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Review | Open Access

Engineering the organoid microenvironment: Applications of hydrogel matrices in organoid culture

Yaxiao Li1,2,3,Wenhsuan Chou1,Weiwei Zhang1,4Yi Wang1,5,7,8 ( )Chong Zhang1,5,6,7,8( )
Department of Chemical Engineering, Tsinghua University, Beijing 100084, China
Logistics University of Chinese People’s Armed Police Forces, Tianjin 300309, China
Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin 300309, China
Department of Clinical Pharmacy, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China
Ministry of Education Key Laboratory for Industrial Biocatalysis, Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China
Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China
State Key Laboratory of Green Biomanufacturing, Beijing 100084, China
Beijing Key Laboratory of Recombinant Proteins and Biomanufacturing, Beijing 100084, China

These authors contributed equally to this work.

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Abstract

Organoids, which recapitulate human organ structure and function, have been widely used in disease modeling, drug discovery, personalized medicine, and regenerative therapy, demonstrating strong potential for future biomedical applications. Successful organoid culture (OC) depends on a matrix that provides mechanical support and in vivo microenvironment mimicry, both essential for cellular adhesion, proliferation, and differentiation. Owing to their tunable stiffness and viscoelasticity, which enable adaptation to diverse OCs, hydrogels have become key materials in OC matrix development. This review summarizes current advances in hydrogel systems, encompassing naturally derived and synthetic hydrogels used in OC, with an emphasis on their composition and physicochemical properties. This study aims to provide guidance for hydrogel selection in organoid research. This study further explores how hydrogel composition governs gelation behavior and ultimately influences organoid growth and functionality, providing insights for the future engineering of “all-purpose” hydrogel matrices.

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Health Engineering
Article number: 9460013

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Cite this article:
Li Y, Chou W, Zhang W, et al. Engineering the organoid microenvironment: Applications of hydrogel matrices in organoid culture. Health Engineering, 2026, 2: 9460013. https://doi.org/10.26599/HE.2026.9460013

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Received: 04 November 2025
Revised: 13 December 2025
Accepted: 25 December 2025
Published: 14 August 2026
© The Author(s) 2026. 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/)