Topical Focal Adhesion Kinase Inhibitor Promotes Skin Regeneration And Scar Prevention In A Preclinical Porcine Model
Britta A. Kuehlmann, Sun Hyung Kwon.
Stanford University, Stanford, CA, USA.
Background: Pharmacological inhibition of FAK attenuates hypertrophic scar (HTS) formation following deep dermal injury, however, clinical translation of FAK inhibitor (FAKI) therapy has been challenging. Here we evaluated the efficacy and safety of topical FAKI hydrogel therapy in a preclinical large animal model. Methods: Red Duroc pigs were used to create 8 deep partial-thickness wounds of 25cm2 per animal. Animals received either standard dressings, blank hydrogel alone (placebo), or FAKI-releasing hydrogel dressings. Dressings and hydrogels were changed every 2 days until the wounds closed and then every 4 days thereafter. Wound closure rate, HTS formation, and regrowth of hair follicles and skin appendages were evaluated over 6 months. Results: FAKI-treated wounds closed significantly faster on day 14±2.3 vs. day 24±1.6 for control wounds vs. 24±0.8 for placebo wounds (N=8, p<0.01). Scars were dramatically reduced with FAKI hydrogel treatment compared to untreated control or placebo wounds. Lower Visual Analog Scale scores indicated improved scar appearance evaluated at Day 90 and at Day 180 (control VAS=100 vs. placebo 93±4.6 vs. FAKI 58±6.5, N=8, p<0.001). FAKI-treated wounds regenerated skin appendages including hair follicles and eccrine glands. Lastly, the collagen architecture of FAKI-treated wound was very similar to the unwounded pig skin while collagen organization of untreated control and placebo wounds appeared randomly disorganized. Conclusions: Topically delivered FAKI was effective in improving wound healing and promoting regeneration in a large animal, and holds great potential for wound and scar management of large and deep dermal wounds.
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