title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Centre de Recherche sur la Peau Pierre Fabre, Hôtel Dieu, Toulouse, France. virginie.turlier@pierre-fabre.com
authors: Virginie
authors: V
authors: Turlier
authors: Alexandre
authors: A
authors: Delalleau
authors: Christiane
authors: C
authors: Casas
authors: Amandine
authors: A
authors: Rouquier
authors: Pascale
authors: P
authors: Bianchi
authors: Sandrine
authors: S
authors: Alvarez
authors: Gwendal
authors: G
authors: Josse
authors: Alain
authors: A
authors: Briant
authors: Serge
authors: S
authors: Dahan
authors: Christine
authors: C
authors: Saint-Martory
authors: Jennifer
authors: J
authors: Theunis
authors: Amel
authors: A
authors: Bensafi-Benaouda
authors: Arnaud
authors: A
authors: Degouy
authors: Anne-Marie
authors: AM
authors: Schmitt
authors: Daniel
authors: D
authors: Redoulès
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003094:Collagen / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D020342:Finite Element Analysis; D005786:Gene Expression Regulation; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D011347:Procollagen / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012879:Skin Physiological Phenomena; D013314:Stress, Mechanical; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D011347:Procollagen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D006820:Hyaluronic Acid; D003094:Collagen; D020782:Matrix Metalloproteinases