Table 1.
Recent in vivo studies on natural hydrogels for diabetic wound healing.
| Ref. | Year | Polymer Source and Material |
Additional Functional Component (s) |
Synthesis Method | Diabetic Model | Therapeutic Effect |
|---|---|---|---|---|---|---|
| [59] | 2022 | Sodium alginate (2% w/v) hydrogel | Deferoxamine (560 μg/mL) and copper nanoparticles (200 μg/mL) | Ionic crosslinking with 0.1M CaCl2 | STZ-induced male C57BL/6 mice | Enhanced antimicrobial effect as well as angiogenesis by upregulation of HIF-1α and VEGF. Reduced inflammatory response. |
| [60] | 2021 | Sodium alginate/pectin (5% w/w) composite hydrogel | Simvastatin (20 mg/mL) | Combined solvent-casting and ionic crosslinking with 0.5% w/v CaCl2 | STZ-induced male Wistar rats | Accelerated wound closure due to the presence of SIM, which promoted re-epithelialization, fibroblast proliferation and collagen production. |
| [61] | 2021 | Silk nanofiber (1 wt%) hydrogel | Deferoxamine (60 μM and 120 μM) | Concentration-dilution-thermal incubation method | STZ-induced male Sprague−Dawley rats | Enhanced collagen deposition and wound healing rates: 80% on day 14, and 100% on day 21. Improved angiogenic and inflammatory responses. |
| [57] | 2020 | Sodium alginate (2–5% w/v) hydrogel | Polydeoxyribonucleotide (100 μg/mL) | Ionic crosslinking with CaCO3 | Male C57BLKS/J-db/db mice | Improved re-epithelialization and granulation tissue formation. Increased collagen production and angiogenesis. |
| [62] | 2019 | Sodium alginate (1.5% w/w) hydrogel | Edaravone-loaded Eudragit nanoparticles | Ionic crosslinking with 0.5% w/w CaCl2 | STZ-induced male C57BL/6 mice | Downregulation of reactive oxygen species favored accelerated wound healing. |
| [43] | 2019 | Gelatin (4% w/v)/hyaluronic acid (0.1% w/v) composite hydrogel | Thrombomodulin (9 and 15 μg) | Chemical crosslinking (0.05% EDC) | STZ-induced male C57BL/6JNarl mice | Enhanced granulation tissue formation, re-epithelialization, collagen deposition, and angiogenesis. |
| [46] | 2018 | Chitosan (6% w/v) hydrogel | D-(+) raffinose pentahydrate (290 mM) | Physical crosslinking in alkaline solution (8% w/v KOH) | STZ-induced female Wistar rats | Increased bactericidal effect and accelerated wound healing. |
| [52] | 2017 | Chitosan (2 wt. %) hydrogel | L-glutamic acid (0.25–1.0%) | Physical crosslinking in alkaline solution (1M NaOH) | STZ-induced male Wistar rats | Enhanced re-epithelialization, collagen deposition, and neovascularization. |
| [39] | 2016 | Chitosan/starch hydrogel | Chitosan silver nanoparticles (5 ppm Ag in 6.9 mg/mL chitosan) | Reductive alkylation crosslinking | Alloxan-induced male albino rats | Significantly improved wound healing rate. Increased bactericidal response. |
| [39] | 2016 | Collagen/alginate (50/50 w/w) hydrogel | Curcumin (1 wt.%) -loaded chitosan nanoparticles | Chemical crosslinking (EDC) | STZ-induced male Wistar rats | Reduced inflammation. Enhanced cell adhesion and proliferation. Accelerated wound closure. |
| [63] | 2016 | Gelatin/hydroxyphenyl propionic acid hydrogel (5 wt%) | Interleukin-8 (IL-8, 0.5 μg/mL) or macrophage inflammatory protein-3α (MIP-3α, 1 μg/mL) | Horseradish peroxidase (HRP)-catalyzed cross-linking | STZ-induced male ICR mice | Increased cell infiltration, re-epithelialization, neovascularization, and collagen deposition. |