Background and aim: Up to now, proper wound care management has remained as an important clinical challenge. Chitosan nanosheets (CNSs) showed a great potential in tissue engineering, but our knowledge about their wound healing effectiveness is based on very limited data. Thus, the aim of this research was to evaluate the wound healing potential of CNSs and honey as a vehicle for these nanoparticles. Methods: The skin excisional wound injury model was made in adult male BALB/c mice ( n = 60) by creating two identical sized wounds (5mm) on either side of their dorsal midline. The animals were divided into five groups ( n = 12 each) as untreated control, honey, polyethylene glycol, and CNSs dissolved either in honey or polyethylene glycol. Animals were received their relative topical treatments twice per day for 14 consecutive days. Tissue sampling was carried out on days 4, 7, 10, and 14 post wounding. The histological parameters including inflammatory cells infiltration, fibroblast proliferation, re-epithelialization, granulation formation, and collagen formation were evaluated in all studied time points. Results: Compared to the control group, CNSs showed significant wound healing activities with lower inflammatory cells infiltration, higher fibroblastosis and new epithelium thickness, and greater granulation area and collagen fibers density in the ulcer bed. In addition, honey synergistically increased the wound healing activity of the studied nanoparticles. Conclusion: These results showed that CNSs have promising wound healing activity specially when dissolved with honey concurrently.
