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REVIEW ARTICLE

Advancing tumor organoid 3D culture with functionalized hydrogels: Applications in precision medicine and technological challenges

Guangshun Zeng1† ,  Jiayi Niu1† ,  Jinqi Wang1 ,  Lulin Qiao2 ,  Na Tang3 ,  Mingzhu Zhang4* ,  Fushan Hou4*
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1 Shanxi Medical University, Taiyuan, Shanxi, China
2 Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
3 Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
4 Department of Foot and Ankle Surgery, Beijing Tongren Hospital of Capital Medical University, Beijing, China
†These authors contributed equally to this work.
OR, 026050007 https://doi.org/10.36922/OR026050007
Received: 29 January 2026 | Revised: 18 March 2026 | Accepted: 18 March 2026 | Published online: 5 June 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

Traditional tumor models are limited by short in vitro survival, pronounced interspecies differences, and inadequate recapitulation of tumor heterogeneity. This review systematically classifies hydrogels into matrix-supporting, signal-regulating, and stimulus-responsive categories based on functional characteristics, and summarizes the fabrication strategies of natural, synthetic, and composite hydrogels. Tumor organoids preserve the genotype and phenotype of primary tumors; their integration with hydrogels provides complementary advantages, enabling the reconstruction of biomimetic tumor microenvironments, long-term in vitro culture, and personalized tumor modeling. Hydrogel-tumor organoid systems therefore demonstrate substantial value in tumor model development, high-throughput drug screening, and the investigation of drug resistance mechanisms. However, several challenges remain, including insufficient matching of mechanical properties, batch-to-batch variability of hydrogels, stringent organoid culture requirements, and the lack of standardized protocols—among which the standardization of natural hydrogels represents a major barrier to clinical translation. Finally, this review highlights emerging technological directions, including intelligent hydrogels and 3D bioprinting, outlines trends in interdisciplinary integration, and discusses future clinical application prospects. Addressing issues related to standardization and cost will be critical for fully unlocking the potential of hydrogel–organoid platforms in precision oncology.

Graphical abstract
Keywords
Hydrogels
Tumor organoids
Tumor models
Precision medicine
Funding
This work was funded by the General Program of Natural Science Foundation of Shanxi Province, China (Grant No. 202203021211030) and the Shanxi Provincial Administration of Traditional Chinese Medicine Program (Grant No. 2023ZYYC2037). The authors gratefully acknowledge the support provided by these funding agencies.
Conflict of interest
The authors declare that they have no conflict of interest.
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