Multifunctional Silk Vinyl Sulfone-based Hydrogel Scaffolds for Dynamic Material-cell Interactions

Biochemical and mechanical interactions between cells and the surrounding extracellular matrix influence cell behavior and fate. Mimicking these features in vitro has prompted the design and development of biomaterials, with continuing efforts to improve tailorable systems that also incorporate dynamic chemical functionalities. The majority of these chemistries have been incorporated into synthetic biomaterials, here we focus on modifications of silk protein with dynamic features achieved via enzymatic, "click", and photo-chemistries. The one-pot synthesis of vinyl sulfone modified silk (SilkVS) can be tuned to manipulate the degree of functionalization. The resultant modified protein-based material undergoes three different gelation mechanisms, enzymatic, "click", and light-induced, to generate hydrogels for in vitro cell culture. Further, the versatility of this chemical functionality is exploited to mimic cell-ECM interactions via the incorporation of bioactive peptides and proteins or by altering the mechanical properties of the material to guide cell behavior. SilkVS is well-suited for use in in vitro culture, providing a natural protein with both tunable biochemistry and mechanics.