A. A. Wick1, T. Lecy1, T. W. King1 1University Of Wisconsin,Plastic Surgery,Madison, WI, USA
Introduction:
Every year in the United States, more than 6.5 million patients suffer from wound-related complications, and treatment is estimated to cost over $25 billion. After an injury, keratinocytes from the wounded edge must proliferate, migrate across the wound bed, and differentiate in order to restore normal barrier function. We are interested in discovering new methods by which to enhance proliferation, migration, and differentiation in order to improve the wound healing process. Hesperidin, a natural flavonoid found in citrus fruits and honey, has been shown to improve epidermal barrier function. In this study, we investigated the effects of hesperidin on the rate of wound healing in murine splinted cutaneous excisional wounds, a model shown to simulate healing in human tissue.
Methods:
Six week old, male mice (n=14) were anesthetized, shaved, and two full-thickness 6 mm wounds were created on their backs under aseptic conditions. A 12 mm silicone stent was secured around each wound using cyanoacrylate glue and interrupted 5-0 nylon sutures in order to prevent healing by contraction and to promote healing by formation of granulation tissue. A sterile non-adherent dressing and transparent occlusive dressing were placed over the wound. Twenty-four hours after injury, hesperidin (10 μM) or vehicle (0.01% DMSO) was applied topically to each wound and was repeated daily. Digital photographs were taken of the wounds every day at each dressing change and treatment application. Wound closure was defined by gross visualization of resurfacing epithelia and calculated as a percent area of the original wound size. Wounds were quantified using ImageJ software (NIH) and expressed as a ratio of wound area to stent area, with scaling normalized to the inner diameter of the splint.
Results:
The wound sizes were similar in both groups at the beginning of treatment. Addition of hesperidin (10 μM) significantly accelerated the rate of wound closure compared to DMSO control on day 4 (% open, 44±3 vs 53±2 respectively, p<0.05) and on day 5 (% open, 23±3 vs 33±3 respectively, p<0.05). Wound closure for both groups was complete by day 8. No negative side effects were noted in the mice.
Conclusion:
Hesperidin accelerates cutaneous wound closure in our in vivo model. Based on this novel finding, further studies should evaluate the mechanisms by which hesperidin accelerates the wound healing process, possibly leading to the development of new and effective therapeutics for wound healing in patients.