Table 2.

Examples of honey hydrogel-based wound dressings, methods of formation, evaluated models and main findings.

Honey Hydrogel Formulation			In Vivo Wound and Burn Model			Findings	References
Incorporated Honey	Hydrogel Matrix	Method of Hydrogel Formation	Type of Mice	Location of Lesson	Type of Wound/Burn
6% (v/v) Gelam (Melaleuca Apis melífera) honey (Malaysia)	PVP 15% (w/v), PEG 1% (v/v), protein-free agar solution 1% (w/v).	Electron beam irradiation (25 kGy)	96 male Sprague Dawley rats	Dorsum of rat	Deep partial thickness burn wounds	Good transparency; slightly acidic (pH 4.3); high capabilities in absorbing fluid. Significant acceleration of dermal repair and advanced re-epithelialization. Modulation of proinflammatory cytokines in wound healing. Synergistic effect of hydrogel matrix and incorporated honey.	[99]
Up to 3.5 % (w/w) Iran honey	PVA 10 % (w/w), CM-chitosan up to 3.5 % (w/w), water 85 % (w/w).	60Co Gamma-ray (radiation method) up to 40 kGy; 60Co Gamma-ray followed by 3 cycles of freeze–thawing (combinational method).	male NMRI mice	Dorsum of mice	0.7 cm × 0.7 cm wound	Acceptable swelling degree, transparency and inhibition of the growth of E. coli bacteria. The hydrogel containing more honey in its formulation has a more effective action in the wound healing process of the mouse. The mechanical strength of the hydrogels prepared by the combinational method was higher than by radiation method.	[100]
70% honey-based alginate hydrogel	Alginate hydrogel	-	20 male Wistar rats	Side of vertebral column between the ears	Full-thickness wound (1 cm × 1 cm)	Epiderm growth (after 21 days) and collagen synthesis (after 14 days). Wound-healing influences were attributed to the synergistic effect of the alginate hydrogel and the incorporated honey.	[101]
15 wt% PVA/chitosan nanoclay hydrogel	PVA 10% (w/w), Chitosan 2% (w/w), TPP (chitosan crosslinking agent), Montmorillonite up to 3 wt%, Acetic acid solution 2% (v/v)	Freeze–thawing method (freezing at −15 °C/24 h and subsequently thawing at room temperature for 24 h).	15 female mice	Dorsum	Full-thickness wound (1 cm × 1 cm)	Honey-loaded hydrogel nanocomposite wound dressings (PCMH) had better wound-healing ability than nanoclay hydrogel without honey (PCM) and hydrogel without nanoclay and honey (control group). The wound size reduction at the third post-operation day was: 39.62% (control), 39.62% (PCM), and 39.62% (PCMH); at the sixth day: 55.23% (control), 58.38% (PCM), and 72.60% (PCMH).	[102]
10% and 20% (v/v) Chicory honey (Iran)	Chitosan, gelatin 5% (w/v), PVA 10% (w/v), acetic acid 3% (w/v); Ratio of 2:1:1 (v/v/v) chitosan, PVA, gelatin solution	3 cycles of freeze–thawing (freezing at −20 °C for 20 h, and subsequently thawing at 25 °C for 4 h)	18 male Wistar rats	Back of rats	Full thickness excisional wounds (2 cm × 2 cm)	The higher concentration of honey in the hydrogel facilitated the wound-healing process from inflammation to proliferation, and finally, to the maturation phase. Almost 50% wound closure was observed after 4 days (20% v/v honey); and 95% after 12 days (10 and 20% v/v honey).	[103]
20 g of diluted (50:50 w/w) raw sunflower honey (China)	Chitosan, gelatin, honey (ratio of 0.5:20:20, w/w/w). Distilled water up to 100 g (final volume).	Standing and cooling to room temperature. Sterilization of hydrogel sheets with UV rays for 45 min.	4 male rabbits	Dorsum	Second degree burn wound (3 cm × 3 cm)	On day 12, the burns treated with honey hydrogel sheets (HS) were completely healed with intact epidermis and topical proliferation of hair follicles. In contrast, MEBO-treated burns (commercial ointment) and non-treated burns presented 15% and63% unclosed wound area, respectively.	[104]
Solution (1:1, v/v) of liquid Manuka honey (New Zealand)	pectin	Hot-air-dried at 40 °C and conditioned in air drier at 25 °C for 5 days. Sterilization by gamma-irradiation at 25 kGray	36 male Sprague Dawley rats	Dorsum	Full thickness excisional wounds (2 cm × 2 cm)	Topical administration of pectin and pectin-honey hydrogels accelerate wound healing in rats. On the 23rd day, the entire surface of the lesion treated with the dressing was covered with hair follicles and matured fibrous tissue.	[105]
Honey (Egypt) Up to 75% (w/w)	Carbopol 934, Chitosan, Methyl paraben, TEA, GAA, purified water.	Cold mechanical method (placed in refrigerator)	10 albino mice	Dorsum	Third-degree burn type with a focal wide area of necrosis in the epidermis	Honey 75%-chitosan formula showed the best healing properties (regeneration of the epidermis tissue and the formation of new blood capillaries) compared to the pure honey and the commercial product tested (silver sulphadiazine).	[106]
Manuka honey 80% w/w)	PVA, borax (crosslinking agent)	Solution was molded in Petri dishes and kept at 50 °C overnight.	-	-	-	A wound dressing hybrid hydrogel with sustained release of honey over 24 h and with progressively low adhesion to the wound bed that protects new epithelialization and promotes cell proliferation. Antibacterial activity observed against the tested S. aureus.	[107]