Table 4 Research protocols for assessing the hydrogels loaded with cell-conditioned medium in animal models of wound management
Animal model | Animal age, strain, health status | Wound type and size | Wounds/animal | Number of animals | Target groups | Control groups | Time course, including intermediate control points | Dressing change | Notes | Re-ference |
|---|---|---|---|---|---|---|---|---|---|---|
Murine | 20-month-old, C57BL/6J, healthy | Acute (full-thickness), diameter 10 mm | 1 | 12 | 1) GelMA + F12 group (n = 6); 2) GelMA + hypo-CM (n = 6); 3) GelMA + nor-CM (n = 6) | 1) Blank (n = 6); 2) GelMA (n = 6) | 0, 4, 8 and 12 days | - | [60] | |
4–5-month-old, C57BL/6, healthy | Acute (full-thickness excisional), diameter 6 mm | 1 | 60 | 1) CG hydrogel-embedded with CM (n = 10); 2) PVA hydrogel-embedded with CM (n = 11) | 1) No treatment (n = 12); 2) CG hydrogel (n = 9); 3) PVA hydrogel (n = 10); 4) CM (n = 8) | 3 and 14 days | - | [67] | ||
8-week-old, C57BL/6, diabetic | Acute, diameter 10 mm | 1 | 45 | 1) SA/BG-SA-PLGA (n = 9); 2) SA/BGSA-PLGAPFD (n = 9); 3) SA/BG-SACM-PLGA (n = 9); 4) SA/BG-SACM-PLGAPFD (n = 9) | 1) No treatment (n = 9) | 6, 12, and 18 days | - | [57] | ||
10-week-old, C57/BL6, healthy | Acute (full-thickness), diameter 5 mm | 1 | NA | 1) GV8 peptide hydrogel containing CM (n = NA) | 1) No treatment (n = NA); 2) GV8 peptide hydrogel (n = NA) | 0, 2, 5 and 7 days | - | [52] | ||
6-week-old, C57BL/6, healthy | Acute (burn), square wound area (with a side- length of 15 mm) | 1 | 72 | 1) CM-hydrogel (n = 18) | 1) uCM (n = 18); 2) CM (n = 18) | 4, 14, and 28 days | Twice per day | [64] | ||
6-week-old, C57BL/6 wild-type, diabetic | Acute (full-thickness splinting), diameter 6 mm | 4 | 14 | 1) Secretome-laden fusion hydrogel (n = NA) | 1) PBS (n = NA); 2) Secretome (n = NA); 3) Fusion hydrogel (n = NA) | 0, 2, 4, 6, 8 and 10 days | - | [70] | ||
10-12-week-old, C57BL/KsJ db/db, diabetic | Acute (full thickness), diameter 8 mm | 2 | 18 | 1) CM-gel (n = 6) | 1) Gel (n = 6); 2) Vaseline gauze (n = 6) | 0, 7 and 12 days | - | [63] | ||
C57, healthy | Acute (full-thickness), diameter 10 mm | 1 | NA | 1) CM-containing hydrogel (0,5%, n = NA); 2) CM-containing hydrogel (1%, n = NA); 3) CM-containing hydrogel (2%, n = NA) | 1) No treatment (n = NA) | 7,14 and 21 days | - | [69] | ||
16-week-old, db/db, diabetic | Acute (full-thickness), diameter 6 mm | 2 | NA | 1) CM0-containing bandage (n = 5–7); 2) CM1-containing bandage (n = 5–7); 3) CM2a-containing bandage (n = 5–7); 4) CM2c-containing bandage (n = 5–7) | 1) Control bandage (n = 5–7) | 0, 3, 5, 7 and 10 days | - | [53] | ||
6-week-old, BALB/c, healthy | Acute (full-thickness), diameter 8 mm | 2 | 12 | 1) AC (n = 3); 2) AEC (n = 3) | 1) AS (n = 3); 2) AES (n = 3) | 0, 2, 4, 7 and 14 days | - | [54] | ||
6-week-old, BALB/c, healthy | Acute (full-thickness), diameter 8 mm | 2 | 24 | 1) M2-CCM (n = 3); 2) M2-hFDM-CCM (n = 3) | 1) Serum-free media (negative control, n = 3); 2) 10%FBS-supplemented media (positive control, n = 3) | 0,7, and 14 days | Every 2–3 days | [58] | ||
2-month-old, BALB/c, healthy | Acute (full-thickness), diameter 10 mm | 1 | NA | 1) Collagen hydrogel containing 200 μg/mL DFCM-KM1 (n = NA); 2) Collagen hydrogel containing 400 μg/mL DFCM-KM (n = NA); 3) Collagen hydrogel containing 400 μg/mL DFCM-FM (n = NA); 4) Collagen hydrogel containing 800 μg/mL DFCM-FM(n = NA) | 1) No treatment (n = 6); 2) Collagen hydrogel (n = 6) | 0, 7, 14, and 17 days | Twice (at day 0 and at day 7) | [61] | ||
21-week-old, strain is not indicated, healthy | Acute (full-thickness), diameter 6 mm | 2 | NA | 1) Lyo-secretome-loaded alginate dressing (n = NA) | 2) Alginate dressing (n = NA) | 3, 7, 14, and 21 days | - | [56] | ||
5-week-old, ICR, diabetic | Acute (full-thickness), diameter 8 mm | 2 | NA | 1) Hydrogel containing normoxic CM (n = NA); 2) Hydrogel containing hypoxic CM (n = NA) | 1) Hydrogel containing standard medium (n = NA) | 0, 1, 3, 5, 7, and 9 days | - | [72] | ||
Rat | Adult, Sprague-Dawley, healthy | Acute (circular, full-thickness), diameter 10 mm | 1 | 36 | 1) Hydrogel containing CM (n = 9) | 1) Saline solution (n = 9); 2) CM (n = 9); 3) Hydrogel (n = 9) | 0, 3, 7, 10 and 14 days | - | [68] | |
Adult, Sprague-Dawley, healthy | Acute (full-thickess), diameter 15 mm | 3 | 20 | 1)Bioactive functional composite patches contained EMSCs-CM (n = NA) | 1) No treatment (n = NA); 2) Composite patches without EMSCs-CM (n = NA) | 14, 21, d 28 days | - | [66] | ||
Wistar, healthy | Acute (full-thickness), diameter 20 mm | 1 | 36 | 1) SA/G-V-CM group (n = 3); 2) SA/G-LL-37-CM (n = 3) | 1) PBS (n = 3); 2) SA/G-PBS (n = 3) | 0,7,14 and 21 days | - | [55] | ||
Wistar, healthy | Acute (full-thickness), diameter 20 mm | 1 | 36 | 1) Hydrogel loaded with NRF2-CM and combined with MSCs (n = 3); 2) Hydrogel loaded with V-CM and combined with MSCs (n = 3) | 1) PBS (n = 3); 2) MSCs (n = 3) | 0,7,14 and 21 days | - | [65] | ||
8-week-old, Wistar, healthy | Pedicled skin flap | 1 | 60 | 1) ECM hydrogel with CMe (n = 5) | 1) DMEM (n = 5); 2) ECM hydrogel (n = 5); 3) CMe (n = 5) | 7,14, and 28 days | - | [71] | ||
3-month-old, Wistar, healthy | Acute (burn), area of 4 cm2 | 1 | 40 | 1) MMSC secretome-based chitosan gel (n = 10) | 1) Control (medical Vaseline oil, n = 10); 2) Bepanthen Plus (cream for external use, n = 10); 3) Miramistin solution for topical application 0.01%, n = 10 | 4 and 7 days | The formulations were applied 24 h later and then daily for 3 days (n = 5) or 7 days (n = 5) in each group | Wound area contaminated with Staphylococcus aureus | [59] | |
Sheep | 6-8-month-old, Siamese long tail, healthy | Acute (full-thickness), area 20cm2 | 4 | 6 | 1) Collagen hydrogel loaded with DFCM (n = 6); 2) Collagen sponge scaffold with freshly harvested skin cell (n = 6); 3) Platelet-rich-plasma gel (n = 6) | 1) No treatment (n = 6) | 0, 7, 14 and 21 days | Thrice, in 7 day interval | [62] |