Topical Cromolyn Sodium Reduces Post-burn Hypertrophic Scars In Female Red Duroc Pigs
Jayson W. Jay, Anesh Prasai, Amina El Ayadi, Christian Sommerhalder, Daniel Popp, Evan Ross, Elizabeth Blears, Guillermo Foncerrada, Christian Tapking, David N. Herndon, Celeste C. Finnerty.
University of Texas Medical Branch, Galveston, TX, USA.
Background: Painful, motion-limiting hypertrophic scars (HTS) form subsequent to protracted wound healing in patients with severe full-thickness burns and pose difficult treatment challenges. Newer evidence points to mast cells as important regulators of intricate signaling cascades during the initiation and progression of post-burn scars. Previous investigations have demonstrated increased mast cell densities in burn wounds and during the formation of HTS. Mast cell proteases contribute directly to myofibroblast differentiation and excessive proliferation in burn wounds. Methods: Cromolyn sodium (CS) is an FDA-approved mast cell stabilizer known to inhibit degranulation and has been successfully used to relieve detrimental symptoms associated with mast cell activation. Here, we directly applied a 4% topical emulsification of CS to the post-burn HTS of red Duroc pigs (n=6). 3D images and scar biopsies were obtained monthly. Results: Toluidine blue stained scar tissue showed that CS significantly reduced mast cell density (p<0.05) over time. Histologically, epidermal thickness was also significantly reduced in CS-treated wounds. 3D analysis demonstrated that CS reduced scar height and volume while scar perimeter increased (p<0.05), flattening the scar over time compared to vehicle treatment alone or autologous split-thickness skin grafts. Additionally, immunohistochemical analysis showed that CS treatment significantly minimized dermal fibroblast expression of the protease-activated receptor-2 (PAR2, p<0.05) further indicating that fibrotic phenotype may be driven by mast cell tryptase activation of PAR2. Conclusion: Together, this evidence suggests that localized mast cell stabilization may be an effective approach to reduce pathologic scarring following a severe burn.
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