Cellulose nanofibrils reinforced chitosan-gelatin based hydrogel loaded with nanoemulsion of oregano essential oil for diabetic wound healing assisted by low level laser therapy

Diabetic foot ulcers are imperfections in the process of wound healing due to hyperglycemic conditions. Here, a nanoemulgel fabricated with oregano essential oil nanoemulsion, assisted by low-level laser therapy, was investigated for its efficacy in diabetic wound healing. A hydrogel- based healing patch, fabricated using biological polymers namely chitosan and gelatin and, polyvinyl pyrollidone. The hydrogel was reinforced with cellulose nanofibrils for enhanced stability and barrier properties. Nanoemulsion of oregano essential oil, with an average particle size of 293.7 ± 8.3 nm, was prepared via homogenization with chitosan as the coating agent. Nanoemulsion impregnated hydrogel, termed as the nanoemulgel, was assessed for its physio-mechanical properties and healing efficiency. The strong linkages in nanoemulgel demonstrated its large swelling capacity, high mechanical strength, and maximum thermal stability. The optimized conditions for low-level laser therapy using 808 nm were 1 W. cm-2 and 5 min. The optimized drug concentration of 128 μg. mL-1 exhibited viability of NIH/3 T3 fibroblasts as 75.5 ± 1.2 % after 24 h. Cell migration assay demonstrated that dual therapy facilitated wound healing, with a maximum closure rate of 100 % at 48 h. In vivo results revealed the rapid healing effects of the dual therapy in diabetic rat models with foot ulcers: a maximum healing rate of 97.5 %, minimum scar formation, increased granulation, enhanced reepithelialization, and a drastic decrease in inflammation and neutrophil infiltration within the treatment period compared to monotherapy and control. In summary, the combinatorial therapy of nanoemulgel and low-level laser therapy is a promising regimen for managing diabetic foot ulcers with a rapid healing effect.