Water‐insoluble amorphous silk fibroin scaffolds from aqueous solutions

Abstract Regenerated silk fibroin (RSF) is emerging as promising biomaterial for regeneration, drug delivery and optical devices, with continued demand for mild, all‐aqueous processes to control microstructure and the performance. Here, temperature control of assembly kinetics was introduced to prepare the water‐insoluble scaffolds from neutral aqueous solutions of RSF protein. Higher temperatures were used to accelerate the assembly rate of the silk fibroin protein chains in aqueous solution and during the lyophilization process, resulting in water‐insoluble scaffold formation. The scaffolds were mainly composed of amorphous states of the silk fibroin chains, endowing softer mechanical properties. These scaffolds also showed nanofibrous structures, improved cell proliferation in vitro and enhanced neovascularization and tissue regeneration in vivo than previously reported silk fibroin scaffolds. These results suggest utility of silk scaffolds in soft tissue regeneration.