Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin

Objective: To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO₂) laser resurfacing of photodamaged human skin. Design: Serial in vivo biochemical analyses after laser therapy. Setting: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. Subjects: Volunteer sample of 28 adults, 48 to 76 years old, with clinically evident photodamage of the forearms. Intervention: Focal CO₂ laser resurfacing of photodamaged forearms and serial biopsies at baseline and various times after treatment. Main Outcome Measures: Reverse transcriptase real-time polymerase chain reaction technology and immunohistochemistry were used to assess levels of type I and type III procollagens; matrix metalloproteinases (MMPs) 1, 3, 9, and 13; tropoelastin; fibrillin; primary cytokines interleukin 1β and tumor necrosis factor α; and profibrotic cytokine transforming growth factor β1. Results: Production of type I procollagen and type III procollagen messenger RNA peaked at 7.5 and 8.9 times baseline levels, respectively, 21 days after treatment and remained elevated for at least 6 months. Increases in messenger RNA levels of several cytokines (interleukin 1β, tumor necrosis factor a, and transforming growth factor β1) preceded and/or accompanied changes in collagen levels. Marked increases in messenger RNA levels of MMP-1 (39 130-fold), MMP-3 (1041-fold), MMP-9 (75-fold) , and MMP-13 (767-fold) were noted. Levels of fibrillin and tropoelastin rose in a delayed fashion several weeks after treatment. Conclusions: The biochemical changes seen after CO ₂ laser resurfacing proceed through a well-organized and highly reproducible wound healing response that results in marked alterations in dermal structure. These quantitative changes may serve as a means for comparison as other therapeutic modalities meant to improve the appearance of photodamaged skin are evaluated.