Establishing synergistic role of acacia honey and vitamin C: A promising strategy for faster wound tissue regeneration.

Being established as an important natural component for wound healing, acacia honey (AH) in combination with ascorbic acid (AA) was evaluated for its tissue regenerative properties to establish a synergistic effect. A thermosensitive hydrogel formulation was developed and characterized for viscosity, mucoadhesion, moisture retention, pH, and morphology, where the parameters were found to be favourable for topical application and longer retention. The porosity and swelling of the hydrogel matrix allow for prolonged and sustained release of AH and AA. The release patterns of AH and AA from the gel matrix followed the Korsmeyer-Peppas and Michaelis-Menten patterns, respectively, indicating sustained release. The optimized formulation revealed antimicrobial properties, as evidenced by the significant increase (p < 0.05) in the diameter of the zone of inhibition. Scratch wound assay using HaCaT cell line showed wound healing potential of 90.6±4.5% for the co-loaded formulation. Furthermore, the wound healing potential of the co-loaded hydrogel in the excision wound model in experimental rats could be linked to increased vascularization due to the daily application of the formulation at the wound site. The antioxidant capacity was demonstrated by decreased IC50 values of 53.75±5.9 and 72.71±6.63 µg/mL against ABTS and DPPH, respectively, which additionally supported the wound healing potential. Lastly, the synergistic role of AH and AA facilitates fibroblast proliferation, collagen production, and glycosaminoglycan deposition, which could be correlated with a significant increase in hexosamine and hexuronic acid to 153.3±9.49 and 48.91±6.84 µg/40 mg of wound tissue, respectively. Overall, the co-loaded hydrogel could be an effective alternative for the treatment of acute dermal injuries.