Association between collagen production and mechanical stretching in dermal extracellular matrix: in vivo effect of cross-linked hyaluronic acid filler. A randomised, placebo-controlled study.

BACKGROUND: The effects of hyaluronic acid (HA) injection on tissue collagen anabolism are suggested to be related to the induction of mechanical stress, causing biochemical changes in skin physiology. OBJECTIVES: To ascertain the association between dermal mechanics modulated by a hyaluronic acid-based filler effect and metabolism. METHODS: Sixty females were randomised to receive a 0.5mL injection of HA gel or isotonic sodium chloride (control) in the arm. Skin biopsies were taken at baseline and after 1, 3 and 6 months. Protein and gene expression of procollagen, matrix metalloproteinases (MMP) and MMP tissue inhibitors (TIMP1) were measured blind by ELISA and qPCR, respectively. Injected volumes were measured by high-frequency ultrasound and radiofrequency analysis. Skin layer effects of injections were analysed by finite element digital modelling. RESULTS: One month after injection, the filler induced an increase in procollagen (p=0.0016) and TIMP-1 (p=0.0485) levels and relative gene expression of procollagen III and I isoforms compared with the controls. After 3 months, procollagen levels remained greater than in the controls (p=0.0005), whereas procollagen expression and TIMP-1 and MMP content were no longer different. Forty-three percent of the injected filler volume was found at 1 month, 26% after 3 months and 20% after 6 months. LIMITATIONS: The ultrasound imaging technique limited the scope of the investigation and precluded an evaluation of the action of the filler at the hypodermic level. CONCLUSIONS: Integrating both mechanical and biological aspects, our results suggest that mechanical stress generated by cross-linked HA plays a role in dermal cell biochemical response.

Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation.

The aim of this study is to quantify D. folliculorum colonisation in rosacea subtypes and age-matched controls and to determine the relationship between D. folliculorum load, rosacea subtype and skin innate immune system activation markers. We set up a multicentre, cross-sectional, prospective study in which 98 adults were included: 50 with facial rosacea, including 18 with erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR) and 48 age- and sex-matched healthy volunteers. Non-invasive facial samples were taken to quantify D. folliculorum infestation by quantitative PCR and evaluate inflammatory and immune markers. Analysis of the skin samples show that D. folliculorum was detected more frequently in rosacea patients than age-matched controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in rosacea patients than in healthy volunteers. Skin sample analysis showed a higher expression of genes encoding pro-inflammatory cytokines (Il-8, Il-1b, TNF-a) and inflammasome-related genes (NALP-3 and CASP-1) in rosacea, especially PPR. Overexpression of LL-37 and VEGF, as well as CD45RO, MPO and CD163, was observed, indicating broad immune system activation in patients with rosacea. In conclusion, D. folliculorum density is highly increased in patients with rosacea, irrespective of rosacea subtype. There appears to be an inverse relationship between D. folliculorum density and inflammation markers in the skin of rosacea patients, with clear differences between rosacea subtypes.

Assessment of the clinical efficacy of a hyaluronic acid-based deep wrinkle filler using new instrumental methods.

BACKGROUND: The efficacy of numerous hyaluronic acid (HA)-based fillers has been demonstrated by semi-quantitative and qualitative methods, useful in clinical practice, but poorly reliable. OBJECTIVE: To objectively evaluate the efficacy of a HA gel in treating nasolabial folds (NLFs) over a 9-12-month follow-up period. METHODS: A total of 47 adult patients with moderate to severe NLFs received one or two injections of HA gel. Efficacy was assessed by measuring NLF depth at time intervals up to 12 months subjectively by blind and open clinical scoring using the Lemperle scale, and objectively using skin replicas and in vivo 3D imaging methods. Tissue characterization and dermal thickness were also assessed using radiofrequency ultrasonography and high-resolution ultrasound imaging, respectively. RESULTS: The filler injection highly significantly decreased the depth of NLFs (p < 0.0001) at all time points, with an improvement of at least 1 grade in the Lemperle score in 77% and 89% of the subjects at 9 and 12 months, respectively. NLF volume measured on replicas and 3D images significantly decreased after injection and this improvement was maintained over 12 months. CONCLUSION: This HA gel is well tolerated and provides a significant and long-lasting correction of moderate to severe NLFs, as objectively demonstrated by instrumental methods.