Treating a collagen scaffold with a low concentration of nicotine promoted angiogenesis and wound healing

Background: Nicotine, one of the major pharmacologically active agents of cigarette smoke, has various effects on cell proliferation, and it has recently been reported to have angiogenic effects. In our previous study, we showed that the topical administration of nicotine at a low concentration accelerated wound healing. This study aimed to evaluate the efficacy of nicotine and synergistic effects of combination treatment with nicotine and basic fibroblast growth factor (bFGF) in a murine excisional wound model treated with artificial dermis. Methods: Full-thickness defects (8 mm in diameter) were created on the backs of mice, and artificial dermis was sutured to the defects. Phosphate-buffered saline (10 mu L), nicotine (10(-3), 10(-4), or 10(-5) M), bFGF (0.5 mu g), and both bFGF and 10(-4) M nicotine were topically administered to the artificial dermal tissue for 7 d. The mice were killed on day 14, and the wound area, neoepithelium length, and area of newly formed capillaries in the artificial dermis were evaluated. Results: The wound areas treated with 10(-4) M nicotine, bFGF, or bFGF plus 10(-4) M nicotine were significantly smaller than those in the control group. In these three groups, the neoepithelium in the bFGF plus 10(-4) M nicotine group was significantly longer than that in the other groups. There was no significant difference between the neoepithelium lengths of the control and 10(-5) M nicotine groups. The 10(-3) M nicotine group displayed the least re-epithelization among the groups. Conclusions: In this study, 10(-4) M nicotine induced angiogenesis in, and accelerated the healing of, wounds treated with artificial dermis. bFGF and nicotine had synergistic effects, and the combined use of nicotine and bFGF is an effective wound healing method. (C) 2013 Elsevier Inc. All rights reserved.