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

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.

Amazonian Guarana- and Açai-Conjugated Extracts Improve Scratched Fibroblast Healing and Eisenia fetida Surgical Tail Amputation by Modulating Oxidative Metabolism

“…Some of these molecules appear to have healing properties, including EGCG [42] and gallic acid [43]. In addition, gallic acid, EGCG, and caffeine seem to act against complications related to healing processes, such as keloid formation [44][45][46].…”

Toosendanin‐induced apoptosis of CMT‐U27 is mediated through the mitochondrial apoptotic pathway

“…Images of the scratched areas of each treatment group were captured using an inverted microscope (10×, Olympus IX53/DP80, Japan) at 0 and 48 h. The wound healing areas of each treatment group were measured by ImageJ software (version 1.51j8, NIH, USA). The migration ratio was calculated using the following equation: 24 …”

Significant Benefits of Environmentally Friendly Hydrosols from Tropaeolum majus L. Seeds with Multiple Biological Activities

“…We believe that the reason for the different healing effects of the HYs should due to the specific composition of each extract. Moreover, the negative impact of the T. majus MHG HY on wound healing could be an interesting effect, because other substances that show a negative effect on wound healing, like caffeine [36] and allicin, are considered to be a promising therapeutic candidates for keloid scars [37]. Nevertheless, the reason for the negative effect of 15 µg/mL of the T. majus HY isolated using MHG on wound healing remains unclear, and it should be a subject for further studies.…”