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

• Published in: Biochemistry (Moscow) Vol. 89; no. 5; pp. 942 - 957
• Main Authors: Rogovaya, Olga S., Abolin, Danila S., Cherkashina, Olga L., Smyslov, Artem D., Vorotelyak, Ekaterina A., Kalabusheva, Ekaterina P.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.05.2024; Springer Nature B.V
• Subjects: Animals; Antifibrotic Agents - pharmacology; Antifibrotic Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cell death; Cells, Cultured; Cicatrix - drug therapy; Cicatrix - metabolism; Cicatrix - pathology; Collagen; Collagen - metabolism; Contractility; Extracellular matrix; Fibers; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Humans; Incompatibility; Life Sciences; Male; Microbiology; Phenotypes; Regeneration; Skin; Skin - drug effects; Skin - metabolism; Skin - pathology; Thickness; Tissue engineering; Tissue Scaffolds - chemistry; Verteporfin - pharmacology; Verteporfin - therapeutic use; Wound healing; Wound Healing - drug effects; dermal fibroblasts; fibrosis; YAP/TAZ; verteporfin; skin regeneration
• ISSN: 0006-2979; 1608-3040; 1608-3040
• DOI: 10.1134/S0006297924050146

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.