Hydrogel wound dressings provide a moist environment, which promotes the formation of granulation tissue and epithelium in the wound area, accelerating the wound healing process. There have been numerous approaches to skin wound management and treatment, but the limitations of current methods highlight the need for more effective alternatives. A Chitosan polyherbal hydrogel integrated with AgNPs was synthesized to assess its wound-healing potential both in vitro and in vivo. The AgNPs were synthesized using Calotropis procera leaf extract and characterized via X-ray diffraction analysis (XRD), Scanning electron microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FT-IR). In swelling kinetic analysis, the hydrogel's weight reached its maximum at 8 h of incubation and began to decrease from 12 h up to 72 h (49 % ± 6.04). The hydrogel formulation demonstrated strong antimicrobial potential against E. coli and S. aureus with an inhibition zone of 18 mm and 25 mm, respectively. Furthermore, in mice studies, the formulation exhibited significant wound size reduction within 12 days, supported by histopathology analysis revealing higher angiogenic potential compared to commercial hydrogels. The concentrations of IL-6 and TNF-α in CS-polyherbal/AgNPs hydrogel were 500 pg/ml and 125 pg/ml, respectively. Additionally, a network pharmacology approach identified 11 chemical constituents in Aloe vera, Azadirachta indica, and Alternanthera brasiliana extracts, along with 326 potential targets, suggesting the superior wound healing properties of this formulation compared to commercially available hydrogels.
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