Skin extracellular matrix stimulation following injection of a hyaluronic acid-based dermal filler in a rat model

Plast Reconstr Surg. 2014 Dec;134(6):1224-33. doi: 10.1097/PRS.0000000000000753.


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.

Conclusion: 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.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Biocompatible Materials / pharmacology*
  • Biomarkers / metabolism
  • Collagen Type I / metabolism*
  • Collagen Type III / metabolism*
  • Elastin / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Hyaluronic Acid / pharmacology*
  • Injections, Intradermal
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / drug effects*
  • Skin / metabolism


  • Biocompatible Materials
  • Biomarkers
  • Collagen Type I
  • Collagen Type III
  • Hyaluronic Acid
  • Elastin