Emerging silk fibroin materials and their applications: New functionality arising from innovations in silk crosslinking

The ability to reverse engineer the silkworm fiber has led to tremendous advancements in the field of silk materials over the last several decades, with silk fibroin materials applied to biomedical, food, and high technology industries. This progress is largely due to the ability to process silk into a regenerated silk fibroin solution that can be engineered into a variety of material formats and stabilized by the reintroduction of the non-covalent native β-sheet protein structure. The next revolution in silk materials involves stabilizing silk fibroin through covalent crosslinking and plasticization. These approaches have transformed silk into a material that is not only strong, but also elastic and flexible, making it compatible with modern fabrication approaches. This has significantly broadened silk material fabrication strategies to include photolithography, digital light processing, and extrusion-based 3D printing. As a result, silk can now be used in a range of applications including ocular prostheses, bio-adhesives, tissue engineering matrices, green biodegradable LEDs and batteries, on-skin and implantable sensors, and bioplastics. In this review, we discuss the evolution of crosslinking in silk materials, focusing on covalent tyrosine- and methacrylate-based crosslinks, and on the structural changes and crosslinking brough about by plasticizing silk using glycerol and calcium ions. We describe how advances in silk crosslinking led to the development of unique materials, paving the way for new fabrication approaches and applications across multiple industries, ushering in a new era of silk materials.