Skin wound healing is a natural and intricate process taking place after injury, involving different sequential phases such as hemostasis, inflammatory, proliferative and remodeling that are associated with complex biochemical events. The interruption or failure of wound healing leads to chronic non-healing wounds or fibrosis-associated diseases constituting a major health problem where unfortunately medicines are not very effective. The objective of this study is to evaluate the capacity of Cicaderma® ointment to accelerate ulcer closure without fibrosis and to investigate wound healing dynamic processes. We used a necrotic ulcer model in mice induced by intradermal adriamycin injection and applied vaseline or Cicaderma® every 2 days from when the ulcer area is maximal (day 11). Topical application of Cicaderma® allowed a rapid recovery of mature epidermal structure, a more compact and organized dermis and collagen bundles compared to vaseline group. Furthermore, the expression of numerous cytokines/molecules in the ulcer is increased 11 days after adriamycin injection compared with healthy skin. Cicaderma® rapidly reduced the level of pro-inflammatory cytokines, mainly TNF-α and others of the TNF pathway which can be correlated to a decrease of polymorphonuclears recruitment. Interestingly, the modulation of inflammation through TNF-α, MIP-1α, IL-12, IL-4 and M-CSF was maintained 9 days after the first ointment application, facilitating the wound closure without affecting angiogenesis. These cytokines appear to be potential targets for therapeutic approaches in chronic wounds. Our results confirm the use of Cicaderma® to accelerate skin wound healing and open new avenues for sequential treatments to improve healing.
- animal models
- colony stimulating factors
- growth factors
- transforming growth factor (TGF)
- Received October 4, 2011.
- Revision received May 30, 2012.
- Accepted June 27, 2012.
- The American Society for Pharmacology and Experimental Therapeutics