Background: Burns, unlike mechanical wounds, are characterized by secondary injury progression due to reduced dermal microcirculation, inflammation, and oxidative stress. The vertical progression of injury delays healing or reepithelialization and increases scar formation. There are no current FDA-approved therapies to reduce burn injury progression. A previous study in a rat comb burn model demonstrated that tadalafil, a phosphodiesterase 5 inhibitor used as a vasodilator to treat erectile dysfunction, reduces necrosis in the unburned interspaces compared with naproxen, NAC, or their combination. In this study, we tested whether tadalafil speeds reepithelialization and reduces scarring of deep partial thickness burns in a validated vertical progression porcine burn model.
Methods: A validated animal burn model was used to create 60 deep partial thickness burns on the backs and flanks of six anesthetized domestic pigs (25-30 kg) using an aluminum bar preheated to 80 degrees C for 20 seconds. After removing necrotic epidermis from the wounds to simulate blister formation and rupture, the pigs were randomly treated with 2.5mg oral tadalafil or a placebo within one hour of injury and once daily thereafter for six days, totaling seven treatments. All wounds were dressed, covered, and treated with topical triple antibiotic ointment every other day. Periodic imaging and full thickness biopsies were conducted to monitor healing over 28 days. Biopsies were subjected to histomorphometric analysis by a board-certified dermatopathologist masked to treatment assignment.
Results: The mean (SD) percentage wound reepithelialization of burns treated with tadalafil (n=60) and control (n=60) at days 15 and 18 were 91.6 (25.4)% vs 43.5 (43.8)% and 96.4 (15.8)% vs 75.7 (38.7)% (p<0.001 for both). The median (IQR) time to complete wound reepithelialization was a significant 3 days faster in burns treated with tadalafil, at 15 (15-15) vs 18 (15-28) days, p<0.001. After 28 days, scar depth was significantly less in burns treated with tadalafil (2.7 + 0.4 vs 3.7 + 0.6mm, p =0.005). There were no wound infections or systemic adverse events in any of the wounds or animals respectively.
Conclusion: Seven once daily treatments of oral tadalafil speeds reepithelialization and reduces scarring in porcine deep partial thickness burns.