Management of Facial Burn Scar using Repurposed FDA-Approved Drugs

BACKGROUND: Facial burn injuries cause scars and contractures that are not only responsible for disfigurement but also severe functional impairment affecting quality of life. The patients will suffer permanent facial disfigurements even with multiple complex reconstructive surgeries Conventional scar management has not worked for the management of face burn. We set up a pre-clinical face burn model. This was followed by genome wide sequencing studies which led to identification of novel molecular targets for intervention. FDA approved drugs were screened to identify two drugs (D1 & D2) for topical treatment during the early (day 14- 41) and late (day 42-84) post-burn phases. METHODS: White Yorkshire pigs (70-80lbs) were subjected to sever full thickness facial burn trauma (~50% face). Facial burn was treated with either a standard-of-care dressing (SoC) (n=5) or topical FDA repurposed drugs (n=5) twice weekly until d84. Progression of burn wound healing and scar formation was followed using a) digital photography b) laser speckle microperfusion imaging (LSI); c) Harmonic Ultrasound Imaging with Doppler (HUSD) for biomechanics; and d) CT for 3D reconstruction of the facial soft tissues and bone. Histopathological examination of the burn wounds and scar tissues was performed. RESULTS: Severe facial burn with bone involvement showed raised scars/contractures, cicatricial ectropion, eversion of the oral mucosa and lip (drooling), and orofacial contracture. Vascular and bone deficits (n=5) were characterized using LSI, HUSD and CT imaging. Objective scar analysis revealed a significant improvement in wound healing, reduced total scar areas and less skin contractures in drug-treated group compared to the control (n=5; p<0.01). A significant reduction of cictertial ectropion and oral eversion (improved oral competence) was observed in drug treated pigs. Tissue analyses revealed significant decrease in myofibroblast formation with normally distributed blood vessels in drug-treated group compared to the control (n=5; p<0.01). Overall, the post-burn face appeared markedly better in response to treatment. CONCLUSION: This work presents a highly relevant preclinical model to study severe facial scar contractures and related outcomes. Bioinformatic studies led to identification of candidate pathways for intervention which was followed by the successful repurposing use of FDA-approved drugs towards marked improvement of burn outcomes.