Bone/cartilage organoids have garnered significant attention in regenerative medicine due to their promising applications in tissue repair and disease modeling. Despite this growing interest, there is still a gap in understanding global research trends and developments in this field. This study provides a comprehensive review of the present status and emerging directions of bone/cartilage organoid research worldwide. Utilizing data from 288 records in the Web of Science Core Collection (2010 - 2024), we employed R, VOSviewer, CiteSpace, and GraphPad Prism to analyze the literature’s historical development, general characteristics, and keyword distributions. The analysis revealed a steady increase in publications since 2010, peaking in 2023, with the United States leading in contributions, and Bioactive Materials as the most influential journal. Noteworthy authors included Jiacan Su from China and Hans Clevers from the Netherlands. Research subareas were clustered into seven themes: Regenerative Medicine, Bone Regeneration, Bone Marrow Organoids, Differentiation, Extracellular Matrix, Expression, and Protein-Based Culture. Four main research directions were identified: stem cells and the microenvironment, biomaterials, regenerative medicine, and disease modeling/drug screening. This first bibliometric study on bone/cartilage organoids establishes a knowledge map, identifies key trends, and pinpoints potential hotspots, offering valuable insights for future research in this evolving field.

This article examines the role of brain organoids in understanding neurodevelopmental disorders (NDDs), including autism spectrum disorder, intellectual disabilities, and schizophrenia, which arise from disruptions in the complex processes of brain development. The transformative potential of human pluripotent stem cell-derived brain organoids as models for investigating the molecular mechanisms underlying NDDs and their implications for therapeutic innovation is explored. By simulating critical stages of human brain development - such as neurulation, neurogenesis, and gliogenesis - organoids provide a physiologically relevant platform to investigate cellular diversity, synaptic connectivity, and neuronal circuit formation. Advanced methodologies, including single-cell RNA sequencing and chromatin accessibility profiling, are utilized to dissect lineage-specific gene expression patterns and regulatory mechanisms within organoids. In addition, metabolic profiling and functional assessments comprehensively evaluate neuronal maturation, synaptic plasticity, and cellular interactions, addressing the limitations of traditional two-dimensional cultures. This article also examines the influence of environmental factors, such as viral infections, by utilizing organoid models to simulate host-pathogen interactions and assess their impact on neural progenitor function and cortical development. The integration of machine learning and innovative culture systems, including microfluidic and vascularized models, enhances the physiological relevance and reproducibility of brain organoid research. This review highlights the potential use of organoids in elucidating the molecular pathology of NDDs and as platforms for drug discovery and personalized therapeutic screening, ultimately bridging molecular insights with therapeutic applications and underscoring the vital role of brain organoids in advancing the understanding of NDDs and facilitating the development of targeted interventions.

Organoid technology has transformed precision medicine by enabling patient-specific 3D models that replicate tissue complexity, facilitating high-throughput antisense oligonucleotide (ASO) therapeutic screening. Patient-derived organoids retain donor-specific genetic and phenotypic profiles, offering physiologically relevant platforms for modeling diseases, such as Duchenne muscular dystrophy (DMD). For example, DMD cardiac organoids rapidly identify dystrophin-restoring ASOs through a 6-week validation pipeline, overcoming limitations of 2D cultures by preserving multicellular interactions. Challenges include expanding tissue representation (e.g., skeletal muscle in DMD), enhancing ASO pharmacokinetic modeling in avascular organoids, and standardizing protocols to minimize variability. Future integration of vascularized or organ-on-chip models, multi-tissue assembloids, and artificial intelligence-driven screening could improve predictive accuracy. Chemically optimized ASOs with reduced off-target effects, combined with clustered regularly interspaced short palindromic repeats-based editing, may synergistically enhance therapeutic precision. As regulatory frameworks adapt to incorporate organoid-based validation, this technology accelerates personalized drug discovery for genetic disorders. Addressing present limitations through bioengineering and standardization will solidify organoids as critical tools for tailoring precision therapies to individual patient needs.

As critical connective tissues transmitting from muscles to bones, tendons play a central role in movement and postural stability. However, their low cellularity, limited metabolic activity, and propensity for degeneration render them vulnerable to acute and chronic injuries. Traditional therapeutic approaches, such as autografts and allografts, are constrained by donor scarcity, immune rejection, and suboptimal functional recovery, driving the emergence of tissue engineering and organoid technologies as innovative solutions. Tendon organoids, which recapitulate the native tendon’s three-dimensional (3D) structure, cellular complexity, and biomechanical niche, offer a physiologically relevant in vitro model for advancing our understanding of tendon development and pathology. This comprehensive review systematically examines recent advances in tendon organoid research, highlighting four key determinants in the construction of tendon organoids: (i) Selection and optimization of cell sources, particularly tendon stem/progenitor cells; (ii) regulation of biochemical cues through spatiotemporal coordination and signaling pathway modulation; (iii) design of biomimetic 3D microenvironments, including physical scaffolds and mechanical stimulation; and (iv) integration of engineering strategies, such as single-cell omics, gene editing, 3D bioprinting, and artificial intelligence (AI) for system optimization. Notably, tendon organoids demonstrate multidimensional potential in translational applications, including regenerative medicine, disease modeling, drug screening, and biomechanical research. To overcome current technical bottlenecks, future investigations should prioritize AI-driven organoid design, standardized manufacturing protocols, and solutions for clinical translation challenges. By bridging Fundamental research and clinical therapeutics, this review outlines a theoretical framework and technical roadmap for the refined construction and application of tendon organoids, highlighting their transformative potential in regenerative medicine and precision healthcare.

Bone metastasis presents a major challenge in oncology, often involving prolonged tumor dormancy within the complex bone marrow microenvironment (BMME). This dormancy, characterized by halted proliferation but sustained viability, poses risks for late recurrence and therapy resistance. Recent advancements in bone marrow-on-a-chip (BMOC) technology provide highly controllable, physiologically relevant biomimetic platforms to model the intricate cellular and molecular interactions governing BMME-regulated dormancy. This review focuses on BMOC-based approaches, examining their principles, distinct advantages, applications, and key findings in elucidating mechanisms of tumor dormancy regulation. Critically, it addresses current technical and biological limitations of BMOCs (e.g., replicating full immune component complexity) and propose concrete future directions for enhancing BMOC development and integration with complementary technologies. Enhanced understanding through refined BMOC technology could Fundamentally uncover dormancy mechanisms and advance novel therapeutic strategies for metastatic control.

Musculoskeletal (MSK) disorders represent a leading cause of disability worldwide, with their incidence increasing steadily each year. While animal models have been instrumental in replicating various aspects of MSK pathologies, they face significant limitations, including interspecies variations, ethical concerns, and prolonged modeling timelines. The emergence of MSK organoids presents promising complementary models for pathophysiological research, disease modeling, drug screening, and regenerative medicine. As a valuable adjunct for traditional two-dimensional cultures and animal experiments, organoids provide novel mechanistic insights into MSK biology in a more physiologically relevant context. This review provides a comprehensive overview of current modeling strategies for MSK diseases and highlights the potential of organoids to reduce reliance on animal models. We critically assess the advantages and limitations of MSK organoids in disease recapitulation, identify key challenges in their development, and propose potential strategies for refinement. Finally, future directions and opportunities in this rapidly evolving field have been discussed.

Rotator cuff injury is a common disease of the locomotor system, causing a serious burden on the individual patient as well as society. The current treatment primarily involves surgical intervention, but it cannot completely restore the physiological integrity of the rotator cuff and carries a significant risk of postoperative re-tear. To improve the repair of rotator cuff injuries, regenerative medicine strategies have been widely explored. Organoids refer to three-dimensional (3D) tissue structures derived from stem/progenitor cells in vitro, which recapitulate native organ structure and function, providing an emerging platform for disease modeling, drug screening, and regenerative medicine. In this paper, we first outline the disease background of rotator cuff anatomy and current clinical treatments and subsequently summarize fabrication strategies for the rotator cuff-relevant organoids, focusing on skeletal muscle, tendon, bone, cartilage, and especially regenerative medicine approaches for the tendon-bone interface. Building upon this Foundation, we describe in detail the integrative strategies for rotator cuff organoid biofabrication, encompassing cell sources, matrix materials, construction techniques, and strategies. Finally, this work also addresses the challenges in rotator cuff organoid construction and outlines possible solutions, while re-emphasizing the transformative potential of rotator cuff organoids for promoting Fundamental research, accelerating drug screening, and enabling functional repair of rotator cuff diseases.