© 2015 Humbert et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Clinical Interventions in Aging 2015:10 387–403 Clinical Interventions in Aging Dovepress submit your manuscript | www.dovepress.com Dovepress 387 OrIgInAl reseArCh open access to scientific and medical research Open Access Full Text Article http://dx.doi.org/10.2147/CIA.S69752 Mécano-stimulation™ of the skin improves sagging score and induces beneicial functional modiication of the ibroblasts: clinical, biological, and histological evaluations Philippe humbert 1,2 Ferial Fanian 1,2 Thomas lihoreau 1,2 Adeline Jeudy 1,2 Ahmed elkhyat 1,2 sophie robin 3 Carol Courderot-Masuyer 3 hélène Tauzin 3 Christine lafforgue 1,2,4 Marek haftek 5 1 research and studies Center on the Integument (CERT), Department of Dermatology, Clinical Investigation Center (CIC 1431), Besançon University hospital; 2 InserM UMR1098, FED4234 IBCT, University of Franche-Comté, Besançon, France; 3 SARL BIOEXIGENCE, Besançon, France; 4 Dermopharmacology and Cosmetology Unit, University of Paris Sud, France; 5 University of Lyon 1, EA4169, Experimental, clinical and therapeutic aspects of the skin barrier function, INSERM US7 – CNRS UMS3453, Lyon, France Background: Loss of mechanical tension appears to be the major factor underlying decreased collagen synthesis in aged skin. Numerous in vitro studies have shown the impact of mechanical forces on fibroblasts through mechanotransduction, which consists of the conversion of mechanical signals to biochemical responses. Such responses are characterized by the modulation of gene expression coding not only for extracellular matrix components (collagens, elastin, etc.) but also for degradation enzymes (matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]). A new device providing a mechanical stimulation of the cutaneous and subcutaneous tissue has been used in a simple, blinded, controlled, and randomized study. Materials and methods: Thirty subjects (aged between 35 years and 50 years), with clinical signs of skin sagging, were randomly assigned to have a treatment on hemiface. After a total of 24 sessions with Mécano-Stimulation™, biopsies were performed on the treated side and control area for in vitro analysis (dosage of hyaluronic acid, elastin, type I collagen, MMP9; equivalent dermis retraction; GlaSbox ® ; n=10) and electron microscopy (n=10). Furthermore, before and after the treatment, clinical evaluations and self-assessment questionnaire were done. Results: In vitro analysis showed increases in hyaluronic acid, elastin, type I collagen, and MMP9 content along with an improvement of the migratory capacity of the fibroblasts on the treated side. Electron microscopy evaluations showed a clear dermal remodeling in relation with the activation of fibroblast activity. A significant improvement of different clinical signs associated with skin aging and the satisfaction of the subjects were observed, correlated with an improvement of the sagging cheek. Conclusion: Mécano-Stimulation is a noninvasive and safe technique delivered by flaps microbeats at various frequencies, which can significantly improve the skin trophicity. Results observed with objective measurements, ie, in vitro assessments and electron microscopy, confirm the firming and restructuring effect clinically observed. Keywords: skin rejuvenation, skin sagging, mechanical stimulation, fibroblast synthesis Introduction Fibroblasts are the most abundant cells in the dermis. They play a major role in synthesizing collagen and elastic fibers, glycoproteins, and proteoglycans in the extracellular matrix. They also develop contractile forces required for matrix remodeling and migration activities. Skin aging is characterized by changes in the function and structure of the dermis. With aging, the skin tends to become thinner, drier, and less elastic. Fibroblastic dysfunction is one of the main markers of skin aging. This abnormal proliferation, Correspondence: Philippe humbert Department of Dermatology, Research and studies Center on the Integument (CERT), CHRU MINJOZ, 3 Boulevard Fleming, Besançon, France email philippe.humbert@univ-fcomte.fr