TABLE 3.
Representative stimuli-responsive hydrogels for treatment of wound healing.
| Response signals | Core materials | Cargo/system type | Quantitative response characteristics | Wound-relevant efficacy | Responsive mechanisms |
|---|---|---|---|---|---|
| ROS | PVA-CS@HA | EV-loaded hydrogel | 95% release and 35% mass loss at 60 h under 0.01 M H2O2, versus 31.2% release and 7.9% mass loss in PBS; stimulus threshold/sensitivity and repeatability: NR | Promoted diabetic wound repair in vivo | Synthesizing and incorporating ROS-cleavable crosslinkers (Pan et al., 2026) |
| Glucose | rhCOL3/3-aminophenylboronic acid | EV-loaded hydrogel | Stimulus threshold/sensitivity, response time, and repeatability: NR | Accelerated diabetic wound healing in vivo through modulation of NF-κB and YAP signaling | A boronate ester-crosslinked hydrogel responded to hyperglycemia (Yang W. et al., 2025) |
| MMP-9 | Oxidized dextran | EV-loaded hydrogel | Stimulus threshold/sensitivity, response time, and repeatability: NR | Promoted M2 macrophage polarization and diabetic wound repair in vivo | Cross-linking of oxidized dextran, a matrix metalloproteinase (MMP)-9-sensitive peptide (Meng et al., 2025) |
| Glucose and pH | HAP/OCS/PEG/Ag-E | EV-loaded hydrogel | Response evaluated at pH 5.5 and 33 mM glucose; structural response observed within 1 h at 37 °C; both conditions enhanced EV release; stimulus threshold/sensitivity and repeatability: NR | Accelerated diabetic wound healing with reduced inflammation and enhanced angiogenesis and collagen deposition | Hyaluronic acid-phenylboronic acid conjugate (HAP), enabling pH/glucose-responsive crosslinking via Schiff base (mainly pH-responsive) and phenylboronic ester bonds (both pH and glucose-responsive). Oxidized chondroitin sulfate (OCS) introduced aldehyde groups for additional Schiff base crosslinking, while its ortho-dihydroxy groups facilitated borate ester formation with HAP (Zhang Y. et al., 2025) |
| Glucose and oxidative stress | GPP@ZnBG | Non-EV cargo-loaded hydrogel (cargo zinc, calcium, and silicate ions) | Tested under 25 mM glucose and 100 μM H2O2; ion-release responses evaluated from 12 h to 14 days; stimulus threshold/sensitivity and repeatability: NR | Accelerated diabetic wound healing with improved neovascularization and enhanced collagen deposition | Upon exposure to pathological glucose/ROS levels, phenylboronate ester bonds cleave, triggering responsive degradation of the hydrogel matrix (Zhao et al., 2026) |
NR, Not reported. The non-EV system is included only as a design reference for potential adaptation to EV delivery. Quantitative stimulus concentrations represent experimentally tested conditions and should not be interpreted as validated response thresholds unless explicitly established in the original study.