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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.

the obstruction. In addition, arterial occlusion can result in serious irreversible vascular complications, such as skin necrosis and vision loss. 3 According to a recent literature review, 4 most filler associated blindness cases are caused by HA fillers (70%). In particular, when HA filler is injected into anatomical locations such as the nose, glabella, and forehead, the procedure should be performed with caution.In Korea, sales of injectable fillers to nonprofessionals are prohibited; however, the patient was a paramedic employee in a local primary hospital, which made the filler accessible to her. In other cases, injectable fillers have been easily purchased online worldwide. There are also products called the Do-It-Yourself kits for dermal fillers and patients are able to download unverified injection maps from the internet and perform the injections themselves by watching video tutorials. 5 Individuals should be aware of these unsupervised medical practices that can cause irreversible sequelae. Fortunately, our patient did not show any serious irreversible complications because of immediate proper management within 24 hours of the injection. This emphasizes that immediate proper medical intervention is necessary at the onset of symptom development.This case has an educational impact on the importance of filler-associated guidance and supervision, with the pathologic evidence of HA filler obstructing the vasculature. Considering the possible complications and risks they pose, it is necessary to set strict regulations on filler administration.

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