Abstract: Objective To observe the levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase -13 (MMP-13) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in wound exudate of patients with refractory wounds, and to analyze their predictive value for the clinical effect of negative pressure vacuum sealing drainage (VSD) combined with artificial dermal repair in the treatment of refractory wounds. 
Methods Sixty patients with refractory wounds were selected to be included in the refractory group, and 60 patients with common wounds in the same period were selected as the control group. VEGF, MMP-13 and TIMP-1 were detected in wound exudate of all people enrolled, and MMP-13/TIMP-1 values were calculated. Patients with refractory wounds were treated with VSD combined with artificial dermal repair, and the clinical effect was observed. The patients were subdivided into effective subgroup and ineffective subgroup according to the clinical effect. The levels of VEGF, MMP-13, TIMP-1 and MMP-13/TIMP-1 in wound exudate between the effective group and the ineffective group were compared. Logistic regression was used to analyze the impact of the above indexes on the efficacy of VSD combined with artificial dermal repair in the treatment of refractory wounds, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of the above indexes on the efficacy of VSD combined with artificial dermal repair in the treatment of refractory wounds. 
Results The levels of MMP-13 and MMP-13/TIMP-1 in refractory group were higher than those in control group, while VEGF and TIMP-1 levels were lower than those in control group (P＜0.05). In 60 patients with refractory wounds, VSD combined with artificial dermal repair was effective in 49 patients (81.67%) and ineffective in 11 patients (18.33%). The values of MMP-13 and MMP-13/TIMP-1 in the ineffective group were higher than those in the effective group, and the levels of VEGF and TIMP-1 were lower than those in the effective group (P＜0.05). Logistic regression analysis showed that MMP-13 (95%CI: 1.037-1.165) and MMP-13/TIMP-1 value (95%CI: 1.410-3.458) were risk factors for therapeutic effect in patients with refractory wounds (P＜0.05), while VEGF (95%CI: 0.972-0.995) and TIMP-1 (95%CI: 0.264-0.756) were protective factors (P＜0.05). By point two-line correlation analysis, the results showed that VEGF and TIMP-1 levels were positively correlated with the efficacy of VSD combined with artificial dermal repair in patients with refractory wounds (r=0.410, 0.448, P＜0.05), and that the MMP-13 level and MMP-13/TIMP-1 value were negatively correlated with the therapeutic effect (r=-0.477, 0.570, P＜0.05). ROC curve was drawn, and the results showed that VEGF (95%CI: 0.643-0.908), MMP-13 (95%CI: 0.706-0.986), TIMP-1 (95%CI: 0.712-0.943) levels and MMP-13/TIMP-1 values (95%CI: 0.712-0.943) levels and MMP-13/TIMP-1 values (95%CI: 0.829-0.981) had a certain predictive value in the treatment effect of refractory wounds (AUC=0.776, 0.846, 0.827, 0.905). 
Conclusion VEGF, MMP-13, TIMP-1 and MMP-13/TIMP-1 values in wound exudate can have an important impact on the efficacy of VSD combined with artificial dermal repair in the treatment of refractory wounds, and the therapeutic effect can be predicted early by measuring VEGF, MMP-13, TIMP-1 and MMP-13/TIMP-1 values in clinical practice. 

Key words: refractory wound, vascular endothelial growth factors, matrix metalloproteinase 13