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

A B S T R A C T 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 acidbased filler effect and metabolism. Methods: Sixty females were randomised to receive a 0.5 mL 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.