Engineered organoid platforms for drug delivery evaluation

Advanced biomaterials and drug delivery systems (DDSs) require human-relevant models that can capture tissue heterogeneity, physiological barriers, and patient-specific therapeutic responses. Conventional two-dimensional cultures and animal models often fail to reproduce these features, contributing to discrepancies between preclinical evaluation and clinical outcomes. Organoids offer three-dimensional, multicellular platforms that partially recapitulate the architecture and functions of human tissues and therefore provide new opportunities for evaluation of material-tissue interactions. This review first outlines the major types of organoids derived from adult stem cells, pluripotent stem cells, and patient tissues. It then discusses engineering strategies, particularly organoid-on-a-chip systems and 3D bioprinting, that introduce controlled fluid flow, mechanical cues, tissue interfaces, and spatial organization to improve physiological relevance, reproducibility, and screening compatibility. Particular emphasis is placed on the emerging use of organoids for assessing DDSs, including tissue penetration, cellular uptake, transport across mucus and blood-brain barrier models, targeting specificity, therapeutic efficacy, and nanomaterial-associated toxicity. Finally, we examine current challenges, including model standardization, vascularization, immune and stromal integration, quantitative validation, scalability, reproducibility, and cost. Integration with defined biomaterials, microfluidics, automated manufacturing, real-time sensing, and computational analysis may establish organoids as complementary and increasingly predictive platforms for biomaterial evaluation, DDS development, safety assessment, and personalized therapy.