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REVIEW
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Hydrogel-based biomaterials for brain regeneration after stroke: gap to clinical translation

Hanlai Li1 ,  Tingting Gu1 ,  Jingjing Xu1 ,  Lin Gan1 ,  Chang Liu2 ,  Jixian Wan3 ,  Zhihao Mu4 ,  Haiyan Lyu5 ,  Zhibin Wang6 ,  Qianqian Liu7 ,  Jie Chen8 ,  Yaohui Tang1*
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1 School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
2 Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
3 Department of Rehabilitation Medicine, Ruijin Hospital, School of Medicine, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
4 Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunan Province, China
5 Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
6 Lingyi iTECH Manufacturing Co., Ltd., Suzhou, Jiangsu Province, China
7 Ankerui (Shanxi) Biological Cell Co., Ltd., Taiyuan, Shanxi Province; 8Jiangsu Charity Biotech Co., Ltd., Shanghai, China
BMT 2025 , 6(2), 165–180; https://doi.org/10.12336/bmt.24.00020
Submitted: 11 April 2024 | Revised: 20 September 2024 | Accepted: 21 October 2024 | Published: 25 June 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Due to the limited effects of current treatments on brain repair and regeneration, stroke continues to be the predominant cause of death and long-term disability on a global scale. In recent years, hydrogel-based biomaterials combined with stem cells and extracellular vesicles have emerged as promising new treatments to improve brain regeneration after stroke. However, the clinical translation of hydrogel-based biomaterials for the treatment of brain injury is still far from satisfactory. In this review, we first summarise the present status of stroke-related clinical treatments and the advantages provided by hydrogel-based materials in combination with stem cells and extracellular vesicles in preclinical studies. We then focus on the possible causes of the gap between preclinical studies and clinical translation of hydrogel-based biomaterials from the perspective of biocompatibility and safety, the choices of preclinical models, the lack of clinical noninvasive imaging methods, standardisation and quality control, manufacturing scalability, and regulatory compliance. With the progress in the abovementioned areas, we believe that the clinical translation of hydrogel-based biomaterials will greatly improve brain regeneration after stroke and that this improvement will be realised by the general public in the near future.

Keywords
Biomaterials
Clinical translation
Hydrogel
Stroke
Funding
This work was supported by grants from the National Key R&D Program of China, No. 2019YFA0112000 (to YT); the National Natural Science Foundation of China (NSFC), Nos. 82071284 (to YT), 82371307 (to YT), 82172529 (to JW), 32060184 (to HM); Natural Science Foundation of Shanghai, No. 21ZR1451700 (to HL); Young Leading Scientists Cultivation Plan supported by Shanghai Municipal Education Commission, No. ZXWH1082101 (to YT); Interdisciplinary Program of Shanghai Jiao Tong University, No. ZH2018QNA16 (to YT); Key Projects of the National Center for Translational Medicine SUITM-202306 (to YT); and Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University, No. 202101AY070001-044 (to HM).
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Conflict of interest
Zhibin Wang, Qianqian Liu, and Jie Chen are employees of Lingyi iTECH Manufacturing Co., Ltd., Ankerui (Shanxi) Biological Cell Co., Ltd., and Jiangsu Charity Biotech Co., Ltd., respectively. There is no conflict of interest for this review.
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