Hong Yang, Li Ruiyang, Sheng Shihao, Zhou Fengjin, Bai Long, Su Jiacan
Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
MedEng-X Institutes, Shanghai University, Shanghai, 200444, China.
J Orthop Translat. 2025 Jul 3;53:260-273. doi: 10.1016/j.jot.2025.06.011. eCollection 2025 Jul.
Organoids, generated through three-dimensional in vitro culture, are cellular aggregates that accurately mimic the complex microenvironment, cell-cell interactions, and signaling mechanisms of native tissues. These models offer transformative advantages in studying disease mechanisms, drug screening, and personalized medicine. Compared to traditional two-dimensional cell cultures and animal models, organoid systems exhibit higher physiological relevance, effectively mitigating species-specific discrepancies while significantly enhancing clinical translational feasibility. However, current organoid research primarily focuses on soft tissues such as the heart, liver, spleen, lungs, and kidneys, with limited progress in hard tissue organoids, particularly bone organoids. Given the pivotal role of bone tissue in clinical bone repair, disease mechanism elucidation, and drug screening, this field demands further investigation. Based on our previous research, this review introduces a five-stage iterative framework for bone organoid development: 1.0 (physiological model), 2.0 (pathological model), 3.0 (structural model), 4.0 (composite model), and 5.0 (applied model). This paper systematically reviews the technical pathways for bone organoid construction, highlights the core features and scientific value of each model iteration, and explores the current challenges and future directions in this emerging field. The goal is to provide theoretical and technological insights that advance bone organoid research, offering innovative solutions for bone-related disease studies and clinical applications. The translational potential of this article: This review provides a systematic overview of bone organoid development, highlighting their remarkable role in orthopaedic research and in clinical practice. Through the incorporation of advanced technologies like artificial intelligence and 3D bioprinting, bone organoids provide novel approaches to the development of regenerative medicine and customized orthopaedic treatments.
类器官是通过三维体外培养生成的细胞聚集体,能够精确模拟天然组织的复杂微环境、细胞间相互作用和信号传导机制。这些模型在研究疾病机制、药物筛选和个性化医疗方面具有变革性优势。与传统的二维细胞培养和动物模型相比,类器官系统具有更高的生理相关性,有效减少了物种特异性差异,同时显著提高了临床转化可行性。然而,目前的类器官研究主要集中在心脏、肝脏、脾脏、肺和肾脏等软组织,硬组织类器官,尤其是骨类器官的进展有限。鉴于骨组织在临床骨修复、疾病机制阐明和药物筛选中的关键作用,该领域需要进一步研究。基于我们之前的研究,本综述介绍了骨类器官发育的五阶段迭代框架:1.0(生理模型)、2.0(病理模型)、3.0(结构模型)、4.0(复合模型)和5.0(应用模型)。本文系统回顾了骨类器官构建的技术途径,突出了每个模型迭代的核心特征和科学价值,并探讨了这一新兴领域当前面临的挑战和未来方向。目标是提供推进骨类器官研究的理论和技术见解,为骨相关疾病研究和临床应用提供创新解决方案。本文的转化潜力:本综述系统概述了骨类器官的发展,突出了它们在骨科研究和临床实践中的显著作用。通过整合人工智能和3D生物打印等先进技术,骨类器官为再生医学和定制骨科治疗的发展提供了新方法。
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