2025-12-15 2025, Volume 1 Issue 4

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  • research-article
    Wei Wang, Tehan Zhang, Juehan Wang, Wenzhao Wang, Haijian Sun
    2025, 1(4): 025330027. https://doi.org/10.36922/OR025330027

    Bone organoids have emerged as powerful three-dimensional (3D) culture systems that recapitulate key aspects of bone physiology and pathology, offering superior translational relevance compared with traditional two-dimensional cultures and animal models. By integrating stem cell-derived lineages with biomimetic matrices that mimic the native extracellular matrix, bone organoids faithfully reproduce cellular heterogeneity, structural organization, and dynamic remodeling. Recent advances in natural and synthetic hydrogels, bioactive signaling, and diverse cell sources—including osteogenic, osteoclastic, hematopoietic, and adipogenic populations—have further enhanced organoid fidelity. Biofabrication strategies, such as scaffold-assisted assembly, 3D bioprinting, and organ-on-a-chip platforms enable spatial control and vascularization, while CRISPR-based gene editing and artificial intelligence-driven optimization offer unprecedented precision and scalability. The development of vascularized, innervated, and multi-system-integrated bone organoids holds great promise for disease modeling, drug screening, and regenerative therapies. This review outlines present strategies, technological advances, and future directions in bone organoid engineering.

  • research-article
    Tong Sun, Cheng Feng, Tian Huang, Rong Xu, Rong Yan, Chenghui Li, Zhongkai Wang, Jialiang Zheng, Khand Aftab Ahmed, Hao Lin, Jian Lu
    2025, 1(4): 025370029. https://doi.org/10.36922/OR025370029

    Metastasis is a primary cause of cancer-related mortality, and the liver is the most common site of tumor metastasis. The molecular heterogeneity and complex tumor microenvironment of liver metastases remain major barriers contributing to clinical treatment failure. The dearth of accurate metastatic liver tumor models leads to a paucity of understanding regarding the mechanisms of liver metastasis and limits the exploration of novel therapeutic approaches. Patient-derived organoids provide a three-dimensional, tissue-engineered, cell-based in vitro model that reproduces the complex structure and function of the corresponding in vivo tissue. The advent of this personalized paradigm, tailored to the specific needs of individual patients, has enabled the translation of Foundational research into clinical applications. This review provides a comprehensive summary of various methods for culturing liver metastatic cancer organoids, highlighting the novel findings and clinical applicability of organoids in liver metastasis research. It also discusses current research achievements and recent advances in liver metastatic cancer organoids.

  • research-article
    Ting Cheng, Wojciech Chrzanowski, Han Liu, Jiacan Su
    2025, 1(4): 025450031. https://doi.org/10.36922/OR025450031

    Organoids are models of miniature organs formed by three-dimensional (3D) culture of stem cells or primary tissue cells. Their structure or function is highly similar to that of in-situ organs. Extracellular vesicles (EVs) are non-replicating nanocarriers with a phospholipid bilayer (20 - 400 nanometers) used to deliver bioactive substances. Organoid-derived extracellular vesicles (OEVs) are easier to form than conventional EVs and have enhanced biological functions. Organoids have the characteristics of stem cells; the transportation of bioactive substances by OEVs has broad prospects in medical applications. This article expounds the development, concept, construction methods and applications of organoids, describes the types, research progress and advantages of EVs, then outlines the concept of the basic biology of EVs, and explores their potential applications in disease treatment and intervention. Furthermore, we examine the distinctions that differentiate OEVs from conventional EVs. Finally, this paper summarises the advantages and challenges of OEVs and outlines their future prospects in disease treatment.

  • research-article
    Yu Yang, Yu-Bo Wang, Hao Yin, Ling-ling Xian, Jia Cao, Zhen-Xing Wang, Hui Xie
    2025, 1(4): 025450032. https://doi.org/10.36922/OR025450032

    Aging, as a process of gradual decline in cellular and tissue function, poses a major challenge for healthcare systems worldwide. However, traditional models (experimental animals and 2D cell cultures) struggle to reproduce the complexity of human aging, which limits the depth of mechanistic understanding. Organoids, defined as self-organizing 3D stem cell-derived structures that replicate key organ features, have effectively addressed this research gap. This article reviews the applications of organoids in the study of aging, including their core principles, methods for generating common organoid types, advantages, and limitations. The validation processes and mechanisms of the aging model are also discussed. In addition, the applications of brain organoids in research on Alzheimer’s disease and Parkinson’s disease, heart organoids in research on myocardial aging, and liver and islet organoids in research on diabetes are emphasized. Despite advances in single-cell sequencing, gene editing, and imaging technologies, challenges such as standardization and vascularization remain. Nevertheless, organoids have accelerated the development of anti-aging drugs and personalized medicine, thus becoming indispensable tools for understanding the mechanisms of human aging and developing interventions to extend healthy life span.

  • research-article
    Qiongjiao Zeng, Denghui Xie, Di Wang, Chao Zheng, Liu Yang, Mario Rothbauer, Yiting Lei, Zhong Alan Li
    2025, 1(4): 025450033. https://doi.org/10.36922/OR025450033

    Age-related deterioration of the musculoskeletal (MSK) system drives loss of mobility, lower quality of life, and escalates healthcare costs in older adults. Organoids are three-dimensional, self-organizing constructs that recapitulate key aspects of tissue architecture and function, providing a promising platform to model human MSK aging with higher physiological relevance than conventional two-dimensional cultures and many animal models. Current reliance on decellularized extracellular matrices as scaffolds constrains reproducibility and limits the ability to tune biochemical and biophysical cues. In contrast, engineered matrices allow for precise control over composition, mechanics, and degradability, thereby supporting organoid formation, maturation, and the induction of aging-related phenotypes. This review specifically focuses on MSK organoids and presents a conceptual synthesis linking biomaterial parameters to core MSK aging hallmarks and functional validation assays. We synthesize current strategies for constructing aging MSK organoids and delineate biomaterials design principles to recapitulate aged MSK microenvironments. We examine the key structural, mechanical, and biochemical material properties that influence organoid formation and the establishment of an aging-related microenvironment. Finally, we discuss smart material platforms and strategies for multi-tissue integration, assessing their potential to facilitate the exploration of mechanistic insights and therapeutic testing, as well as to enhance the accuracy and translational relevance of in vitro aging models.

  • research-article
    Tao Qian, Jiazhou Wu, Zexian Liu, Aiyuan Wang, Yanbin Wu, Junli Wang, Hongyu Jiang, Zhengrui Zhou, Cheng Huang, Yazhou Li, Junming Zhang, Biao Ma, Yun Bai, Jialiang You, Endong Luo, Dingkai Wang, Ying He, Jiang Peng
    2025, 1(4): 025480037. https://doi.org/10.36922/OR025480037

    Osteoarthritis (OA) is closely associated with subchondral bone (SCB) degeneration; however, current models fail to adequately mimic its complex microenvironment. Here, we developed a self-organizing subchondral bone organoid (SSBO) by co-culturing stromal vascular fraction (SVF) cells with decellularized cartilage extracellular matrix (CECM). SVF provided cellular heterogeneity, including adipose-derived stem cells (ADSCs), endothelial cells, pericytes, and macrophages, while CECM served as a native scaffold with tissue-specific cues. SSBO exhibited spontaneous spheroid formation, active cellular infiltration, and dynamic matrix remodeling. Compared to ADSC-only controls, SSBO showed enhanced cell viability, vascularization, collagen remodeling, and spatial organization. Immunostaining and qPCR analyses confirmed an endochondral ossification-like process, characterized by the sequential expression of SOX9, COL2A1, RUNX2, COL1A1, and OCN. In vivo implantation into immunodeficient mice demonstrated robust angiogenesis, bone-like tissue formation, and integration with host vasculature. Furthermore, in a mouse osteochondral defect model, SSBO significantly promoted repair, with improved bone volume, trabecular architecture, and cartilage regeneration. Collectively, this study presents a novel strategy for constructing vascularized, immunomodulatory, and osteogenic SCB organoids, offering a promising platform for regenerative medicine and bone-cartilage interface repair.