Innovative carboxymethyl chitosan-gelatin tissue adhesive films co-delivering ciprofloxacin and Matricaria chamomilla to prevent infection and accelerate wound healing.

There is a growing demand for multifunctional films that can conform to wound contours while actively promoting healing. Among them, film-based polymers stand out due to their mechanical strength, biodegradability, and therapeutic potential. Matricaria chamomilla and ciprofloxacin were added to carboxymethyl chitosan (CMCs) and gelatin (Gel) to create a novel antibacterial and regenerative film-based composition. The films were made using the solvent-casting method and were tested for tensile strength, scanning electron microscopy, and Fourier-transform infrared spectroscopy. In vitro studies indicated that the Z4 film had a sustained release profile, releasing 449 ± 25.73 μg of chamomile and 159 ± 19.41 μg of ciprofloxacin over 48 h. It demonstrated antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus by achieving both Minimum Bactericidal Concentration (MBC) and Minimum Inhibitory Concentration (MIC). The film did not cause any harm to NIH 3T3 fibroblasts and was highly hemocompatible (hemolysis rate < 5 %). The Z4 film had closed 91.33 ± 5.61 % of the wounds in a rat incisional wound model by day 14. This value was statistically comparable (p > 0.05) to the suture control group (95.46 ± 9.15 %). Histological and gene expression analyses confirmed accelerated healing, revealing diminished MMP9 expression, enhanced re-epithelialization, organized collagen deposition, and a notable up-regulation of VEGF (4.92-fold) and TGF-β1 (4.94-fold). The quantitative findings highlight the film's significant potential as a bioactive adhesive for therapeutic wound care, offering enhanced healing and infection control comparable to that of conventional sutures.