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REVIEW ARTICLE
Organoids: Applications and challenges of advanced

hydrogels in tissue systems

Yuxin Jin 1† , Qizhu Chen 2† , Longhui Gong 1 , Xinfeng Zheng 2 , Linjie Chen 1 , Bo Li 2 , Hao Zhou 3 ,
Kenny Yat Hong Kwan , Ouqiang Wu 1 , Zitian Zheng 5 , Morgan Jones , Yuting Huang ,
4
7
6
Dilhana S. Badurdeen , Yikun Chen 1 , Kai Chen *, Sunren Sheng * , Shengdan Jiang * , and Aimin Wu *
2
1
1
7
8
1 Department of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics
of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang,
China
2 Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
3 Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
4 Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
5 Department of Sports Medicine, Peking University Third Hospital Institute of Sports Medicine of Peking University, Beijing, China
6 Spine Unit, The Royal Orthopaedic Hospital, Bristol Road South, Northfield, Birmingham B31 2AP, United Kingdom
7 Division of Gastroenterology & Hepatology, Mayo Clinic, Florida, United States of America
8 School of Biomedical Sciences, The University of Western Australia, Perth, Australia
† These authors contributed equally to this work.
*Corresponding authors: Aimin Wu (aiminwu@wmu.edu.cn); Shengdan Jiang (jiangshengdan@xinhuamed.com.cn); Sunren Sheng
(shengsunren@wmu.edu.cn); Kai Chen (kai.chen@uwa.edu.au)

Citation: Jin Y, Chen Q, Gong L, Abstract
et al. Organoids: Applications and
challenges of advanced hydrogels Repair and regeneration of tissues and organs remain central to medical research.
in tissue systems. Organoid Res.
2025;1(2):8262. Organoids, advanced models created through in vitro tissue engineering, enable stem
doi: 10.36922/or.8262 cells to form three-dimensional structures that replicate organ tissues and function
Received: September 10, 2024 spontaneously. The advancement of organoid technology has greatly enhanced
Revised: October 18, 2024 our understanding of disease progression and organ development. A crucial
component of this technology is the development of appropriate scaffolds to
Accepted: November 17, 2024 support organoid growth. Recently, hydrogels have emerged as promising materials
Published online: April 16, 2025 due to their excellent biocompatibility, tunability, and degradability, facilitating
Copyright: © 2025 Author(s). This the in vitro culture of stem cells and their differentiation into various organoids.
is an Open-Access article distributed However, more complex organ models, which involve extensive intercellular and
under the terms of the Creative extracellular communication, present significant challenges for present research.
Commons Attribution License,
permitting distribution, and reproduction Moreover, advancements in biomaterial fabrication and their integration with
in any medium, which provided that the organoid technology remain underexplored. This review explores the pivotal role
original work is properly cited. of hydrogels in organoid preparation, comparing the advantages and limitations of
Publisher’s Note: AccScience different hydrogel fabrication methods. It also highlights recent advancements in the
Publishing remains neutral with regard application of organoid hydrogels across various biological systems and discusses
to jurisdictional claims in published future challenges and directions in this field.
maps and institutional affiliations.

Keywords: Organoids; Stem cells; Tissue regeneration; Hydrogels

1. Introduction and treatment guidelines are typically based on experimental
efficacy. However, 2D models possess limitations for studying
Traditional two-dimensional (2D) cell culture models have complex organs such as the heart and brain due to their
greatly enhanced our understanding of diseases involving simplistic cellular layers and lack of structural complexity,
simple cellular structures and contributed to research in signal which oftentimes are the factors keeping cells isolated from
transduction pathways and drug delivery. Clinical drug design their native contexts, disrupting intercellular communication
1
Volume 1 Issue 2 (2025) 1 doi: 10.36922/or.8262