Scarless Regeneration Following Third-Degree Burns in the Japanese Fire-Bellied Newt (Cynops pyrrhogaster)

Deep burn injuries in mammals typically heal with fibrosis and scar formation. Although the Japanese fire-bellied newt (Cynops pyrrhogaster) exhibits scarless skin regeneration after injury, whether this capacity is maintained after third-degree burn remains unclear. A third-degree burn model was established in adult newts, and the regenerative process was analysed over 1 year using macroscopic, histological, ultrastructural and molecular approaches. Blood cell dynamics and proliferative cells were evaluated by Wright-Giemsa staining and PCNA immunohistochemistry. Burn wounds were completely re-epithelialised by post-burn day (PBD) 8 despite persistence of damaged tissue. The wound subsequently underwent progressive tissue remodelling and closely resembled normal skin macroscopically by PBD 365 without evidence of contracture. Histological and ultrastructural analyses demonstrated restoration of organised dermal collagen architecture and muscle sarcomere structures without fibrotic scar formation. Erythrocytes transiently accumulated within damaged tissues and peaked on PBD 12, whereas neutrophils peaked earlier and declined after re-epithelialisation. PCNA-positive proliferative cells in the dermis and subcutaneous tissue peaked on PBD 30. Semi-quantitative RT-PCR suggested temporal changes in inflammatory marker expression during the regenerative process. Adult newts achieve scarless regeneration following third-degree burns. These findings establish a useful experimental model and provide a comprehensive characterisation of scarless regeneration following third-degree burns, providing a foundation for future mechanistic studies.