Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin disorder resulting in severe skin fragility, frequent blisters, scarring, increased risk of squamous cell carcinomas and decreased life expectancy. RDEB results from autosomal recessive mutations in type VII collagen, which is a critical component of the basement membrane. Skin fragility can predispose patients to great morbidity and effective methods to prevent and treat these lesions are limited.Study Design/ Materials and Method: We report the case of a 27-year-old woman with a mosaic phenotype of RDEB who presented for management of large non-healing chronic erosions on her upper back and posterior neck. These areas were treated with deep fractional carbon dioxide (CO2) laser, which has been shown to help with collagen remodeling in other clinical scenarios. Immediately after treatment, topical poly-L-lactic acid (PLLA) was placed on the skin surface to act synergistically with the laser. Additionally, punch biopsies were performed to compare the collagen distribution in treated and untreated skin.Results: After seven treatments, she has had great clinical improvement with decreased bleeding during the procedure and decreased frequency of blistering. On hematoxylin and eosin staining, the untreated skin had abnormal collagen organization whereas the treated skin demonstrated a collagen distribution akin to normal skin. Furthermore, a Herovici stain was performed to differentiate mature (type I) versus immature (type III) collagen, with a notable shift in expression patterns between the treated and untreated samples. Samples were also evaluated for direct immunofluorescence for type VII collagen, which confirmed that the treated samples had increased type VII collagen compared to the untreated sample.Conclusion: This case illustrates the potential for fractional CO2 laser in combination with PLLA to aid in the normalization of collagen and the potential for a “mechanical” treatment to increase activity of collagen VII in select patients with RDEB.