title: Skin extracellular matrix stimulation following injection of a hyaluronic acid-based dermal filler in a rat model.
abstract: BACKGROUND
  Hyaluronic acid-based dermal fillers have gained rapid acceptance for treating facial wrinkles and deep tissue folds. Although their space-filling properties are well understood, this study evaluates the cellular and molecular changes in skin, as a secondary effect, following injection of a commercially available, 24-mg/ml, cross-linked hyaluronic acid-based filler (HYC-24L+) in a rodent model.
  
  
  METHODS
  Sprague-Dawley rats, aged 2 to 4 months, were injected intradermally with 20 μl of HYC-24L+ using a linear threading technique and followed to 12 weeks after injection. Untreated skin and saline injection were used as study controls. Enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction methods were used to investigate changes in the expression of several extracellular matrix proteins and genes over time.
  
  
  RESULTS
  HYC-24L+ significantly increased the protein expression levels of collagen types I and III in rat dermal tissue for up to 12 weeks. The ratio of collagen type III to type I protein, however, remained unchanged, suggesting maintenance of collagen homeostasis. A significant increase in dermal elastin after HYC-24L+ injection was also observed. Gene expression analysis confirmed that several genes associated with extracellular matrix production and assembly were also transiently up-regulated, and that these changes temporally preceded those observed at the protein level.
  
  
  CONCLUSIONS
  In addition to its well-understood space-filling function, as a secondary effect, the authors demonstrate that HYC-24L+ stimulates the production of several extracellular matrix components, including dermal collagen and elastin.
authors.affiliation: Goleta, Calif.; and Boca Raton, Fla. From Allergan, Inc., and Aesthetic Eyelid Plastic Surgery.
authors.forename: Sumit
authors.initials: S
authors.lastname: Paliwal
authors.forename: Steven
authors.initials: S
authors.lastname: Fagien
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Sun
authors.forename: Tyler
authors.initials: T
authors.lastname: Holt
authors.forename: Thomas
authors.initials: T
authors.lastname: Kim
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Hee
authors.forename: Dennis
authors.initials: D
authors.lastname: Van Epps
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Messina
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D004549:Elastin / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007271:Injections, Intradermal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D006820:Hyaluronic Acid; D004549:Elastin