AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Burns & Trauma Article
PDF (3.1 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Multiple dynamic crosslinked multifunctional hydrogels with glucose/pH dual-responsive adipose-derived stem cells-exosomes-releasing for diabetic wound healing

Yue Zhang1,‡ , Meng Li2,‡, Shijie Song1,‡, Fenghui Hei1, Shaoyang Ma2, Jiao Cao2, Baolin Guo2( ), Dahai Hu1 ( )
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi’an, Shaanxi 710032, China
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, and State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi’an Jiaotong University, Hedi Road, Chang’an District, Xi’an, Shaanxi 710049, China

‡Yue Zhang, Meng Li and Shijie Song contributed equally to this work.

Show Author Information

Highlights

• We propose a glucose/pH dual-responsive adipose-derived stem cells exosome (ADSC-exo)-releasing hydrogel therapy and provide a potential mechanism for alleviating the inflammatory response in diabetic wounds.

• We successfully developed a smart hydrogel delivery system that responds to the high glucose and acidic microenvironments, enabling controlled release of ADSC-exos under pathological conditions.

• The hydrogel reduced the release of inflammatory cytokines and alleviated the inflammatory response via the Notch/NF-κB/NLRP3 signaling pathway.

Abstract

Background

Diabetic wounds feature a high-glucose and acidic microenvironment that impairs macrophage polarization and healing. Adipose-derived stem cell-derived exosomes (ADSC-exos) show therapeutic potential but suffer from rapid clearance. This study aimed to develop a smart hydrogel for glucose/pH-responsive ADSC-exos release.

Methods

A dual-responsive hydrogel (HAP/OCS/PEG/Ag-E) was fabricated via dynamic triple cross-linking. Characterization included rheometry, mechanical tests, and microscopy. In vitro macrophage polarization was assessed via flow cytometry and Western blot. A diabetic mouse wound model evaluated healing rates, histology, angiogenesis, and inflammation. Proteomics and pathway inhibition studies explored mechanisms. Statistical analysis used t-tests and ANOVA.

Results

The hydrogel exhibited excellent self-healing, adhesion, and controlled ADSC-exos release under high-glucose/acidic conditions. It promoted M2 macrophage polarization, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and accelerated wound healing with enhanced angiogenesis and collagen deposition. Mechanistically, the hydrogel suppressed the Notch/NF-κB/NLRP3 signaling pathway.

Conclusion

The smart hydrogel facilitates diabetic wound healing through microenvironment-responsive ADSC-exos release and Notch/NF-κB/NLRP3 pathway inhibition, offering a promising strategy for chronic wound treatment.

Keywords

Glucose/pH dual responsive hydrogelsADSC-exosMacrophageChronic diabetic woundInflammation

References

【1】
【1】
 
 
Crossref Google Scholar
Burns & Trauma
Volume 13 Issue 12,
December 2025
Article number: tkaf059
DOI: 10.1093/burnst/tkaf059

{{item.num}}

Comments on this article

Go to comment

< Back to all reports

Review Status: {{reviewData.commendedNum}} Commended , {{reviewData.revisionRequiredNum}} Revision Required , {{reviewData.notCommendedNum}} Not Commended Under Peer Review

Review Comment

Cite this Report
Close
Close
Cite this article:
Zhang Y, Li M, Song S, et al. Multiple dynamic crosslinked multifunctional hydrogels with glucose/pH dual-responsive adipose-derived stem cells-exosomes-releasing for diabetic wound healing. Burns & Trauma, 2025, 13(12): tkaf059. https://doi.org/10.1093/burnst/tkaf059

2

Views

0

Downloads

0

Crossref

0

Web of Science

6

Scopus
Received: 17 March 2025
Revised: 24 August 2025
Accepted: 25 August 2025
Published: 14 October 2025
© The Author(s) 2025. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.