Silk Nanofiber Scaffolds with Multiple Angiogenic Cues to Accelerate Wound Regeneration

Niches with multiple physical and chemical cues can influence the fate of cells and tissues <i>in vivo</i>. Simulating the <i>in vivo</i> niche in the design of bioactive materials is a challenge, particularly to tune multiple cues simultaneously in the same system. Here, an assembly strategy was developed to regulate multiple cues in the same scaffold based on the use of two silk nanofiber components that respond differently during the fabrication processes. An aqueous solution containing the two components, amorphous silk nanofibers (ASNFs) and β-sheet-rich silk nanofibers (BSNFs), was sequentially treated with an electrical field and freeze-drying processes where the BSNFs oriented to the electrical field, while the ASNFs formed stable porous structures during the lyophilization process to impact the mechanical properties. Bioactive cargo, such as deferoxamine (DFO), was loaded on the BSNFs to enrich cell responses with the scaffolds. The <i>in vitro</i> results revealed that the loaded DFO and the anisotropic structures with improved mechanical properties resulted in better vascularization than those of the scaffolds without the anisotropic features. The multiple cues in the scaffolds provided angiogenic niches to accelerate wound healing.