Hydrogel-based delivery of extracellular vesicles for skin wound healing: design strategies, therapeutic mechanisms, and translational perspectives
- 1Department of Medical Cosmetology, Hospital of Chengdu University of Traditional Chinese Medicine , ,
- 2State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , ,
Abstract
Skin wound healing remains a formidable clinical challenge. Extracellular vesicles (EVs) have attracted considerable attention as therapeutic candidates for wound repair, given their intrinsic capacities to modulate inflammation, promote angiogenesis, and stimulate tissue regeneration. Hydrogels, with favorable biocompatibility, tunable degradation, and sustained-release properties, serve as candidate EV delivery platforms. This review critically examines the landscape of hydrogel-mediated EV delivery for skin wound repair, progressing from EV sources and engineering strategies, through hydrogel design principles and crosslinking modalities, to the modes of EV-hydrogel integration and the multi-dimensional mechanisms including immunomodulation, angiogenesis, extracellular matrix remodeling, and cell proliferation that drive the healing process. Recent advances across acute, diabetic chronic, and burn wounds are evaluated, together with stimuli-responsive hydrogels capable of sensing wound microenvironmental cues such as reactive oxygen species, pH, and matrix metalloproteinase activity to enable microenvironment-responsive EV release, representing a transition from passive delivery toward more adaptive and controlled therapeutic strategies. Nevertheless, the current evidence is derived predominantly from in vitro and small-animal studies and is constrained by heterogeneous EV preparations, insufficient standardization of manufacturing and quality control, and limited clinical validation. Finally, critical challenges including production standardization, scalable manufacturing, and regulatory barriers to clinical translation are analyzed, and future directions for advancing hydrogel-EV systems toward clinical translation are discussed, aiming to provide insights and perspectives for further fundamental research and clinical translation of hydrogel-EV systems in skin wound healing.
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BibTeX
@article{jin2026hydrogelbased,
title = {{Hydrogel-based delivery of extracellular vesicles for skin wound healing: design strategies, therapeutic mechanisms, and translational perspectives}},
author = {Yuqiu Jin and Jun Lu and Jingping Wu and Yi Zuo and Huilan Zheng and Fengrui Cheng},
journal = {Frontiers in bioengineering and biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1976532},
url = {https://europepmc.org/article/PMC/PMC13720249},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hydrogel-based delivery of extracellular vesicles for skin wound healing: design strategies, therapeutic mechanisms, and translational perspectives
AU - Yuqiu Jin
AU - Jun Lu
AU - Jingping Wu
AU - Yi Zuo
AU - Huilan Zheng
AU - Fengrui Cheng
PY - 2026
DA - 2026/10/16
JO - Frontiers in bioengineering and biotechnology
DO - 10.3389/fbioe.2026.1976532
UR - https://europepmc.org/article/PMC/PMC13720249
AB - Skin wound healing remains a formidable clinical challenge. Extracellular vesicles (EVs) have attracted considerable attention as therapeutic candidates for wound repair, given their intrinsic capacities to modulate inflammation, promote angiogenesis, and stimulate tissue regeneration. Hydrogels, with favorable biocompatibility, tunable degradation, and sustained-release properties, serve as candidate EV delivery platforms. This review critically examines the landscape of hydrogel-mediated EV delivery for skin wound repair, progressing from EV sources and engineering strategies, through hydrogel design principles and crosslinking modalities, to the modes of EV-hydrogel integration and the multi-dimensional mechanisms including immunomodulation, angiogenesis, extracellular matrix remodeling, and cell proliferation that drive the healing process. Recent advances across acute, diabetic chronic, and burn wounds are evaluated, together with stimuli-responsive hydrogels capable of sensing wound microenvironmental cues such as reactive oxygen species, pH, and matrix metalloproteinase activity to enable microenvironment-responsive EV release, representing a transition from passive delivery toward more adaptive and controlled therapeutic strategies. Nevertheless, the current evidence is derived predominantly from in vitro and small-animal studies and is constrained by heterogeneous EV preparations, insufficient standardization of manufacturing and quality control, and limited clinical validation. Finally, critical challenges including production standardization, scalable manufacturing, and regulatory barriers to clinical translation are analyzed, and future directions for advancing hydrogel-EV systems toward clinical translation are discussed, aiming to provide insights and perspectives for further fundamental research and clinical translation of hydrogel-EV systems in skin wound healing.
SN - 2296-4185
ER -