In vitro and in vivo Evaluation of Antifibrotic Properties of Verteporfin in a Composition of a Collagen Scaffold

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Olga S. Rogovaya^1,a*, Danila S. Abolin¹, Olga L. Cherkashina¹, Artem D. Smyslov¹, Ekaterina A. Vorotelyak¹, and Ekaterina P. Kalabusheva¹

¹Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119334 Moscow, Russia

Received December 6, 2023; Revised March 5, 2024; Accepted March 31, 2024

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Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined in vivo and in vitro. In vitro effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. In vivo the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.

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KEY WORDS: dermal fibroblasts, fibrosis, skin regeneration, verteporfin, YAP/TAZ

DOI: 10.1134/S0006297924050146

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