Background and objectivesMicroneedling therapy is a widely used technique in dermatology. However, little is known about the underlying molecular effects of this therapy on extracellular matrix remodeling, wound healing, and inflammation. The aim of this study was to examine morphological and molecular changes caused by microneedling treatment in a standardized in vitro full-thickness 3D model of human skin.Materials and methodsA microneedling device was used to treat full-thickness 3D skin models. Specimens were harvested at specified time points and qRT-PCR and microarray studies were performed. Frozen sections were examined histologically.ResultsMicroneedling treatment caused morphological changes in the skin model resulting in an almost complete recovery of the epidermis five days after treatment. Microarray analysis identified an upregulation of genes that are associated with tissue remodeling and wound healing (e.g. COL3A1, COL8A1, TIMP3), epithelial proliferation and differentiation (KRT13, IGF1), immune cell recruitment (CCL11), and a member of the heat shock protein family (HSPB6). On the other hand, we detected a downregulation of pro-inflammatory cytokines (e.g. IL1α, IL1β, IL24, IL36γ, IL36RN), and antimicrobial peptides (e.g. S100A7A, DEFB4). These data were confirmed by independent RT-PCR analyses.ConclusionWe present for the first time the direct molecular effects of microneedling therapy on epidermal keratinocytes and dermal fibroblasts using a standardized 3D skin model. Treatment resulted in histological alterations and changed the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling. This data suggests that skin microneedling plays a role in dermal remodeling, increases epidermal differentiation, and might also have a direct effect on collagen synthesis. These findings may increase our understanding of the molecular mechanisms of human skin repair induced by microneedling therapy and will allow comparisons with competing applications, such as ablative laser therapies.

Background:The "Inflammation Theory of Ageing" identifies pro-inflammatory cytokines and oxidative damage as one cause of cellular and mitochondrial deterioration and aging. Cell-free blood cell secretome (BCS) also known as autologous conditioned serum (ACS) has shown anti-inflammatory and regenerative mode of action in musculoskeletal disorders and radicular compression. Aim: To confirm that BCS can improve signs of skin aging from a previous study in a multi-center setting. Methods: Prospective, one-armed, multi-center interventional therapeutic study. Ninety-five women with skin firmness loss were treated with four intra-dermal injection sessions in both cheeks at 0, 2, 4 and 6 weeks. BCS was processed with Exokine® medical device according to manufacturer's instructions. Primary endpoints were cutometric R0 and R3 at 12 and 24 weeks. GAIS, FACE-Q TM , Patient Attractivity Self-Assessment and safety were evaluated. Results: Mean skin firmness (R0) improved significantly from baseline 0.40 mm to 0.38 mm at week 12 and to 0.36 mm at week 24. Mean skin tiring (R3) improved significantly from baseline 0.45 mm to 0.42 mm at week 12 and to 0.40 at week 24. FACE-Q TM "Satisfaction with Skin" significantly improved from baseline to weeks 12, 24 and 48. So did "Satisfaction with Facial Appearance" and "Psychological and Social Function". "Satisfaction with Decision" and "Satisfaction with Outcome" were stable at week 24 and 48. At week 48 patients assessed their age 1.68 years younger vs Baseline. FACE-Q TM aging appraisal improves from Baseline 52.94 to 65.23 at week 48. GAIS, by both physicians and patients, confirm improvement of skin. Conclusion:For up to 48 weeks four intra-dermal injections with cell-free BCS increase facial skin firmness and resilience to tiring and patients' satisfaction with their facial appearance and skin. Patients perceive their face as younger. BCS has the ability to sustainably rejuvenate facial skin safely. Study Registration: Registration on German clinical trials register: DRKS00013014.

Purpose In vitro study on the molecular effects of post-treatment after micro-needling applications with a dexpanthenol-containing ointment (DCO) using 3D skin models. Patients and Methods In this in vitro study, full-thickness human 3D skin models were treated with a micro-needling device according to its clinical application. For post-treatment, some of the models were additionally treated with a dexpanthenol-containing ointment (DCO). Histological samples were taken at 0, 24 and 48 hours. Gene expression analysis was performed after 24 hours. Results Histological examination showed that DCO post-treated 3D skin models revealed a completed wound closure 24 hours after the micro-needling procedure. In contrast, DCO-untreated models still clearly exhibited the micro-needling lesions after the same period of time. After 48 hours, all models revealed a completed wound healing. In skin models that received micro-needling but no post-treatment with DCO, microarray analysis identified an upregulation of proinflammatory cytokines and chemokines and a downregulation of skin barrier and differentiation markers. In contrast, post-treatment with DCO leads to accelerated wound healing without affecting the initial inflammatory response caused by micro-needling, which leads to the subsequent collagen expression. This data was supported by qRT-PCR analyses. Conclusion Post-treatment with DCO accelerates epidermal wound healing after micro-needling of 3D skin models without impairing the immunostimulatory properties of micro-needling. These findings can help to optimise the aftercare routine after micro-needling procedures and to shorten the downtime for the patient after treatment.

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