extensively used as a promising tool in drug screening, disease progression research, and precision medicine. Combined with advanced microfluidics technique, organoid-on-a-chip can flexibly replicate in vivo organs within the biomimetic physiological microenvironment by accurately regulating different parameters, such as fluid conditions and concentration gradients of biochemical factors. Since engineered organ reconstruction has opened a new paradigm in biomedicine, innovative approaches are increasingly required in micro-nano fabrication, tissue construction, and development of pharmaceutical products. In this Perspective review, the advantages and characteristics of organoid-on-a-chip are first introduced. Challenges in current organoid culture, extracellular matrix building, and device manufacturing techniques are subsequently demonstrated, followed by potential alternative approaches, respectively. The future directions and emerging application scenarios of organoid-on-a-chip are finally prospected to further satisfy the clinical demands. [ABSTRACT FROM AUTHOR]

In recent years, advances in microfabrication technology and tissue engineering have propelled the development of a novel drug screening and disease modelling platform known as organoid-on-a-chip. This platform integrates organoids and organ-on-a-chip technologies, emerging as a promising approach for in vitro modelling of human organ physiology. Organoid-on-a-chip devices leverage microfluidic systems to simulate the physiological microenvironment of specific organs, offering a more dynamic and flexible setting that can mimic a more comprehensive human biological context. However, the lack of functional vasculature has remained a significant challenge in this technology. Vascularisation is crucial for the long-term culture and in vitro modelling of organoids, holding important implications for drug development and personalised medical approaches. This review provides an overview of research progress in developing vascularised organoid-on-a-chip models, addressing methods for in vitro vascularisation and advancements in vascularised organoids. The aim is to serve as a reference for future endeavors in constructing fully functional vascularised organoid-on-a-chip platforms., Competing Interests: Conflicts of interest statement: The authors have no conflicts to disclose.