ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomaterials
This article is part of the Research TopicBiodegradable Polymers for Biomedical Applications - Volume IVView all 7 articles
Polyethylene glycol-Polyester Based Temperature-Sensitive Hydrogel Delivering Mesenchymal Stem Cell-Derived Exosomes Enhances Acute Skin Wound Healing
Provisionally accepted
- 1University of Science and Technology of China, Hefei, China
- 2Northeastern University, Shenyang, China
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Skin wound healing remains a significant clinical challenge. Conventional dressings have limitations in maintaining an optimal wound microenvironment and preventing secondary injury. In this study, we developed a Poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA, PPP) thermosensitive hydrogel loaded with mesenchymal stem cell-derived exosomes (MSC-Exos) to enhance acute skin wound healing by prolonging exosome retention and bioavailability at the wound site. The hydrogel exhibited a rapid sol-gel transition at approximately 32 °C, demonstrating good mechanical stability (storage modulus (G') > loss modulus (G")) and self-healing properties at physiological temperature. In vitro experiments revealed that PPP/Exos showed superior biocompatibility with L929 mouse fibroblast cells (L929 cells) and human umbilical vein endothelial cells (HUVECs), significantly promoting cell proliferation and vascular tube formation. In a Sprague-Dawley (SD) rat full-thickness skin defect model, the PPP/Exos group markedly accelerated wound closure. By day 14, wound closure reached 98.6% in the PPP/Exos group, compared with 87.6% in the control group. Histopathological examination further revealed that PPP/Exos treatment effectively enhanced granulation tissue formation, attenuated inflammatory responses, facilitated re-epithelialization, and substantially increased collagen deposition. Through immunohistochemical analysis, we identified three mechanisms underlying the enhanced wound healing: promoted angiogenesis, accelerated myofibroblast differentiation, and reduced inflammation. Collectively, the PPP/Exos thermosensitive hydrogel, with its excellent biocompatibility, injectability, and sustained exosome release characteristics, significantly promotes wound healing through synergistic "angiogenesis-tissue remodeling-anti-inflammation" effects. This system offers a promising therapeutic strategy for clinical wound management and establishes a solid foundation for applications in regenerative medicine.
Keywords: Wound Healing, PLGA-PEG-PLGA, Thermosensitive hydrogel, Mesenchymalstem cells, Exosomes
Received: 23 Oct 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Wei, Ren, Hu and Wei. 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:
Jianshe Hu, hujs@mail.neu.edu.cn
Haiming Wei, ustcwhm@ustc.edu.cn
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