Therapeutic candidates for keloid scars identified by qualitative review of scratch assay research for wound healing

PLoS One. 2021 Jun 18;16(6):e0253669. doi: 10.1371/journal.pone.0253669. eCollection 2021.

Abstract

The scratch assay is an in vitro technique used to analyze cell migration, proliferation, and cell-to-cell interaction. In the assay, cells are grown to confluence and then 'scratched' with a sterile instrument. For the cells in the leading edge, the resulting polarity induces migration and proliferation in attempt to 'heal' the modeled wound. Keloid scars are known to have an accelerated wound closure phenotype in the scratch assay, representing an overactivation of wound healing. We performed a qualitative review of the recent literature searching for inhibitors of scratch assay activity that were already available in topical formulations under the hypothesis that such compounds may offer therapeutic potential in keloid treatment. Although several shortcomings in the scratch assay literature were identified, caffeine and allicin successfully inhibited the scratch assay closure and inflammatory abnormalities in the commercially available keloid fibroblast cell line. Caffeine and allicin also impacted ATP production in keloid cells, most notably with inhibition of non-mitochondrial oxygen consumption. The traditional Chinese medicine, shikonin, was also successful in inhibiting scratch closure but displayed less dramatic impacts on metabolism. Together, our results partially summarize the strengths and limitations of current scratch assay literature and suggest clinical assessment of the therapeutic potential for these identified compounds against keloid scars may be warranted.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Biological Assay
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Humans
  • Keloid / drug therapy*
  • Keloid / physiopathology
  • Wound Healing / physiology*

Grants and funding

This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institutes of Health (NIH).