Combination 5-Fluorouracil and Microneedling Therapy for Wound Modification: A Histological Murine Study

Purpose: Microneedling has been shown to enhance the efficacy of topical 5-fluorouracil (5-FU) for the treatment of dermatologic malignancies that along with our anecdotal clinical success of combination treatments for scar modification led the authors to investigate the effect of 5-FU and microneedling on wound healing. The current study evaluates the clinical and histological impact of topical 5-FU and microneedling therapy, separately, and in combination in a murine model. Methods: This is a randomized controlled trial in which 20 mice were randomized to 4 treatment groups: group 1 (n = 5) controls, group 2 (n = 5) microneedling alone, group 3 (n = 5) 5-FU alone, and group 4 (n = 5) combination 5-FU and microneedling. The interventions of interest were carried out on postoperative day 5, 10, 15, and 20 after wound induction. The clinical and histological wound appearance was graded by blinded oculoplastic surgeons and a blinded dermatopathologist, respectively. Statistical analysis was performed using a Kruskal-Wallis test with Dunn test for individual comparisons of treatment groups. Results: Blinded grading of the wound healing appearance at early, intermediate, and late healing time points demonstrated a statistically significant difference at the intermediate time point only. Histological analysis demonstrated a relative increase in epidermal thickness, dermal inflammation, and fibrosis in the combination treatment group. Statistically significant differences among the groups were identified in the degree of lymphocytic inflammation and for the amount of granulomatous inflammation. Discussion: This study was the first of its kind to investigate combination treatment with 5-FU and microneedling on a histopathologic level. In a murine model, this combination treatment resulted in increased degrees of wound inflammation and fibrosis relative to controls, and each treatment alone suggesting a histological basis that may relate to clinical impact, although future study in this area, to better understand the impact of these changes, is needed. Conclusion: Combination treatment with 5-FU and microneedling results in a histological increase in the degree of wound inflammation and fibrosis relative to controls and each treatment alone.