Work

Hydrogel-based delivery of extracellular vesicles for skin wound healing: design strategies, therapeutic mechanisms, and translational perspectives

Year: 2026

Type: review

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.

Source: Frontiers in Bioengineering and Biotechnology

DOI: 10.3389/fbioe.2026.1976532

Authors: Yuqiu Jin, Jun Lu, Jingping Wu, Yi Zuo, Huilan Zheng, Fengrui Cheng

Institution: Chengdu University of Traditional Chinese Medicine

Language: English

Topic: Wound Healing and Treatments

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801