Cold-stimulated browning graft fat enhances burn wound recovery through accelerating DAMP-ADSC activation

Suboptimal skin regeneration in patients with severe burns leads to significant trauma. Due to their favorable biological properties, fat grafts have been widely used in wound repair. The present study aimed to investigate the regenerative benefits of cold-stimulated fat graft in a contact burn model using C57BL/6J mice. Transplantation of browning fat grafts, with enhanced adipogenic capacity and decreased fibrosis, effectively promoted granulation tissue thickness and re-epithelialization areas. Cold-stimulated fat graft had a significant accumulation of ADSCs, which migrated into wound skin. In adipocyte-deficient mice, the impaired wound-healing phenotype was reversed by browning fat graft. Cold-stimulated fat also exhibited higher levels of damage-associated molecular patterns (DAMPs), which induced the proliferation of ADSCs and promoted ADSC proliferation and differentiation into mature adipocytes. Inhibition of DAMP-related signaling abolished the repair benefits of browning fat graft. In conclusion, transplantation of cold-stimulated fat represents a highly effective strategy for treating burn wounds through promoting DAMP signaling and dermal adipose remodeling.