Tunable Biomimetic Hydrogels from Silk Fibroin and\nNanocellulose

Abstract

Biomimetic hydrogels\noffer a new platform for hierarchical structure-controlled,\ntough, biocompatible, mechanically tunable, and printable gels for\nregenerative medicine. Herein, we report for the first time the detailed\neffects of various kinds of nanocellulose, namely, bacterial nanocellulose, cellulose nanofibers, and cellulose nanocrystals\non the morphology, structure–property relationship, and 3D\nprintability of the photochemically cross-linked regenerated silk\nfibroin (RSF)/nanocellulose composite hydrogels. The hierarchical\nstructure of fabricated biomimetic hydrogels was both qualitatively\nand quantitatively investigated by scanning electron microscopy and\nsmall/ultrasmall-angle neutron scattering, whereas their mechanical\nproperties were assessed using rheology, tensile, and indentation\ntests. The micropore size and interhydrophobic domain distance of\nfabricated hydrogels were tuned in the range of 1.8–9.2 μm\nand 4.5–17.7 nm, respectively. The composite hydrogels exhibit\nsuperior viscoelastic, compressive, and tensile mechanical properties\ncompared to pristine RSF hydrogel, where the shear storage modulus,\ncompression modulus, young’s modulus, and tensile toughness\nwere tuned in the range of 0.4–1.4, 1.3–3.6, 2.2–14.0\nMPa, and 16.7–108.3 kJ/m³, respectively. Moreover,\nthe obtained mechanical modulus of the composite hydrogels in terms\nof shear, tensile, and compression are comparable to articular cartilage\n(0.4–1.6 MPa), native femoral artery (∼9.0 MPa), and\nhuman medial meniscus (∼1.0 MPa) tissues, respectively, which\ndemonstrate their potential for a wide range of tissue engineering\napplications. The whisker form of nanocellulose was observed to enhance\nthe printability of composite hydrogels, whereas the fiber form enhanced\nthe overall toughness of the composite hydrogels and promoted the\nfibroblast cell attachment, viability, and proliferation. The results\npresented here have implications for both fundamental understanding\nand potential applications of RSF/nanocellulose composite hydrogels\nfor 3D-printed scaffolds and tissue engineering.