title: The reconstructed skin model as a new tool for investigating in vitro dermal fillers: increased fibroblast activity by hyaluronic acid.
abstract: BACKGROUND
  Clinical studies on dermal fillers have essentially focused upon visible improvement of skin quality and any eventual side effects, whereas very little is known about their detailed biological effects.
  
  
  OBJECTIVE
  New skin equivalent models were created to investigate the biological impact of hyaluronic acid (HA) fillers on the dermal compartment in vitro.
  
  
  METHODS
  Two different reconstructed skin models were developed to incorporate HA within the collagen fibers. In the mixed model, HA was distributed throughout the whole collagen gel whereas the HA was concentrated in the center of collagen gel in the inclusion model.
  
  
  RESULTS
  A comparison of the addition of fillers in two models of reconstructed skin has permitted a better understanding of the biological impact of HA fillers. Protein profiling of supernatants from both models suggested a regulation of MMP-1 secretion by fibroblasts as a function of HA volume, distribution in the dermis and degree of cross-linking. Immunostaining of the inclusion model revealed increased production of type I and III procollagens close to the cross-linked HA. Fibroblasts located in this area showed a fusiform morphology as well as an increase in -smooth actin expression. The observed increase in collagen production may thus result in part from tension in fibroblasts surrounding the cross-linked HA.
  
  
  CONCLUSIONS
  The inclusion reconstructed skin model, as compared to the mixed model, presented here, appears to be a useful tool for investigating the properties of various fillers in vitro and closer to the in vivo situation; our results show that HA fillers promote in vitro remodeling of the dermis by fibroblasts.
authors.forename: Sarah
authors.initials: S
authors.lastname: Girardeau-Hubert
authors.forename: Séverine
authors.initials: S
authors.lastname: Teluob
authors.forename: Hervé
authors.initials: H
authors.lastname: Pageon
authors.forename: Daniel
authors.initials: D
authors.lastname: Asselineau
mesh_terms: D000199:Actins / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D000067548:Dermal Fillers / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D015603:Keratinocytes; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008954:Models, Biological; D012879:Skin Physiological Phenomena
chemical_list: D000199:Actins; D024042:Collagen Type I; D024043:Collagen Type II; D000067548:Dermal Fillers; D006820:Hyaluronic Acid; D003094:Collagen; D020781:Matrix Metalloproteinase 1