The inner ear is essential for auditory perception and balance, yet damage to cochlear hair cells remains a major cause of irreversible hearing loss worldwide. As the number of individuals affected by sensorineural deafness continues to rise, there is a growing need for deeper pathophysiological insight and the development of effective therapies. Inner ear organoids, which recapitulate key aspects of the in vivo inner ear microenvironment, have emerged as powerful platforms for disease modeling, high-throughput drug screening, and regenerative medicine. This review summarizes recent progress in the development of inner ear organoids, with a focus on strategies to improve their structural complexity and functional maturity. In particular, we highlight innovations in vascularization and three-dimensional bioprinting that are advancing organoid scalability and integration potential. Meanwhile, commonly used biomaterials in three-dimensional bioprinting for inner ear organoids are systematically compared. Finally, we discuss current challenges and future directions for translating these technologies into clinical applications.

Organoids have attracted increasing attention from academia, industry, and regulatory agencies. At the turn of 2025-2026, we review recent breakthroughs in organoid technology and outline the major challenges currently faced in the field. We encourage broader participation to advance organoid technologies, overcome key bottlenecks, and further enable applications in disease research and innovative drug development.

The growth of the global older population has necessitated the development of advanced models to investigate biological processes in aging and to explore viable anti-aging strategies. This review focuses on two objectives: First, to explore organoid technology as a paradigm for observing and intervening in human aging, and second, to examine the possible overlaps and crossroads between organoid-based biomedical paradigms and traditional Chinese medicine (TCM). Recent advancements in this field have increased the physiological relevance of organoids, incorporating both a dynamic microenvironment and multi-organ interactions. Such accomplishments have enhanced the accuracy of models of neurodegeneration, cardiovascular deterioration, metabolic diseases, and age-related conditions. In addition to pharmacological and genetic treatments, organoid models offer new opportunities to study well-known anti-aging techniques, such as those that rely on the TCM system, which aims to balance the body using natural substances with antioxidant and repair properties. Together, organoid-based aging research and mechanistic evaluation of TCM-derived compounds may help identify interventions that support healthy aging.

Programmable organoids refer to organoid systems in which developmental trajectories are experimentally influenced by engineered genetic, epigenetic, material, or computational interventions. At present, these systems are dominated by externally imposed and feedback-limited control strategies rather than internally implemented or autonomous developmental architectures. Traditional organoids rely on spontaneous self-organization, but this intrinsic variability limits reproducibility, causal inference, and translational relevance. Recent advances in Clustered Regularly Interspaced Short Palindromic Repeats-based transcriptional and epigenetic engineering, optogenetic and chemogenetic patterning technologies, reaction-diffusion design, and real-time biosensing now allow developmental trajectories to be biased, stabilized, and interrogated with increasing experimental precision, without enabling fully autonomous or self-correcting control. This review organizes these approaches into a tiered, evidence-based framework, spanning genetic circuit construction, epigenetic modulation, synthetic morphogenesis, multi-scale sensing, adaptive regulation, and artificial intelligence-guided design, explicitly distinguishing experimentally validated strategies from fragile, context-dependent implementations and conceptual architectures. Applications across human developmental biology, disease modeling, and regenerative medicine are highlighted, alongside the technical, biosafety, and ethical considerations associated with exploring increasingly structured, yet predominantly externally guided, approaches to developmental regulation. Collectively, programmable organoids are presented here not as autonomous developmental systems, but as experimentally steerable platforms whose capabilities and limitations are jointly shaped by biological variability, maturation constraints, and the need for external guidance.

Intratumoral heterogeneity, alongside the dynamic evolution of cancer cells, continues to pose principal obstacles to efficacious cancer therapies. Although patient-derived organoids (PDOs) represent the gold standard for recapitulating patient-specific histopathology, their full utility emerges only through integration with high-resolution molecular profiling. This review synthesizes recent progress in combining PDOs with multi-omics approaches—including genomics, single-cell transcriptomics, and spatial omics—to elucidate the underpinnings of therapeutic resistance. We initially explore how organoid genomic profiling can monitor clonal dynamics and subclonal selection under therapeutic pressure. Next, we underscore the contributions of single-cell RNA sequencing in delineating transcriptional plasticity, detecting infrequent drug-tolerant persister populations, and charting nongenetic adaptive pathways. Of particular importance, we address the nascent domain of spatial transcriptomics, which preserves the structural integrity of organoids to uncover how proximate cell-cell interactions and niche elements shield tumor cells from therapeutic insult. Through the fusion of these multifaceted datasets, we advance a novel paradigm that frames resistance not as a fixed binary state, but as a spatiotemporally evolving adaptive phenomenon. The review culminates in delineating the translational promise of this synergistic paradigm for devising combination regimens that concurrently address genetic aberrations and adaptive microenvironments.

Bone metastasis represents a frequent late-stage complication in cancers such as lung, breast, and prostate, severely affecting patients’ quality of life. Conventional two-dimensional cultures and animal models fail to recapitulate the complex bone microenvironment. Patient-derived organoids (PDOs) offer a physiologically relevant three-dimensional platform to recapitulate bone metastasis by preserving native tumor features and modeling tumor-bone interactions. This review systematically outlines the current methodologies for constructing bone metastatic organoid models, evaluates their applications, and identifies future directions. We describe the essential components of culture systems and critically discuss their strengths and limitations in modeling bone-specific signaling. Furthermore, we highlight the capacity of PDOs to elucidate key aspects of bone metastasis, including tumor cell adaptation to the osseous niche, bidirectional remodeling of the microenvironment, and the dynamic monitoring of disease progression. Bone organoids are also discussed as a means of establishing a standardized bone microenvironment, offering a controllable in vitro platform for investigating interactions between tumor cells and the bone matrix. Furthermore, we present the translational potential of organoids for informing individualized therapy selection, evaluating clinical drug sensitivity, and facilitating the development of organoid biobanks. Looking forward, the development of patient-specific “bone metastasis-on-a-chip” systems with artificial intelligence-driven digital twins may transform the research paradigm from experimental simulation to precision prediction, ultimately advancing personalized therapeutic strategies for bone metastatic disease.

Organoid technology has rapidly matured into a versatile three-dimensional in vitro platform capable of recapitulating key structural and functional features of native tissues. The field is increasingly driven by multidisciplinary integration, with research efforts shifting beyond simple cellular self-organization toward the reconstruction of complex physiological functions. Recent advances in bioengineering have provided organoids with more precisely controlled physical and chemical microenvironments. Approaches such as microfluidic platforms, synthetic biomaterials, and three-dimensional bioprinting enable the in vitro reconstruction of tissue-specific architectures. In addition, progress in vascularization strategies has alleviated longstanding challenges associated with nutrient delivery and metabolic waste removal in larger organoids. The development of assembloid systems further allows the modeling of inter-organ communication and complex physiological axes, expanding the scope of organoid-based studies beyond single-tissue contexts. Together, these technological innovations have substantially enhanced the utility of organoids in disease modeling, drug screening, and regenerative medicine. With continuous improvements in culture systems and the advancement of high-dimensional data analysis, organoids are increasingly serving as a critical bridge between fundamental research and clinical translation. In this review, we summarize the key developments in 2025 and highlight ten representative studies that exemplify recent practical breakthroughs, with the aim of providing useful insights and references for researchers working in this rapidly evolving area.