Injectable Silk Nanofiber Hydrogels for Sustained Release of Small-Molecule Drugs and Vascularization

Abstract

Strategies to control neovascularization in damaged tissues remain a key issue in regenerative medicine. Unlike most reported desferrioxamine (DFO)-loaded systems where DFO demonstrates a burst release, here we attain zero-order release behavior above 40 days. This outcome was achieved by blending DFO with silk nanofibers with special hydrophilic-hydrophobic properties. The special silk nanofibers showed strong physical binding capacity with DFO, avoiding chemical cross-linking. Using these new biomaterials in vivo in a rat wound model suggested that the DFO-loaded silk nanofiber hydrogel systems stimulated angiogenesis by the sustained release of DFO, but also facilitated cell migration and tissue ingrowth. These features resulted in faster formation of a blood vessel network in the wounds, as well improved healing when compared to the free DFO system. The DFO-loaded systems are also suitable for the regeneration of other tissues, such as nerve and bone, suggesting universality in the biomedical field.