Objective To construct a DNA-modified collagen(DNA-Col)scaffold to investigate the biocompatibility of the modified collagen(Col)and its performance in promoting the healing of oral mucosal soft tissue defects.Methods DNA-Col was constructed by chemical cross-linking methods by soaking Col materials in a buffer containing DNA and phosphate group activators.DNA crosslinked on DNA-Col was characterized by methyl green staining,and the cross-linking mechanism between DNA and Col was preliminarily explored by attenuated total reflection-Fourier transform infrared spectroscopy.The surface morphology of DNA-Col was observed by scanning electron microscopy.The biocompatibility of DNA-Col was evaluated by hemolysis test,CCK-8 cell proliferation assay and live/dead staining test.DNA-Col was then co-cultured with human oral fibroblasts in vitro,and the mRNA expression levels of transforming growth factor-β(TGF-β)and fibroblast growth factor-1(FGF-1)were detected by qRT-PCR,so as to analyze the potential of DNA-Col in promoting the healing of oral mucosal defects.Finally,the healing ability of DNA-Col was detected in the rat palatal mucosal defect model,and the mucosal healing of each group was analyzed by tissue sections 10 d after surgery.Results DNA-Col maintained the characteristic structure of Col and exhibited good biocompatibility.After co-culture of human oral fibroblasts with DNA-Col,the expressions of TGF-β,FGF-1 and other genes related to cell proliferation and migration were significantly increased,indicating that DNA-Col has the potential to promote oral mucosal healing.The rat palatal mucosal defect model showed that the wound healing rate of DNA-Col group was(97.04±2.07)%at 10 d after surgery,which was significantly higher than that of Col group[(79.38±5.76)%,P<0.01].Conclusion DNA-Col exhibits excellent biocompatibility and has the ability to promote the healing of oral mucosal soft tissue defects.