Photodynamic Therapy Combined with Surgery: An Effective Treatment for Keloids via the YAP/Engrailed-1 Signaling Pathway

Yuan Ren,* Junbo Zhang,* Hao Jiang, Yuanyuan Wang, Yuangang Lu Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuangang Lu, Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China, Email skin515@qq.comObjective: Keloid, a unique human ailment, poses challenges in scar treatment due to variable efficacy and lengthy therapy and follow-up periods. Therefore, there is a need for a novel approach to address all forms of abnormal scarring. Photodynamic therapy (PDT), although slow-acting, shows promise, particularly when combined with surgery. This study aims to assess the efficacy and potential mechanism of PDT in conjunction with surgery for keloid treatment.Methods: Keloid patients were identified through pathological examination, and the expression of YAP and Engrailed-1 in keloid tissue was determined via immunohistochemistry. Initially, all keloids underwent treatment with 20% ALA-PDT as the initial therapeutic step (the preoperative photodynamic therapy margin extends 0.5 cm beyond the visible lesion edge to ensure full target tissue coverage), using red LED light with specific parameters. Subsequently, keloids were surgically excised 24 hours post-PDT, followed by another PDT session.Results: Immunohistochemistry assays revealed a significant reduction in YAP and Engrailed-1 levels in keloid tissues post-PDT. Over a minimum 6-month follow-up period, no infections, scar exacerbations, or recurrences were observed, except for postoperative hyperpigmentation.Conclusion: The combination of PDT and surgical therapy demonstrates promising results for keloid treatment. The suppression of YAP leading to reduced Engrailed-1 expression may represent a mechanism underlying the successful treatment of keloids with PDT.Keywords: keloid, photodynamic therapy, surgery, YAP and Engrailed-1