To investigate the effects and the potential mechanism of a composite scaffold constructed by human acellular amniotic membrane （HAAM） loaded with exosomes from adipose-derived mesenchymal stem cells （ADSCs-Exos） on full-thickness skin defect wound healing in mice.

ADSCs were isolated from adipose tissue obtained by liposuction， and ADSCs-Exos were collected and characterized. HAAM was prepared from placental amniotic tissue and characterized. Thirty-three BALB/c mice were selected to establish dorsal full-thickness skin defect models. In 9 mice, HAAM patches were sutured to the skin defects. The biodegradation of HAAM was evaluated by type Ⅳ collagen immunofluorescence staining of tissue sections on postoperative days 3, 7, and 14. The remaining 24 mice were divided into control group， HAAM group， Exos group， and Exos/HAAM group， with 6 mice per group. The control group received no treatment； the HAAM group was covered with HAAM patch； the Exos group was treated with 100 μg ADSCs-Exos； and the Exos/HAAM group was covered with HAAM patch containing 100 μg ADSCs-Exos. Wound healing was evaluated by morphological observation， hematoxylin-eosin （HE） staining， and Masson staining on days 7 and 14 post-surgery. Cytokine antibody microarray was performed on day 14 to detect the expression changes of chemokines at the wound site.

ADSCs-Exos were successfully isolated and identified. Scanning electron microscopy revealed a loose and porous structure of the HAAM scaffold. Immunofluorescence staining revealed that the HAAM had largely degraded by day 14 post-surgery. In the mice wound model， the Exos/HAAM group exhibited significantly higher wound healing rate on day 7 post-surgery compared to other groups. HE staining showed that the epithelialization in the Exos/HAAM group was better than that in other groups on day 7 post-surgery. Masson staining demonstrated that collagen content in the Exos/HAAM group was higher than that in other groups on day 14 post-surgery. Cytokine antibody microarray analysis indicated that the Exos/HAAM group exhibited superimposed expression of chemokines from both HAAM group and Exos group on day 14 post-surgery.

The Exos/HAAM composite scaffold promotes chemokine expression in wound tissue and accelerates wound healing in mice.