ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomaterials
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1688905
This article is part of the Research TopicThe Application of Novel Biomaterials and Emerging Techniques in Musculoskeletal DisordersView all 7 articles
pH-Responsive Hydrogel System Loaded with Curcumin-Preconditioned Mesenchymal Stem Cell Exosomes for Enhanced Diabetic Wound Healing in Orthopedic Applications
Provisionally accepted
- 1Guizhou Provincial People's Hospital, Guiyang, China
- 2Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Wounds, a major complication in orthopedic-related diseases, present significant challenges for orthopedic surgeons due to impaired healing driven by vascular dysfunction, oxidative stress, and chronic inflammation. This study introduces an injectable, self-healing, pH-responsive hydrogel system delivering curcumin-preconditioned mesenchymal stem cell (MSC)-derived exosomes (Cur-Exo) to enhance diabetic wound repair, offering a cell-free therapeutic strategy with applications in orthopedic regenerative medicine.The hydrogel, formed through dynamic cross-linking of amphoteric chitosan and multi-armed polyethylene glycol, exhibits antibacterial properties and degrades selectively in the acidic microenvironment (pH 4.5–6.5) of diabetic wounds. Loaded with Cur-Exo, it enables controlled release of bioactive molecules, leveraging the enhanced antioxidant, anti-inflammatory, and pro-angiogenic properties of exosomes from curcumin-preconditioned MSCs. In vitro, Cur-Exo@Gel exhibited excellent biocompatibility, promoted endothelial cell migration, and enhanced angiogenesis, while reducing oxidative stress. It also modulated macrophage polarization by decreasing pro-inflammatory M1 markers (iNOS) via upregulation of Iκβα and reduced p65 phosphorylation, fostering an anti-inflammatory microenvironment. The hydrogel's inherent antibacterial properties (>50% reduction in E. coli and S. aureus, p< 0.05) further mitigate infection risks critical in orthopedic wounds. In vivo, using a diabetic rat full-thickness skin defect model, Cur-Exo@Gel significantly reduced wound areas, with enhanced epithelial migration and collagen deposition. These findings highlight Cur-Exo@Gel as a promising cell-free therapeutic strategy for accelerating chronic orthopedic wound repair, offering novel insights for regenerative orthopedics.
Keywords: pH-responsive, Curcumin, anti-bacterial, Oxidative Stress, Immune homeostasis
Received: 19 Aug 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Ding, Li, Li, Chen, Guo and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qiuyue Ding, martinqiu023@163.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.