Advancing Personalized Cardiac Organoids - Converging In Vitro, In Chemico, and In Silico Models - Project Summary/Abstract Cardiac disease remains the leading cause of mortality, yet existing models fail to capture the complexity necessary for effective therapeutic development. COIN (Cardiac Organoids in Niches) integrates in silico, in chemico, and in vitro methodologies to engineer patient-specific cardiac niches, enhancing disease fidelity and therapeutic screening. By leveraging AI-driven modeling, biomaterials engineering, and multi-omics analysis, COIN establishes a scalable, reproducible NAMs platform for disease modeling and drug discovery. COIN’s AI- powered niche design tailors cardiac microenvironments to genetic, sex, and age profiles, improving disease relevance and therapeutic predictability. Innovations in biomaterials engineering refine extracellular matrix (ECM) properties to replicate human cardiac physiology, while organoid villages enhance translational accuracy. Multi- scale validation ensures COIN models faithfully reproduce patient-specific disease phenotypes, supporting regulatory qualification and preclinical safety assessment. COIN collaborates with the VQN to establish regulatory validation benchmarks and with the NDHCC to facilitate FAIR-compliant multi-omics data-sharing. Supported by the nation’s largest academic iPSC biobank and the Stanford Center for Genomics and Personalized Medicine, COIN unites leading experts in bioinformatics, AI, biomaterials, and organoid engineering to develop standardized, regulatory-ready NAMs models. Comprehensive technical characterization ensures functional validation, disease fidelity, and industry readiness. Training and outreach initiatives drive interdisciplinary collaboration and workforce development, fostering broad industry adoption. By integrating multi-scale modeling, high-throughput biomaterials engineering, and AI-driven analytics, COIN reduces reliance on animal models, advances precision drug discovery, and establishes a gold-standard NAMs platform for cardiac medicine.
