The Use Of Mtor Inhibitors In Scar
Cristiane H. Squarize1, Liana P. Webber1, Brian Yip1, Ha Bin Park2, Rogerio M. Castilho2.
1University of Michigan, Ann Arbor, MI, USA, 2University of Michigan, ANN ARBOR, MI, USA.
Background: The repai of skin is a well-orchestrated process. Although healing is a tightly regulated, abnormal tissue repair often lead to the unwanted formation of scars causing aesthetic and functional problems. Although scarring is a significant health problem and directly impact the human’s well-being, effective treatment options are lacking. There is a critical need for the identification of novel therapies to treat scars. Objective: To determine the clinical effects of topical administration of rapamycin gel as a strategy to mitigate scarring in vivo. Methods: Balb/c mice (n=24) were randomly assigned to control and experimental groups in which the formation of scars was induced using a mechanotransduction scar animal model. Topical rapamycin gel and vehicle were administered daily on the scars. Histological parameters of scar were analyzed along with biomarkers for mTOR pathway activation and drug delivery efficacy. Immunofluorescence stainings were performed with antibodies against p-S6 protein, alpha-smooth muscle actin, and Periostin, as well as the identification of collagen deposition using picrosirius staining. Results: Scar tissues displayed mTOR pathway activation along with increased vascularity and Periostin. Topical administration of rapamycin gel resulted in small scar formation as confirmed by the reduced distances between adipose tissues, muscles, and hair follicles. Rapamycin gel influenced blood vessels and Periostin deposition and preserved architecture of the stromal.
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