Bioinspired Architected Materials for Aging‐Competent Brain Organoids: Multiscale Design, Assembly, and Translation

Human brain organoids provide models of neural development and disease, but their developmentally young state and incompletely organized microenvironment limit the reconstruction of late‐life neural tissue. This review frames aging‐competent brain organoids as biohybrid architected systems in which cellular composition, extracellular matrices, material interfaces, transport pathways, and sensing or actuation modules are organized across length scales. An architecture–property–exposure–function framework is developed to connect matrix mechanics and ligand presentation, bioelectronic interfaces, vascular and oxygen‐regulating systems, redox‐active materials, programmable carriers, and nanosensors with tissue responses. Aging competence is defined as the capacity of a mature organoid to undergo reproducible, cell‐type‐resolved age‐associated transitions and to exhibit a progressive loss of homeostatic reserve after calibrated challenge. Accordingly, material‐enabled phenotypes are evaluated through molecular age, organelle flux, neurovascular and immune states, network performance, and challenge–recovery behavior, while excluding hypoxia, necrosis, acute toxicity, and material persistence as dominant explanations. The resulting design logic links multiscale assembly and multifunctionality to disease‐matched models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis/frontotemporal degeneration, and Huntington's disease, as well as to nanomedicine screening and translational qualification. Treating the organoid–material construct as an integrated architecture establishes functional materials as controllable modules for building, perturbing, monitoring, and therapeutically interrogating human brain aging.