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Review | Open Access | Just Accepted

Engineering the Organoid Microenvironment: The Application of Hydrogel Matrics in Organoid Culture

Yaxiao LI1,2,3,*Wenhsuan CHOU1,*Weiwei ZHANG1,4Yi WANG1,5,7,8 ( )Chong ZHANG1,5,6,7,8( )

1 Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.

2 Logistics University of Chinese People’s Armed Police Forces, Tianjin 300309, China.

3 Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin 300309, China.

4 Department of Clinical Pharmacy, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China.

5 Ministry of Education Key Laboratory for Industrial Biocatalysis, Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China.

6 Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China.

7 State Key Laboratory of Green Biomanufacturing,China.

8 Beijing Key Laboratory of Recombinant Proteins and Biomanufaturing, China.

* These authors contributed equally to this work.

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Abstract

Organoids, which recapitulate the structure and function of human organs, have been widely used in various fields including disease modeling, drug discovery, personalized medicine, and regenerative therapy, demonstrating significant potential for future biomedical applications. Successful organoid culture depends on a matrix with the dual capability of mechanical support and mimicry of the in vivo microenvironment, both essential for cellular adhesion, proliferation, and differentiation. Owing to their tunable stiffness and viscoelasticity, which enable adaptation to the culture of different organoids, hydrogels have become a key material in the development of organoid culture matrices. This review summarizes current advances in hydrogels systems, encompassing both naturally derived and synthetic hydrogels used in organoid culture, with emphasis on their composition and physicochemical properties, with the aim of assisting researchers in selecting suitable hydrogels for their studies. We further explore how hydrogels composition governs gelation behavior and, ultimately, influences organoid growth and functionality, providing insights for the future development of "all-purpose" hydrogel matrices.

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Cite this article:
LI Y, CHOU W, ZHANG W, et al. Engineering the Organoid Microenvironment: The Application of Hydrogel Matrics in Organoid Culture. Health Engineering, 2025, https://doi.org/10.26599/HE.2026.9460013

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Received: 04 November 2025
Revised: 13 December 2025
Accepted: 25 December 2025
Available online: 29 December 2025

© The Author(s) 2025. Published by Tsinghua University Press.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the original author(s) and the source, a link to the license is provided, and any changes made are indicated. See (https://creativecommons.org/licenses/by/4.0/)