The effect of modifying the nanostructure of gelatin fiber scaffolds on early angiogenesis in vitro and in vivo

Early angiogenesis is one of the key challenges in tissue regeneration. Crosslinking mode and fiber diameter are critical factors to affect the adhesion and proliferation of cells. However, whether and how these two factors affect early angiogenesis remain largely unknown. To address the issue, the optimal crosslinking mode and fiber diameter of gelatin fiber membrane for early angiogenesisin vivoandin vitrowere explored in this work. Compared with the post crosslinked gelatin fiber membrane with the same fiber diameter, the 700 nm diameterin situcrosslinked gelatin fiber membrane was found to have smaller roughness (230.67 ± 19 nm) and stronger hydrophilicity (54.77° ± 1.2°), which were suitable for cell growth and adhesion. Moreover, thein situcrosslinked gelatin fiber membrane with a fiber diameter of 1000 nm had significant advantages in early angiogenesis over the two with fiber diameters of 500 and 700 nm by up-regulating the expression of Ang1, VEGF, and integrin-β1. Our findings indicated that thein situcrosslinked gelatin fiber membrane with a diameter of 1000 nm might solve the problem of insufficient blood supply in the early stage of soft tissue regeneration and has broad clinical application prospects in promoting tissue regeneration.