TABLE 4.
Quantitative loading and release characteristics of representative hydrogel-EV systems for skin wound healing.
| Study | EV type | Hydrogel system | EV loading efficiency | Burst release | Cumulative release | Release kinetics | Post-release EV bioactivity | Wound- healing phases |
|---|---|---|---|---|---|---|---|---|
| (Shen et al., 2021) | BMSC-sEVs | Bilayer thiolated alginate/PEGDA (BSSPD) | NR | NR | ∼80% at day 7 (lower layer); ∼80% at day 9 (upper layer) | Sequential physical-diffusion release; different swelling/degradation rates | NR | B-sEVs for early inflammation/proliferation; miR-29b-3p-sEVs for late proliferation/maturation |
| (Li et al., 2021) | hUCMSC-derived EVs | Genipin-crosslinked hydrogel | NR | NR | >85% after 72 h | Sustained release; hydrogel degradation increased after 72 h | NR | NR |
| (Kwak et al., 2022) | M2 macrophage-derived EVs | Hydrolytically degradable PEG hydrogels | NR | Half-release time 8 h | Generally 100% 1–2 days before complete degradation | Tunable release over ∼6–27 days; release profile strongly correlates with hydrogel degradation | Released M2-EVs remained morphologically intact and functionally active for macrophage polarization | Overall kinetics matched initial inflammatory phase |
| (Xu et al., 2022) | hUCMSC-derived EVs | TGase-crosslinked recombinant human collagen III hydrogel | NR | NR | ∼80% at day 10 | Sustained release from TGase-crosslinked rhCol III | NR | NR |
| (Britton et al., 2024) | EVs | Q5 protein hydrogel | NR | 42% ± 1% at 1 h; 89% ± 5% at 2 h | Subsequent release ∼4% per day until 72 h | Biphasic; later linear phase R2 = 0.91 | NR | NR |
| (Lyu et al., 2024) | MSC-derived EVs | PGLADMA core/GelMA shell microneedle patch | NR | NR | 25.24% ± 0.66% at day 14; 31.19% ± 0.27% at day 21 | Ritger–Peppas: Q(t) = 3.93t^0.691; n = 0.691; anomalous diffusion/erosion transport | EVs remained structurally intact after 21-day release | Prolonged EV release aligned with proliferative phase |
| (Zhu et al., 2024) | 3D-cultured ADMSC-derived EVs | Hyaluronan hydrogel | NR | NR | >65.1% at 48 h | Sustained release; mathematical model NR | NR | NR |
| (Liu B. et al., 2025) | hUCMSC-derived EVs | Photocrosslinking methacrylated decellularized dermal matrix | NR | NR | Exo@AMCN300: 74.67% ± 4.72% at 120 h and 87.67% ± 2.08% at 168 h | NR | NR | NR |
| (Wang et al., 2025) | Hypoxia-preconditioned ADSC EVs | HB-PEG/HA-SH in situ hydrogel | NR | NR | >75% by day 15 | NR | Functional activity supported by uptake, scratch and tube-formation assays | NR |
| (Li S. et al., 2026) | Camel milk EVs | Thermosensitive hydrogel | NR | 43.2% ± 3.1% at 8 h | 81.7% ± 4.2% at 48 h | Higuchi R2 = 0.974 (best fit); diffusion-controlled release | NR | NR |
NR, Not reported. EV loading amount or input concentration was not interpreted as loading efficiency. Post-release EV bioactivity was recorded as NR when biological activity was not specifically evaluated using EVs after release from the hydrogel. Quantitative values were included only when explicitly reported in the original studies and were not estimated from graphical data.