Stepwise Cross-Linking of Fibroin and Hyaluronic for 3D Printing Flexible Scaffolds with Tunable Mechanical Properties

The development of 3D printing techniques has provided a promising platform to study tissue engineering and mechanobiology; however, the pursuit of printability limits the possibility of tailoring scaffolds’ mechanical properties. The brittleness of those scaffolds also hinders potential clinical application. To overcome these drawbacks, a double-network ink composed of only natural biomaterials is developed. A shear-thinning hydrogel made of silk fibroin (SF) and methacrylated hyaluronic acid (MAHA) presents a high mechanical modulus with a low concentration of macromers. The physical cross-linking due to protein folding further increases the strength of the scaffolds. The proposed SF/MAHA scaffold exhibits a storage modulus 10 times greater than that of methacrylated gelatin scaffold, along with better flexibility and biodegradation. The synergistic effect between fibroin and hyaluronic allows us to tailor the mechanical strength of scaffolds without compromising their printability. The hierarchy porous structure of the SF/MAHA scaffolds offers a better spatial microenvironment for the migration and proliferation of cells compared to gelatin scaffolds. For the first time, this strategy achieves 3D printing of natural biomaterials with controlled mechanical characteristics by manipulating the cross-linking of peptide chains. The design of such ductile scaffolds with hydrolysis resistance provides a new platform for the mechanobiology research. It also shows promise in the tissue engineering of musculoskeletal system where structural strength is needed.