Enhancing hair follicle regeneration by nonablative fractional laser: Assessment of irradiation parameters and tissue response

Background and Objective Identification of methods to enhance anagen entry can be helpful for alopecia. Recently, nonablative laser has been proposed as a potential treatment for alopecia. However, how the laser parameters affect stem cell activity, hair cycles and the associated side effects have not been well characterized. Here we examine the effects of irradiation parameters of 1,550‐nm fractional laser on hair cycles. Study Design/Materials and Methods The dorsal skin of eight‐week‐old female C57BL/6 mice with hair follicles in synchronized telogen was shaved and irradiated with a 1,550‐nm fractional erbium‐glass laser (Fraxel RE:STORE (SR1500) Laser System, Solta Medical, U.S.A.) with varied beam energies (5–35 mJ) and beam densities (500–3500 microthermal zones/cm2). The cutaneous changes were evaluated both grossly and histologically. Hair follicle stem cell activity was detected by BrdU incorporation and changes in gene expression were quantified by real‐time PCR. Results Direct thermal injury to hair follicles could be observed early after irradiation, especially at higher beam energy. Anagen induction in the irradiated skin showed an all‐or‐non change. Anagen induction and ulcer formation were affected by the combination of beam energy and density. The lowest beam energy of 5 mJ failed to promote anagen entry at all beam densities tested. As beam energy increased from 10 mJ to 35 mJ, we found a decreasing trend of beam density that could induce anagen entry within 7–9 days with activation of hair follicle stem cells. Beam density above the pro‐regeneration density could lead to ulcers and scarring followed by anagen entry in adjacent skin. Analysis of inflammatory cytokines, including TNF‐α, IL‐1β, and IL‐6, revealed that transient moderate inflammation was associated with anagen induction and intense prolonged inflammation preceded ulcer formation. Conclusion To avoid side effects of hair follicle injury and scarring, appropriate combination of beam energy and density is required. Parameters outside the therapeutic window can result in either no anagen promotion or ulcer formation. Lasers Surg. Med. 47:331–341, 2015. © 2015 Wiley Periodicals, Inc.