Objective To investigate the effect of silk fibroin hydrogel loaded with developmental endothelial locus-1(Del-1)nanoparticles on the healing of chronic skin wounds in mice.Methods The back skin of BALB/c mice(6-8 weeks old)was pressed with a magnet for 12 h and then relaxed for 12 h,for 4 consecutive days to establish a chronic pressure ulcer wound.After infliction,the mice were randomly divided into 3 groups(n=8),and the skin wounds were treated with PBS,silk fibroin hydrogel or Del-1 nanoparticles/silk fibroin hydrogel.The wound healing was recorded with camera to calculate the wound healing rate.In 9 d after treatment,HE and Masson staining were used to observe the wound healing,and immunofluorescence staining for CD 14 and TNF-α was used to compare the appearance frequency of skin macrophages and the expression of inflammatory factors.After Tert-butyl peroxide(TBHP)was used to stimulate mouse macrophage RAW 264.7 cells and mouse vascular endothelial C166 cells,C166 cells were transfected with lentival vector to overexpress Del-1.Crystal violet staining was used to observe the migration of macrophages.RT-qPCR was used to detect the expression of inflammatory factor IL-6.Results The wound healing was significantly faster in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group(P＜0.01).The expression levels of TNF-α and CD14 in the wound surface were lower(P＜0.01),but collagen deposition and tissue repair were better in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group(P＜0.01).In vitro experiments,macrophages migrated to endothelial cells stimulated by TBHP,but the migration rate of macrophages was significantly lower in the Del-1 overexpression group(P＜0.01).RT-qPCR confirmed that Del-1 inhibited the transcription of IL-6(P＜0.01).Conclusion Del-1 nanoparticles/silk fibroin hydrogel can significantly accelerate the healing of skin wounds,and its mechanism may be through promoting the regression of inflammation and tissue repair.