Gene Expression During Surgical Scar Remodeling by Fractional Photothermolysis

Overview

This project aims to understand the molecular biology underlying the improvement of surgical scars treated by ablative fractional photothermolysis (FP). Previous human studies at MGH have shown that FP significantly improves the appearance and functionality of surgical and burn scars. At the Wellman Center, we have conducted a randomized, controlled study on linear surgical scars demonstrating the efficacy of FP to decrease the volume of hypertrophic scars, and to improve the appearance and texture of scars. However, the underlying mechanism of this therapeutic effect is unknown. It is clear that FP induces wound healing and remodeling of the normal skin surrounding microthermal zones (MTZs). Furthermore, other researchers have employed animal models using transgenic zebrafish and the mouse eye, and found that laser treatments induce changes in gene expression in specific cells. We propose to determine whether the effect of FP on scar improvement occurs via changes in patterns of local gene expression within the skin, specifically dermal fibroblasts. By characterizing these changes, we may be able to identify molecular mechanisms that both explain and contribute to the beneficial effects of FP in the surgical and traumatic scar. The molecular insights into the therapeutic effects of fractional laser photothermolysis may provide a basis for future therapeutic strategies to improve scar remodeling.

A prospective, open-label study in 10 healthy adults, ages 18-50, with abdominal scars will be pursued at the Clinical Research Unit at Wellman Center for Photomedicine (MGH). A side-by-side comparison of untreated vs. one topical treatment of ablative fractional photothermolysis in qualifying subjects will be made. Ten subjects will receive treatment on randomly-assigned portions of their scars, in addition to non-treated control sites. The primary measures of efficacy are (a) blinded evaluation of scar improvement from standard digital photographs taken before and after the treatments, (b) changes in scar volume (measured by 3D Image system) and/or scar width, and (c) a quantitative characterization of gene expression measured by mRNA expression levels from treated and untreated scars and control sites. The primary measures of side effects are inflammatory and pigmentary outcomes assessed by blind evaluation of digital photographs taken before and after the treatments. Another study endpoint includes histopathological examination and comparison of treated and untreated scars. An FDA-approved 10600 nm Fractional laser source will be used for laser exposures performed 2 months prior to 2 skin biopsies (each 24 mm x 4 mm) of treated and untreated scar sites. A control site, with no treatment will also be left for clinical, histological and molecular examination.