TABLE 2.

Representative studies of engineered EVs for wound healing.

Study type	Wound model	EV type	Engineering approach	Loading material	Purpose of engineering	Hydrogel/delivery approach	Targeted mechanism	Main treatment effects
In vitro + in vivo (mouse)	STZ-induced diabetic mouse full-thickness skin wound	Endothelial progenitor cell-derived biomimetic nanovesicles	Lipid insertion	cRGD peptide	Enhance endothelial cell targeting and local delivery of EVs	Fe3+@PA-modified ADM/GelMA dual-network hydrogel	Modulation of oxidative stress and inflammation	Accelerated diabetic wound closure; increased neovascularization; enhanced collagen deposition and skin regeneration (Liu S. et al., 2024)
In vitro + in vivo (mouse)	db/db diabetic mouse skin wound	HEK293T-derived EVs	Transfection (virus)	Serpin	Restore deficient Serpin proteins in diabetic EVs and enhance their wound-repair activity	Local EV administration; no hydrogel	Restoration of Serpin deficiency; regulation of protease activity	Accelerated wound closure, enhanced re-epithelialization, and improved tissue repair (Park et al., 2022)
In vitro + in vivo (mouse)	db/db diabetic mouse full-thickness skin wound	MSC-derived EVs	Transfection (plasmid)	HOTAIR	Enrich EVs with HOTAIR to enhance pro-angiogenic activity	Local EV administration; no hydrogel	Upregulation of VEGF expression and promotion of angiogenic signaling	Enhanced angiogenesis, accelerated wound closure (Born et al., 2022)
In vitro + in vivo (mouse)	STZ-induced diabetic mouse full-thickness skin wound	ADSC-derived EVs	Transfection (virus)	BCL-2	Enhance angiogenesis and tissue repair	epsilon-poly-lysine and hyaluronic acid antimicrobial hydrogel	Enrichment of PI3K-Akt and AGE-RAGE signaling pathways; enhanced growth factor activity and angiogenesis; suppression of inflammatory cytokines (TNF-α and IL-6)	Accelerated diabetic wound healing; enhanced angiogenesis and cell proliferation; reduced inflammation (Ju et al., 2025)
In vitro + in vivo (rat)	Rat skin burn wound	MSC-derived EVs	Co-incubation	Iron oxide nanoparticle	Enable magnetic targeting and increase EV accumulation at the wound site	Systemic injection; no hydrogel	Magnetic targeting enhances EV accumulation at the wound site; upregulation of VEGFA and CXCL12 expression	Accelerated wound closure, enhanced angiogenesis and collagen deposition, increased re-epithelialization, and reduced scar formation (Li X. et al., 2020)
In vitro + in vivo (mouse)	db/db diabetic mouse skin wound	Macrophage-derived EVs	Exofect	MiR-425-5p	Enrich EVs with MiR-425-5p	Local EV administration; no hydrogel	miR-425-5p-mediated upregulation of adiponectin in dermal fibroblasts, promoting macrophage-fibroblast intercellular communication and keratinocyte proliferation	Accelerated diabetic wound closure and improved re-epithelialization (Park et al., 2024)
In vitro + in vivo (mouse)	Excisional wound and diabetic wound	HEK293T-derived EVs	Transfection (plasmid)	HIF-1α	Deliver stable HIF-1α to enhance hypoxia-responsive signaling and angiogenesis	Collagen sponge scaffold	Activation of HIF-1α signaling and upregulation of hypoxia-responsive angiogenic genes	Enhanced angiogenesis, accelerated wound closure (Jeon et al., 2025)
In vitro + in vivo (mouse)	Excisional wound and diabetic wound	HEK293T-derived EVs	Surface engineering Transfection (plasmid)	CBD	Enhance collagen binding, wound-site retention	Collagen sponge scaffold	CBD-mediated collagen targeting enhances EV retention and sustained local delivery	Enhanced angiogenesis, accelerated wound closure (Jeon et al., 2025)
In vitro	In vitro endothelial-cell model	MSC-derived EVs	mRNA Transfection	VEGF mRNA	Enrich EVs with VEGF mRNA	EV treatment in vitro; no hydrogel	VEGF-mediated activation of pro-angiogenic and anti-apoptotic signaling in endothelial cells	Enhanced endothelial cell survival, increased angiogenic activity (Zhang et al., 2026b)
In vitro + in vivo (mouse)	Mouse full-layer skin defect wound	BMSC-derived ApoEVs	Co-incubation	sPLA2-X	Modify ApoEV lipid metabolism to enhance macrophage uptak	Local EV administration; no hydrogel	sPLA2-X-mediated phospholipid hydrolysis increases resolvin D5 (RvD5) production, enhances macrophage uptake of ApoEVs, and suppresses TNF-α expression	Enhanced macrophage-mediated tissue repair (Qin et al., 2025)
In vitro + in vivo (mouse)	STZ-induced diabetic mouse full-thickness skin wound	ADSC-derived EVs	Transfection (virus)	Tβ4	Enrich ADSC-EVs with Tβ4 to alleviate cellular senescence	Separable GelMA/PEGDA microneedle patch with HA backing layer	Activation of the PTEN/PI3K/AKT signaling pathway to alleviate cellular senescence	Reversed cellular senescence, accelerated diabetic wound closure, enhanced angiogenesis and collagen deposition (Ding Y. et al., 2025)