2025-06-24 2025, Volume 1 Issue 2

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  • research-article
    Quan-Jing Mei, Jia-Qi Wen, Xiao-Xiao Xu, Hui-Qi Xie

    Brain organoids have become important tools for studying neural development and disease modeling by closely mimicking in vivo brain architecture and function. However, despite their potential, conventional brain organoids lack a vascular system, limiting their physiological relevance and growth due to restricted oxygen and nutrient supply. Recent advances in generating vascularized brain organoids (V-Organoids) have sought to overcome such limitations, allowing for more accurate modeling of human brain development, neurovascular interactions, and blood- brain barrier (BBB) function. This article provides a comprehensive review of the methodologies employed to enhance the vascularization of brain organoids, including induction techniques, biomaterials, advanced bioengineering approaches, and in vivo implantation. The introduction of functional vasculature into brain organoids has not only enhanced their survival and maturation but also expanded their utility in disease modeling, drug screening, and regenerative medicine. We also discuss the applications of V-Organoids in the study of neurodevelopmental processes, BBB permeability in neurological disorders, brain cancer, and regeneration applications. Despite significant progress made in the development of V-Organoids, challenges such as vascular maturity, immune integration, longevity, and ethical considerations must be addressed to enable more accurate brain models, which could enhance our understanding of neurodevelopment and potential treatments.

  • research-article
    Yuxin Jin, Qizhu Chen, Longhui Gong, Xinfeng Zheng, Linjie Chen, Bo Li, Hao Zhou, Kenny Yat Hong Kwan, Ouqiang Wu, Zitian Zheng, Morgan Jones, Yuting Huang, Dilhana S. Badurdeen, Yikun Chen, Kai Chen, Sunren Sheng, Shengdan Jiang, Aimin Wu

    Repair and regeneration of tissues and organs remain central to medical research. Organoids, advanced models created through in vitro tissue engineering, enable stem cells to form three-dimensional structures that replicate organ tissues and function spontaneously. The advancement of organoid technology has greatly enhanced our understanding of disease progression and organ development. A crucial component of this technology is the development of appropriate scaffolds to support organoid growth. Recently, hydrogels have emerged as promising materials due to their excellent biocompatibility, tunability, and degradability, facilitating the in vitro culture of stem cells and their differentiation into various organoids. However, more complex organ models, which involve extensive intercellular and extracellular communication, present significant challenges for present research. Moreover, advancements in biomaterial fabrication and their integration with organoid technology remain underexplored. This review explores the pivotal role of hydrogels in organoid preparation, comparing the advantages and limitations of different hydrogel fabrication methods. It also highlights recent advancements in the application of organoid hydrogels across various biological systems and discusses future challenges and directions in this field.

  • research-article
    Fanjin Meng, Yang Yu, Jinshu Yu, Hong Chen, Yuwen Ma, Yonghao Chen, Yan Wang, Jingjing Jiang, Xi He, Zhongyan Zhan, Pingping Yan, Jing Wen, Lijuan Zhang, Wei Chen, Airong Qian, Xiaolan Guo, Bing Yang, Qi Liang, Guangrong Wang, Bin Guo, Chong Yin
    2025, 1(2): 25040003. https://doi.org/10.36922/OR025040003

    Bone-filling materials are critical tools for the treatment of bone defects. However, existing materials require improvements in tissue compatibility and drug-loading capacity. In this study, we designed and synthesized a novel trabeculae-like biomimetic bone-filling material (TBM) that mimics the composition and structure of natural bone trabecular tissue. This TBM demonstrated high mechanical strength and excellent biocompatibility. It effectively embedded osteogenic cells and potentially functioned as an organoid. We demonstrated that the TBM exhibited therapeutic efficacy in treating various bone defects and fractures by filling defect regions and enabling sustained release of small-molecule and nucleic acid drugs. Based on these findings, we propose TBM as a promising candidate for the treatment of bone defects and provide innovative insights for the development of bone-filling materials.

  • research-article
    Jian Wang, Zhidao Xia, Jiacan Su
    2025, 1(2): 25040005. https://doi.org/10.36922/OR025040005

    Organoid research has experienced significant advancements in 2024, revolutionizing the fields of disease modeling, drug discovery, and regenerative medicine. Key innovations include the refinement of culture protocols for generating more physiologically relevant organoids derived from a wide range of human tissues, facilitated by improved differentiation protocols for induced pluripotent stem cells and adult stem cells. These advancements have led to organoids that better mimic in vivo tissue architecture and function, making them more suitable for studying complex diseases. The integration of microfluidics and biomaterial scaffolds into organoid cultures has further enhanced the replication of organ-specific microenvironments. In addition, the application of cutting-edge genomic tools, such as CRISPR/Cas9 gene editing, single-cell RNA sequencing, and high-throughput screening, has enabled the generation of organoid models with precise genetic mutations, facilitating the exploration of disease mechanisms and the screening of therapeutic agents. Artificial intelligence and machine learning have played a pivotal role in analyzing organoid data, enabling high-throughput screening and the development of personalized treatment strategies. While challenges remain in scalability, reproducibility, and vascularization, the innovations made in 2024 have set the stage for future clinical applications of organoid technologies, offering new possibilities for personalized medicine, drug development, and regenerative therapies.

  • research-article
    Siyue Qin, Ju Gao, Mao Ding, Lauren H. Vicuna, Xinglong Wang
    2025, 1(2): 25040006-25040006. https://doi.org/10.36922/OR025040006

    Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the degeneration of dopaminergic (DA) neurons in the substantia nigra and the accumulation of α-synuclein aggregates, leading to motor and non-motor dysfunctions. The pathogenesis of PD involves a complex interplay of genetic mutations, environmental factors, and cellular mechanisms, including mitochondrial dysfunction, impaired proteostasis, neuroinflammation, and gut-brain axis dysregulation. Traditional research models, such as animal models and two-dimensional cell cultures, have provided valuable insights but often fall short in replicating the multifaceted and progressive nature of PD, especially in sporadic cases. The emergence of organoid technology offers a transformative approach to PD research. This technology enables the generation of three-dimensional structures that closely mimic the architecture, cellular composition, and functionality of the human midbrain. Midbrain organoids have become pivotal models for investigating disease mechanisms, including DA neuron degeneration, α-synuclein aggregation, and neuroinflammatory responses. Moreover, organoids enable high-throughput drug screening and the identification of potential therapeutic targets. Beyond modeling, recent advancements have demonstrated the feasibility of organoid transplantation as a therapeutic strategy. This review summarizes the current progression of organoid technology in PD research, focusing on its application in modeling pathomechanisms, drug discovery, and therapeutic applications. Despite being in its early stages, organoid technology holds significant promise for advancing our understanding of PD pathogenesis and developing translational therapies.

  • research-article
    Lu-Qi Cao, Yuhao Xie, Yuhong Liu, John Wurpel, Leli Zeng, Zhe-Sheng Chen
    2025, 1(2): 25050008. https://doi.org/10.36922/OR025050008

    Cancer remains one of the most pressing medical problems in the world. Recent years have seen a gradual rise in utilization of “organoids,” a novel in vitro three-dimensional culture technology, in cancer research. Organoids are multicellular structures derived from human stem cells, and cancer organoids can replicate the characteristics, morphology, and functionality of the original tumor in the human body. At present, organoid technology has been widely used in various oncologic contexts, including colorectal, liver, lung, pancreatic, and breast cancers, providing considerable assistance in patient-specific drug testing, precision medicine, and the development of personalized medical strategies. Therefore, this preclinical model contributes to significantly accelerating the translation from basic cancer research to clinical therapeutics. This review discusses the preparation of cancer organoids and their recent progress in multiple cancer research fields. Finally, the challenges of organoid technology in current clinical practice and future development prospects are discussed.

  • research-article
    Liangyu Guo, Yifan Xia, Panpan Pan, Jingdi Chen
    2025, 1(2): 25110011. https://doi.org/10.36922/OR025110011

    The bone marrow serves not only as a “factory” for hematopoiesis but also as a dynamic ecological “repository” regulating immune responses, metabolic processes, and disease progression. Its complexity stems from the three-dimensional interplay of vascular networks, mesenchymal stromal cells, hematopoietic stem cells, and immune cells -a spatial dynamism poorly captured by traditional models. Recently, the first functional human bone marrow organoids were constructed in vitro through multilineage differentiation and self-organization of induced pluripotent stem cells. This model accurately captures the key functional and structural characteristics of the human bone marrow hematopoietic niche, marking a significant milestone in advancing research on hematopoietic development and bone marrow diseases.

  • research-article
    Rui L. Reis
    2025, 1(2): 25210018. https://doi.org/10.36922/OR025210018