ObjectiveThis study aimed to investigate the feasibility of three different concentrations of silk-fibroin porous scaffolds applied to oral soft-tissue thickeningin vivo.MethodsSilk-fibroin scaffolds with three different concentrations (1 wt%, 3 wt%, and 5 wt%; denoted as SF1, SF3, and SF5, respectively) were prepared by freeze drying and methanol enhancement. The scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and thermogravimetric analysis. Pore size, porosity, andin vitrodegradation rate were also evaluated. The three groups of scaffold materials (the experimental sides) and the collagen matrix (the control side) were implanted into the oral mucosa of New Zealand white rabbits. Changed in mucosa thickness before and 3 months after operation were compared. Thein vivometabolism and regeneration effect of each group were observed by histological hematoxylin-eosin (HE) and Masson staining.ResultsSEM showed that the three groups of scaffolds were all cross-linked porous structures. XRD and FTIR showed that the three scaffolds were dominated by a relatively stable Silk Ⅱ structure, which degraded more slowlyin vitro. Among them, SF3 had the largest pore size (133.40 μm±22.85 μm) and moderate porosity (90.05%±6.68%).In vivoresults showed that the thickening effect of SF1 was similar to that of the control group because of insufficient space-maintenance property. Meanwhile, the properties of SF3 and SF5 were more stable, and the thickening effect was significantly better than those of the control group. However, unlike SF5 that induced obvious inflammation, SF3 showed better degradation, more fibrosis and angiogenesis, and less inflammatory responsein vivo.ConclusionSilk-fibroin scaffolds can be applied to effectively thicken soft tissues, among which SF3 (3 wt%) silk fibroin scaffold exhibited the best physicochemical properties, histocompatibility, and mucosal-thickening effect.