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2024 Issue 4 (Available Online: 2024-12-28)

    EDITORIAL
    Organoids: the future of disease modelling and therapeutics
    Dongyang Zhou, Zhidao Xia, Jiacan Su
    2024, 5(4):  335-336.  doi:10.12336/biomatertransl.2024.04.001
    Abstract ( 50 )   HTML ( 17)   PDF (100KB) ( 26 )  
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    REVIEW
    Yongtao Wang, Yan Hou, Tian Hao, Marta Garcia-Contreras, Guoping Li, Dragos Cretoiu, Junjie Xiao
    2024, 5(4):  337-354.  doi:10.12336/biomatertransl.2024.04.002
    Cardiac organoids including co-culture, aggregation, scaffolds, and geometries are used to detect cardiac functions. The relationship between the hearts and organoids is emphasised to evaluate the underlying mechanism of cardiac organoids in cardiac development and repair. Clinical potential is summarised to investigate key biological states of cardiac organoids.
    Abstract ( 88 )   HTML ( 17)   PDF (2303KB) ( 45 )  
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    Cardiovascular diseases cause significant morbidity and mortality worldwide. Engineered cardiac organoids are being developed and used to replicate cardiac tissues supporting cardiac morphogenesis and development. These organoids have applications in drug screening, cardiac disease models and regenerative medicine. Therefore, a thorough understanding of cardiac organoids and a comprehensive overview of their development are essential for cardiac tissue engineering. This review summarises different types of cardiac organoids used to explore cardiac function, including those based on co–culture, aggregation, scaffolds, and geometries. The self–assembly of monolayers, multilayers and aggravated cardiomyocytes forms biofunctional cell aggregates in cardiac organoids, elucidating the formation mechanism of scaffold–free cardiac organoids. In contrast, scaffolds such as decellularised extracellular matrices, three–dimensional hydrogels and bioprinting techniques provide a supportive framework for cardiac organoids, playing a crucial role in cardiac development. Different geometries are engineered to create cardiac organoids, facilitating the investigation of intrinsic communication between cardiac organoids and biomechanical pathways. Additionally, this review emphasises the relationship between cardiac organoids and the cardiac system, and evaluates their clinical applications. This review aims to provide valuable insights into the study of three–dimensional cardiac organoids and their clinical potential.

    Ruiqi Huang, Yanjing Zhu, Haokun Chen, Liqun Yu, Zhibo Liu, Yuchen Liu, Zhaojie Wang, Xiaolie He, Li Yang, Xu Xu, Yuxin Bai, Bairu Chen, Rongrong Zhu
    2024, 5(4):  355-371.  doi:10.12336/biomatertransl.2024.04.003
    Spinal cord organoids (SCOs), generated from stem cells through bioengineering, have seen advances in cell types, developmental patterning, and neural signalling. These advances allow SCOs to be applied in developmental research, genetic engineering, drug screening, regenerative medicine, and personalised medicine.
    Abstract ( 57 )   HTML ( 15)   PDF (1992KB) ( 38 )  
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    Stem cell–derived spinal cord organoids (SCOs) have revolutionised the study of spinal cord development and disease mechanisms, offering a three-dimensional model that recapitulates the complexity of native tissue. This review synthesises recent advancements in SCO technology, highlighting their role in modelling spinal cord morphogenesis and their application in neurodegenerative disease research. We discuss the methodological breakthroughs in inducing regional specification and cellular diversity within SCOs, which have enhanced their predictive ability for drug screening and their relevance in mimicking pathological conditions such as neurodegenerative diseases and neuromuscular disorders. Despite these strides, challenges in achieving vascularisation and mature neuronal integration persist. The future of SCOs lies in addressing these limitations, potentially leading to transformative impactions in regenerative medicine and therapeutic development.

    Jiawei Yang, Nicholas G. Fischer, Zhou Ye
    2024, 5(4):  372-389.  doi:10.12336/biomatertransl.2024.04.004
    This review emphasises the potential transformation of combining organoid technology with artificial intelligence (AI) in oral medicine. We reveal new possibilities for improving diagnostics and treatment planning by examining the development of organoids, discussing AI innovations and exploring advanced AI-integrated organoids to ultimately improve patient outcomes.
    Abstract ( 78 )   HTML ( 12)   PDF (5532KB) ( 38 )  
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    The convergence of organoid technology and artificial intelligence (AI) is poised to revolutionise oral healthcare. Organoids – three–dimensional structures derived from human tissues – offer invaluable insights into the complex biology of diseases, allowing researchers to effectively study disease mechanisms and test therapeutic interventions in environments that closely mimic in vivo conditions. In this review, we first present the historical development of organoids and delve into the current types of oral organoids, focusing on their use in disease models, regeneration and microbiome intervention. We then compare single–source and multi–lineage oral organoids and assess the latest progress in bioprinted, vascularised and neural–integrated organoids. In the next part of the review, we highlight significant advancements in AI, emphasising how AI algorithms may potentially promote organoid development for early disease detection and diagnosis, personalised treatment, disease prediction and drug screening. However, our main finding is the identification of remaining challenges, such as data integration and the critical need for rigorous validation of AI algorithms to ensure their clinical reliability. Our main viewpoint is that current AI–enabled oral organoids are still limited in applications but, as we look to the future, we offer insights into the potential transformation of AI–integrated oral organoids in oral disease diagnosis, oral microbial interactions and drug discoveries. By synthesising these components, this review aims to provide a comprehensive perspective on the current state and future implications of AI–enabled oral organoids, emphasising their role in advancing oral healthcare and improving patient outcomes.

    Chen Zhang, Yingying Jing, Jianhua Wang, Zhidao Xia, Yuxiao Lai, Long Bai, Jiacan Su
    2024, 5(4):  390-410.  doi:10.12336/biomatertransl.2024.04.005
    This review presents an overview of skeletal organoids, detailing core components, cell types, matrix gel options, and cytokine pathways. Applications include bone and cartilage repair, drug testing, toxicological testing, personalised medicine, and gene therapy research, emphasising their role in addressing conditions like fractures, osteoarthritis, and muscle atrophy.
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    The skeletal system, composed of bones, muscles, joints, ligaments, and tendons, serves as the foundation for maintaining human posture, mobility, and overall biomechanical functionality. However, with ageing, chronic overuse, and acute injuries, conditions such as osteoarthritis, intervertebral disc degeneration, muscle atrophy, and ligament or tendon tears have become increasingly prevalent and pose serious clinical challenges. These disorders not only result in pain, functional loss, and a marked reduction in patients’ quality of life but also impose substantial social and economic burdens. Current treatment modalities, including surgical intervention, pharmacotherapy, and physical rehabilitation, often do not effectively restore the functionality of damaged tissues and are associated with high recurrence rates and long–term complications, highlighting significant limitations in their efficacy. Thus, there is a strong demand to develop novel and more effective therapeutic and reparative strategies. Organoid technology, as a three–dimensional micro–tissue model, can replicate the structural and functional properties of native tissues in vitro, providing a novel platform for in–depth studies of disease mechanisms, optimisation of drug screening, and promotion of tissue regeneration. In recent years, substantial advancements have been made in the research of bone, muscle, and joint organoids, demonstrating their broad application potential in personalised and regenerative medicine. Nonetheless, a comprehensive review of current research on skeletal organoids is still lacking. Therefore, this article aims to present an overview of the definition and technological foundation of organoids, systematically summarise the progress in the construction and application of skeletal organoids, and explore future opportunities and challenges in this field, offering valuable insights and references for researchers.

    Jun Li, Honghao Hou, Qian Li, Junjie Liu, Yunlong Zhao, Chaoran Zhao, Zhentao Li, Leyu Wang, Xiaozhong Qiu
    2024, 5(4):  411-424.  doi:10.12336/biomatertransl.2024.04.006
    Cardiac organ chip is an advanced bioengineering and microfluidic device that aims to simulate the physiological functions and pathological states of the heart. It provides an in vitro model for cardiac disease research and improves the efficiency and accuracy of drug development and toxicology testing, which is expected to play a significant role in healthcare.
    Abstract ( 24 )   HTML ( 8)   PDF (4112KB) ( 11 )  
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    Cardiovascular diseases are a leading cause of death worldwide, and effective treatment for cardiac disease has been a research focal point. Although the development of new drugs and strategies has never ceased, the existing drug development process relies primarily on rodent models such as mice, which have significant shortcomings in predicting human responses. Therefore, human–based in vitro cardiac tissue models are considered to simulate physiological and functional characteristics more effectively, advancing disease treatment and drug development. The microfluidic device simulates the physiological functions and pathological states of the human heart by culture, thereby reducing the need for animal experimentation and enhancing the efficiency and accuracy of the research. The basic framework of cardiac chips typically includes multiple functional units, effectively simulating different parts of the heart and allowing the observation of cardiac cell growth and responses under various drug treatments and disease conditions. To date, cardiac chips have demonstrated significant application value in drug development, toxicology testing, and the construction of cardiac disease models; they not only accelerate drug screening but also provide a new research platform for understanding cardiac diseases. In the future, with advancements in functionality, integration, and personalised medicine, cardiac chips will further simulate multiorgan systems, becoming vital tools for disease modelling and precision medicine. Here, we emphasised the development history of cardiac organ chips, highlighted the material selection and construction strategy of cardiac organ chip electrodes and hydrogels, introduced the current application scenarios of cardiac organ chips, and discussed the development opportunities and prospects for their of biomedical applications.

    Jingtao Huang, Aikang Li, Rongji Liang, Xiaohao Wu, Shicheng Jia, Jiayou Chen, Zilu Jiao, Canfeng Li, Xintao Zhang, Jianjing Lin
    2024, 5(4):  425-443.  doi:10.12336/biomatertransl.2024.04.007
    We reviews the use of stem cells and biomaterials to assemble bone and cartilage organoids and for the treatment of bone and cartilage diseases, providing insights into tissue regeneration therapeutic strategies. This review highlights the potential of these organoids to advance regenerative medicine.
    Abstract ( 62 )   HTML ( 18)   PDF (1867KB) ( 37 )  
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    Bone and cartilage tissues are essential for movement and structure, yet diseases like osteoarthritis affect millions. Traditional therapies have limitations, necessitating innovative approaches. Organoid technology, leveraging stem cells’ regenerative potential, offers a novel platform for disease modelling and therapy. This review focuses on advancements in bone/cartilage organoid technology, highlighting the role of stem cells, biomaterials, and external factors in organoid development. We discuss the implications of these organoids for regenerative medicine, disease research, and personalised treatment strategies, presenting organoids as a promising avenue for enhancing cartilage repair and bone regeneration. Bone/cartilage organoids will play a greater role in the treatment of bone/cartilage diseases in the future, and promote the progress of biological tissue engineering.

    COMMENTARY
    A novel strategy for treating acute liver failure: encapsulated proliferating human hepatocyte organoids
    Xiangying Meng, Aihui Liu, Oulayvanh Phangthavong, Yi Sun
    2024, 5(4):  444-446.  doi:10.12336/biomatertransl.2024.04.008
    Abstract ( 32 )   HTML ( 10)   PDF (1516KB) ( 16 )  
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    Human cartilage organoids and beyond
    Kai Dai, Jing Wang
    2024, 5(4):  447-450.  doi:10.12336/biomatertransl.2024.04.009
    Abstract ( 23 )   HTML ( 8)   PDF (672KB) ( 17 )  
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    Human foetal brain self-organises into long-term expanding organoids
    Zhu A. Z. Zheng, Wei Wang, Fu M. Yang, Wei Q. Liu, Guo S. Han
    2024, 5(4):  451-453.  doi:10.12336/biomatertransl.2024.04.010
    Abstract ( 27 )   HTML ( 7)   PDF (697KB) ( 23 )  
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    Farnesoid X receptor: a potential key target for maintaining liver organoid growth
    Haoran Bai, Guanzhong Wu, Yiqing Shi, Zhipeng Han
    2024, 5(4):  454-456.  doi:10.12336/biomatertransl.2024.04.011
    Abstract ( 16 )   HTML ( 6)   PDF (269KB) ( 9 )  
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