Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems that recapitulate patient-like pathophysiology are emerging as alternatives to conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types of ND, discuss the general strategy to modelling NDs using a microfluidic chip, and introduce the organoid-on-a-chip as the next advanced relevant model. Lastly, we overview how these models are being applied in academic and industrial drug development. The integration of microfluidic chips, stem cells, and biotechnological devices promises to provide valuable insights for biomedical research and developing diagnostic and therapeutic solutions for NDs.

The evolution of preclinical in vitro cancer models has led to the emergence of human cancer-on-chip or microphysiological analysis platforms (MAPs). Although it has numerous advantages compared to other models, cancer-on-chip technology still faces several challenges such as the complexity of the tumor microenvironment and integrating multiple organs to be widely accepted in cancer research and therapeutics. In this review, we highlight the advancements in cancer-on-chip technology in recapitulating the vital biological features of various cancer types and their applications in life sciences and high-throughput drug screening. We present advances in reconstituting the tumor microenvironment and modeling cancer stages in breast, brain, and other types of cancer. We also discuss the relevance of MAPs in cancer modeling and precision medicine such as effect of flow on cancer growth and the short culture period compared to clinics. The advanced MAPs provide high-throughput platforms with integrated biosensors to monitor real-time cellular responses applied in drug development. We envision that the integrated cancer MAPs has a promising future with regard to cancer research, including cancer biology, drug discovery, and personalized medicine.

Background: Glioblastoma (GBM) progression is driven by intricate interactions between neoplastic cells and immune populations within the tumor microenvironment (TME), yet the temporal organization of these processes remains insufficiently defined. While tumor-associated macrophages (TAMs), composed of microglia and monocyte-derived macrophages, constitute a major immune population in GBM, microglia play a prominent role in shaping local immunosuppressive niches, thereby limiting cytotoxic lymphocyte infiltration. However, static co-culture models constrain interrogation of dynamic tumor-immune signaling. Methods: We utilized a programmable multi-inlet microfluidic platform that allows sequential, order-specific introduction of immune cells into GBM constructs, enabling controlled interrogation of MG- and natural killer (NK)–mediated interactions under defined temporal conditions. Bulk transcriptomic profiling and single-cell analyses were used to characterize tumor- and immune-associated pathways elicited by distinct temporal configurations. Results: In triculture constructs containing identical populations of GBM cells, microglia, and NK cells, MG-first delivery preferentially activated STAT3-associated immunoregulatory transcriptional programs, whereas NK-first delivery induced cytotoxic and interferon-related gene expression profiles. IL12A expression was selectively increased under NK-first conditions and correlated with immune-active GBM states in patient datasets. STAT3 inhibition reduced MG-associated suppression, increased IL12A expression, and enhanced the response to temozolomide. Conclusions: This programmable spheroid platform not only recapitulates hallmark features of the GBM immune microenvironment but also uncovers temporally regulated pathways arising from sequential cellular interactions. By enabling controlled reconstruction of dynamic tumor-immune signaling, this system offers a versatile strategy for mechanistic investigation and provides a foundation for evaluating immune-modulatory approaches and microenvironment-targeted interventions in GBM and other malignancies.