Harnessing de novo Designed Ultrashort Self-Assembling Peptides and Silk Fibroin as Pre-Gels for Extrusion-Based Bioprinting

Silk fibroin (SF) hydrogels are widely used in tissue engineering, thanks to its tunable physicochemical properties, aqueous processability and cytocompatibility. However, the use of SF-based inks in extrusion-based bioprinting (EBB) is limited due to SF rheological properties. In this work, we used the de novo designed self-assembling ultrashort ionic-complementary constrained peptides (UICPs) to modulate the rheological profile of SF-based pre-gels. By leveraging the synergistic interaction between SF and UICPs, we successfully modulated the molecular assembly of the pre-gel, significantly enhancing the rheological properties without compromising the integrity of the system. The SF-UICP hybrid formulations were engineered to optimize hydrogelation kinetics and mechanical stability. Furthermore, hyaluronic acid (HA) was incorporated to refine the shear-thinning behavior of the pre-gel, facilitating high-fidelity deposition and reducing the spreading ratio during the extrusion process. Our results demonstrate that UICPs serve as effective enhancers of rheological profiles of SF for EBB. The SF-based biomaterial ink offers an alternative biomaterial for the 3D printing of scaffolds for tissue engineering and regenerative medicine applications.