Although model organisms have provided insight into the earliest stages of cardiac and hepatic vascularization, we know very little about this process in humans because of ethical restrictions and the technical difficulty of obtaining embryos during very early development. In this study, we demonstrate that micropatterned human pluripotent stem cell–derived gastruloids enable in vitro modeling of the earliest stages of vascularization. We identify a combination of vascular-inducing factors that give rise to cardiac vascularized organoids with a spatially organized and branched vascular network. To show the broader utility of our vascularization strategy, we use the same vascular-inducing factors to produce hepatic vascularized organoids. Our results suggest that a conserved developmental program generates the vasculature within different types of organs.

In this review, we explore the growing role of artificial intelligence (AI) in advancing the biomedical applications of human pluripotent stem cell (hPSC)‐derived organoids. Stem cell‐derived organoids, these miniature organ replicas, have become essential tools for disease modeling, drug discovery, and regenerative medicine. However, analyzing the vast and intricate datasets generated from these organoids can be inefficient and error‐prone. AI techniques offer a promising solution to efficiently extract insights and make predictions from diverse data types generated from microscopy images, transcriptomics, metabolomics, and proteomics. This review offers a brief overview of organoid characterization and fundamental concepts in AI while focusing on a comprehensive exploration of AI applications in organoid‐based disease modeling and drug evaluation. It provides insights into the future possibilities of AI in enhancing the quality control of organoid fabrication, label‐free organoid recognition, and three‐dimensional image reconstruction of complex organoid structures. This review presents the challenges and potential solutions in AI‐organoid integration, focusing on the establishment of reliable AI model decision‐making processes and the standardization of organoid research.

Organoid Intelligence ushers in a new era by seamlessly integrating cutting-edge organoid technology with the power of artificial intelligence. Organoids, three-dimensional miniature organ-like structures cultivated from stem cells, offer an unparalleled opportunity to simulate complex human organ systems in vitro. Through the convergence of organoid technology and AI, researchers gain the means to accelerate discoveries and insights across various disciplines. Artificial intelligence algorithms enable the comprehensive analysis of intricate organoid behaviors, intricate cellular interactions, and dynamic responses to stimuli. This synergy empowers the development of predictive models, precise disease simulations, and personalized medicine approaches, revolutionizing our understanding of human development, disease mechanisms, and therapeutic interventions. Organoid Intelligence holds the promise of reshaping how we perceive in vitro modeling, propelling us toward a future where these advanced systems play a pivotal role in biomedical research and drug development.

Stem cell therapy has shown promise for treating myocardial infarction via re-muscularization and paracrine signalling in both small and large animals. Non-human primates (NHPs), such as rhesus macaques (Macaca mulatta), are primarily utilized in preclinical trials due to their similarity to humans, both genetically and physiologically. Currently, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are delivered into the infarcted myocardium by either direct cell injection or an engineered tissue patch. Although both approaches have advantages in terms of sample preparation, cell–host interaction, and engraftment, how the iPSC-CMs respond to ischaemic conditions in the infarcted heart under these two different delivery approaches remains unclear. Here, we aim to gain a better understanding of the effects of hypoxia on iPSC-CMs at the transcriptome level. NHP iPSC-CMs in both monolayer culture (2D) and engineered heart tissue (EHT) (3D) format were exposed to hypoxic conditions to serve as surrogates of direct cell injection and tissue implantation in vivo, respectively. Outcomes were compared at the transcriptome level. We found the 3D EHT model was more sensitive to ischaemic conditions and similar to the native in vivo myocardium in terms of cell–extracellular matrix/cell–cell interactions, energy metabolism, and paracrine signalling. By exposing NHP iPSC-CMs to different culture conditions, transcriptome profiling improves our understanding of the mechanism of ischaemic injury.

Conductive polymers (CPs) have gained increasing attention in cardiac tissue engineering (CTE) due to their ability to restore electrical conductivity, enhance cardiomyocyte (CM) function, and support tissue regeneration. Despite significant progress in the field, challenges related to variability in biocompatibility testing, including dopant-dependent cytotoxicity, poor reporting of biodegradability, unpredictable long-term stability, and regulatory uncertainty of CPs continue to hinder their applications. To address this, we reviewed the properties, applications, and biocompatibility of the three most studied CPs: polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT), and polyaniline (PANI) in CTE, and contrast their advantages and safety challenges with inorganic electrodes and carbon-based materials. We critically assessed current methods for evaluating the biocompatibility of CPs, highlighting limitations in traditional in vitro and in vivo approaches. Our analysis revealed a significant gap in chronic implantation data beyond six months and provided dopant-centered assessment and toxicity risks across different CP platforms. A comprehensive roadmap was further suggested to guide the evaluation of the biocompatibility of CPs, including material characterization, in vitro cytotoxicity testing with particular emphasis on in vitro 3D human heart model testing platforms of human pluripotent stem cell (hPSC)-derived engineered heart tissues and cardiac organoids, and in vivo evaluation. Additionally, we discussed recent advances in improving the biocompatibility of CPs through hybrid scaffold development, molecular engineering, surface chemistry modifications, and the development of stimuli-responsive and targeted CP constructs. By establishing this standardized framework and highlighting critical regulatory requirements, this review aims to overcome current biocompatibility barriers and facilitate the improved implementation of CPs in CTE applications.