TABLE 5.
EVs complexed with hydrogels for wound healing.
| Wound type | The source of EVs | Hydrogel | Model | EV dose | Wound closure | Vascularization | Collagen deposition | Molecular markers | Other major findings |
|---|---|---|---|---|---|---|---|---|---|
| Full-thickness skin defect | Mo-inspired macrophage | GelMA | Rats | NR | Day 14 significantly accelerated | NR | NR | NR | Enhanced proliferation, migration, tube formation, and angiogenic factor expression (CD31, VEGF, PDGF); promoted M2 macrophage polarization; reduced wound area and increased epidermal thickness; promoted angiogenesis through the activation of the ERK1/2 signaling pathway (Deng et al., 2025) |
| Full-thickness skin defect | Fibroblast | GelMA | Mice | 9 × 109 particles/mL | Day 14 wound area: 0.62 mm2 (GelMA-EVs) vs. 3.12 mm2 (GelMA) vs. 4.40 mm2 (Control) | NR | NR | NR | Accelerated wound healing, with faster closure, enhanced epithelialization, increased vascularization, and reduced fibrosis (Galbiati et al., 2025) |
| Full-thickness skin defect | Royal jelly | SerMA | Mice | 25 μg/mL | Day 4: 54.5%; Day 7: 87.6%; Day 14: 96.8% | NR | NR | NR | Anti-inflammatory and antioxidant effects; promoted L929 cell proliferation and migration in vitro (Tan et al., 2023) |
| Full-thickness skin defect | hUCMSCs | CMCS/GP | Rats | 6 μg/300 μL | Day 14: 98.9% ± 1.2% (Hydrogel + EVs); 86.9% ± 3.6% (Hydrogel); 74.8% ± 4.3% (Control) | NR | NR | NR | Improved wound closure, re-epithelialization rates, collagen deposition in the wound sites, TNF-α and IL-1β decreased (Li et al., 2021) |
| Full-thickness skin defect | Youthful Brain | GelMA | Rats | 100 μg/mL | Day 14: ≈95% | NR | NR | NR | Promotes scarless healing in aged skin, encouraged collagen deposition, angiogenesis, epidermal and dermal regeneration, and folliculogenesis (Wu et al., 2025) |
| Full-thickness skin defect | Lactobacillus casei | Carboxymethyl chitosan/aldehyde-hyaluronic acid | Mice | NR | Day 3: >50%; Day 10: nearly complete healing | NR | NR | NR | Stimulation of cell proliferation, migration, and endothelial tube formation while suppressing macrophage-derived pro-inflammatory signals (Zhang S. et al., 2026) |
| Full-thickness skin defect | Dental pulp stem cells | GelMA | Mice | NR | Day 9: >90% (Gel-EVs); 71% (GelMA); 86% (EVs) | NR | NR | NR | MiR-486-5p EVs improved angiogenic activities of HUVECs by increasing the TGF-β1 expression and Smad2 phosphorylation, while decreasing the Smurf2 expression (Wang S. et al., 2026) |
| Full-thickness skin defect | Paris polyphylla var. yunnanensis | Polyvinyl pyrrolidone/carboxymethyl chitosan | Mice | NR | Day 7: 82.17% ± 5.44%; Day 14: 99.66% ± 0.42% | NR | NR | IL-1β, IL-6 and TNF-α: >1.5-fold decreased vs. model group; intracellular ROS: 50% decreased in high-concentration PPEV group vs. positive control | Reduced the expression of pro-inflammatory cytokines (Tang et al., 2025) |
| Full-thickness skin defect | Periosteum | NAGA/GelMA/Laponite/glycerol | Rats | NR | Day 14: significantly increased | NR | NR | NR | Enhanced the proliferation, migration, and tube formation of ECs in vitro (Han et al., 2022) |
| Diabetic wound | ADSCs | Epsilon-poly-lysine and hyaluronic acid | Mice | NR | Day 15: significantly accelerated | NR | NR | NR | Increased angiogenesis, increased collagen deposition, enhanced cell proliferation, reduced inflammation, and improved tissue architecture (Ju et al., 2025) |
| Diabetic wound | UCMSCs | GelMA | Rats | NR | Day 14: significantly accelerated | NR | NR | NR | Promoted HUVEC cell migration; increased the wound collagen content and re-epithelialization (Tang et al., 2023) |
| Diabetic wound | Platelet-rich plasma | Gelatin/β-cyclodextrin | Rats | NR | Day 14: significantly accelerated | NR | NR | NR | Activated of autophagy and inhibition of apoptosis in HUVECs and HSFs, induced the blood vessel creation, collagen formation and re-epithelialization (Shu et al., 2023) |
| Diabetic wound | ADSCs | Extracellular matrix hydrogel | Mice | 200 μg/mL | Day 14: 92% (ECM@Exo) vs. 50% (Control) | NR | NR | NR | Reduced inflammation and promotes angiogenesis, collagen deposition, cell proliferation, and migration (Song et al., 2023) |
| Diabetic wound | MSCs | Gelatin methacryloyl (Gel)/poly-L-lysine methacryloyl (PL)-5 hydrogel (Gel/PL-5) | Mice | NR | Day 14: significantly accelerated | NR | NR | NR | Stimulated HUVECs; exhibited angiogenesis and anti-inflammation (Wang et al., 2024) |
| Diabetic wound | Houttuynia cordata thunb | rhCOL3/3-APBA | Mice | NR | Significantly accelerated | NR | NR | NR | Improved angiogenesis, increased collagen deposition, and reduced inflammation; regulating both NF-κB and YAP pathways (Yang W. et al., 2025) |
| Diabetic wound | ADSCs | HAP/OCS/PEG/Ag-E | Mice | NR | Day 10: near-complete closure | NR | NR | NR | Promoted M2 macrophage polarization, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and accelerated wound healing with enhanced angiogenesis and collagen deposition; suppressed the Notch/NF-κB/NLRP3 signaling pathway (Zhang Y. et al., 2025) |
| Chronic inflammation wound | MSCs | CMCS/OHA | Mice | NR | Day 14: significantly accelerated | NR | NR | NR | Inhibited the secretion of inflammatory factors; promoted wound re-epithelization and collagen production (Yue et al., 2024) |
| Burn wound | ADSCs | ADA-aPF127 | Rats | NR | Day 21: significantly accelerated | NR | NR | NR | Accelerated epithelialization, promoting granulation tissue formation and collagen deposition, hair follicle regeneration, mitigating inflammatory responses, and facilitating enhanced neovascularization (Vipin and Kumar, 2025) |
| MRSA- infected wound | MSCs | pH/ROS-responsive hydrogel (GA-containing) | Mice | NR | Significantly accelerated | NR | NR | NR | Promoted angiogenesis, promoted epithelialization, antibacterial against MRSA (Chen X. et al., 2025) |
| MRSA-infected wound | Broccoli | Silk protein methacryloyl hydrogel | Mice | NR | Day 7: 76.89% ± 1.70%; Day 14: 99.29% ± 0.71% | NR | NR | NR | Improved angiogenesis, increased collagen deposition, NF-κB inhibition and M2 macrophage polarization (Duan et al., 2025) |
NR, Not reported. Quantitative values were included only when numerical data were explicitly reported in the original study; outcomes presented only qualitatively or graphically without directly extractable numerical values were recorded as NR.