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REVIEW ARTICLE

Hydrogel microsphere-mediated treatment of intervertebral disc degeneration and organoid construction

Jiyuan Hong1† ,  Zitao Zeng1† ,  Weiliang Cui1 ,  Ruoyu Cheng2,3,4* ,  Zhong Liao1* ,  Wei Chen1*
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1 Department of Orthopaedics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
2 Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
3 Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
4 Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
†These authors contributed equally to this work.
OR, 026090012 https://doi.org/10.36922/OR026090012
Received: 27 February 2026 | Revised: 7 April 2026 | Accepted: 10 April 2026 | Published online: 15 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Intervertebral disc degeneration is a complex pathological process driven by multiple factors, involving cellular pathological changes, an imbalance in the inflammatory microenvironment, and oxidative stress mechanisms, and significantly impacts patients’ quality of life. Current treatments lack therapeutic strategies targeting tissue regeneration and repair. With excellent biocompatibility, injectability, tunable mechanical properties, and smart responsive capabilities, hydrogel microspheres serve as ideal carriers for drug, gene, and cell therapies in intervertebral disc degeneration. This paper systematically reviews the preparation techniques and properties of hydrogel microspheres, focusing on their key mechanisms and advantages in gene delivery, drug delivery, and cell-scaffold applications. Subsequently, it summarizes cutting-edge advances in the construction of disc organoids, highlighting the advantages of hydrogel microspheres in mimicking extracellular matrices, constructing 3D biomimetic microenvironments, supporting cell proliferation and differentiation, and recapitulating degenerative microenvironments, thus providing a new platform for disease modeling and personalized therapy. Finally, future directions for hydrogel microsphere-based therapies for disc degeneration are envisioned, including multimodal smart-response design, personalized manufacturing, integrated organoid applications, and non-invasive, precise delivery technologies. This review aims to advance the management of disc degeneration from symptom relief toward functional restoration, thereby promoting clinical translation and the development of precision regenerative medicine.

Graphical abstract
Keywords
Organoids
Hydrogel microspheres
Intervertebral disc degeneration
Gene therapy
Drug therapy
Cell therapy
Funding
This work was supported by the National Natural Science Foundation of China (No. 82502869), the Investigator Initiation Fund Project of Fujian Medical University Union Hospital (No. 2023XH010), the Joint Funds for the innovation of Science and Technology, Fujian province (No. 2024Y9305), and the Fujian Provincial Natural Science Foundation of China (No. 2025J08185).
Conflict of interest
The authors declare they have no competing interests.
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