Silk: old material new excipient

Silk has been used by humans for more than 5,000 years, with silk sutures being its first biomedical use. Silk is now making inroads into advanced pharmaceutical and biomedical applications. Both top-down and bottom-up approaches can be applied to silk. The resulting aqueous silk solution can be processed into various material formats, including self-assembling silk hydrogels and nanoparticles. Here, we demonstrate the potential of self-assembling silk hydrogels for tissue engineering and silk nanoparticles for drug delivery. For example, we use sonication energy to programme the transition of the silk secondary structure from a random coil to a stable β-sheets configuration. It is thus possible to fine-tune self-assembling silk hydrogels to achieve space conformity in the absence of any silk hydrogel swelling and to support uniform cell distribution as well as cell viability. Furthermore, we demonstrate the potential of microfluidics for the continuous production of silk nanoparticles with tuned particle characteristics that impact intracellular trafficking and macrophage response. These silk nanoparticles are responsive to enzymes and pH to trigger drug release and carrier biodegradation. Overall, the biopolymer silk is emerging as a valuable thread for diverse biomedical applications.