Recent advances in nanomaterial-based brain organoid on-a-chip for drug evaluation

Brain organoids have emerged as promising three-dimensional (3D) models that recapitulate key aspects of human brain development, neural circuit formation, and neurological disorders. However, conventional culture systems face critical limitations, including inadequate vascularization, restricted diffusion of nutrients and oxygen, insufficient neuronal maturation, and poor reproducibility, all of which hinder long-term stability and clinical translation. To address these challenges, organoid-on-a-chip technologies have been developed to provide controlled microenvironments, fluidic dynamics, and enhanced tissue integration; nevertheless, significant barriers remain. In recent years, nanomaterials have been increasingly incorporated into brain organoids and chip-based systems to overcome these limitations. Due to their unique structural, electrical, and biochemical properties, nanomaterials can mimic components of the extracellular matrix, promote cellular organization, enhance electrophysiological maturation, and enable advanced sensing modalities. Their integration with organoid-on-a-chip platforms further facilitates vascularization, supports long-term culture, and contributes to the generation of physiologically relevant neural models. This review provides a comprehensive overview of brain organoid technology, the functional roles of nanomaterials in these systems, and recent advances in nanomaterial-based brain organoid-on-a-chip platforms. Additionally, we summarize how these interdisciplinary approaches enhance the modeling of neurological diseases, improve drug evaluation including organoid-based biohybrid robot on-a-chip, and support the development of personalized medicine. Finally, we discuss persisting limitations and outline future directions toward the realization of intelligent, reproducible, and clinically translatable neural platforms. We hope this review will inspire innovative strategies and accelerate progress at the intersection of nanomaterials, organoid biology, and chip-based technologies, thereby advancing personalized and effective treatments in neuroscience and biomedicine.