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Review
. 2024 Nov 15;5(4):390-410.
doi: 10.12336/biomatertransl.2024.04.005. eCollection 2024.

Skeletal organoids

Chen Zhang  1   2   3 , Yingying Jing  1   2 , Jianhua Wang  4 , Zhidao Xia  5 , Yuxiao Lai  6 , Long Bai  1   2   7 , Jiacan Su  1   2   4
Affiliations
Review

Skeletal organoids

Chen Zhang et al. Biomater Transl. .

Abstract

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.

Keywords: applications; construction strategies; organoids; skeletal system.

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Conflict of interest statement

Conflicts of interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.. Skeletal system composition and diseases. Created with BioRender.com. DMD: Duchenne muscular dystrophy.
Figure 2.
Figure 2.. Comparison across multiple systems. Created with BioRender.com. 2D: two-dimensional; AA: amino acid; BMPs: bone morphogenetic proteins; EGF: epidermal growth factor; ESCs: embryonic stem cells; FGF: fibroblast growth factor; IGF: insulin-like growth factor; iPSCs: induced pluripotent stem cells.
Figure 3.
Figure 3.. Development of skeletal organoids. Created with BioRender.com. ECM: extracellular matrix; hESCs: human embryonic stem cells; hPSCs: human pluripotent stem cells; iPSCs: induced pluripotent stem cells; mESCs: mouse embryonic stem cells.
Figure 4.
Figure 4.. Construction and application of bone organoids. Created with BioRender.com. BMPs: bone morphogenetic proteins; FGF: fibroblast growth factor; hBMCs: human bone stem cells; iPSCs: induced pluripotent stem cells; MSCs: mesenchymal stem cells; OBs: osteoblasts; PEG: polyethylene glycol.
Figure 5.
Figure 5.. Construction and application of muscle organoids. Created with BioRender.com. BMP: bone morphogenetic proteins; FGF: fibroblast growth factor; hPSCs: human pluripotent stem cells; iPSCs: induced pluripotent stem cells; MPCs: muscle progenitor cells; SCs: satellite cells.
Figure 6.
Figure 6.. Construction and application of joint organoids. Created with BioRender.com. BMP: bone morphogenetic protein; BMSCs: bone mesenchymal stem cells; dECM: decellularised extracellular matrix; iPSCs: induced pluripotent stem cells; MSCs: mesenchymal stem cells; TGF-β: transforming growth factor-β.
Figure 7.
Figure 7.. Construction and application of ligament and tendon organoids. Created with BioRender.com. ADSCs: adipose-derived stem cells; BMCs: bone marrow cells; FGF: fibroblast growth factor; LDSCs: lipoma-derived stem cells; PLA: polylactic acid; TDSCs: tendon‐derived stem cells; TGF-β: transforming growth factor-β.
Figure 8.
Figure 8.. Applications of skeletal organoids. Created with BioRender.com.
See this image and copyright information in PMC

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