Tunable Biomimetic Hydrogels from Silk Fibroin and Nanocellulose

Abstract

Biomimetic hydrogels offer a new platform for hierarchical structure controlled tough, biocompatible, mechanically tunable and printable gels for regenerative medicine. Herein we report for the first time, the detailed effects of various kinds of nanocellulose namely, bacterial nanocellulose (BC), cellulose nanofibers (CNF) and cellulose nanocrystals (CNC) on the morphology, structure-property relationship and 3D printability of the photochemically crosslinked regenerated silk fibroin (RSF)/nanocellulose composite hydrogels. The hierarchical structure of fabricated biomimetic hydrogels was both qualitatively and quantitatively investigated using scanning electron microscopy and small/ultra-small-angle neutron scattering, whereas their mechanical properties were assessed using rheology, tensile and indentation tests. The micropore size and inter-hydrophobic domain distance of fabricated hydrogels were tuned in the range of 1.8-9.2 µm and 4.5-17.7 nm, respectively. The composite hydrogels exhibit superior viscoelastic, compressive and tensile mechanical properties compared to pristine RSF hydrogel; where the shear storage modulus, compression modulus, young's modulus and tensile toughness were tuned in the range of 3 kJ/m 3 , respectively. Moreover, the obtained mechanical modulus of the composite hydrogels in terms of shear, tensile and compression are comparable to articular cartilage (0.4-1.6 MPa), native femoral artery (~9.0 MPa) and human medial meniscus (~ 1.0 MPa) tissues, respectively, which demonstrate their potential for a wide range of tissue engineering application. The whisker form of nanocellulose was observed to enhance the printability of composite hydrogels, whereas the fiber form enhanced the overall toughness of the composite hydrogels and promoted the fibroblast cell attachment, viability and proliferation. The results presented here have implications for both fundamental understanding and potential application of RSF/nanocellulose composite hydrogels for 3D printed scaffolds and tissue engineering.

Photo-Crosslinked Silk Fibroin for 3D Printing

“…A range of functional additives can be used to enhance the mechanical performance of the Ru(II)/persulfate-mediated photo-crosslinked silk fibroin hydrogels, including resilin, graphene oxide (GO), and cellulose [ 59 , 70 , 72 , 73 ]. Resilin is one of the most resilient (~92%) proteins, responsible for the jumping and flight of many insects [ 62 , 74 ].…”

“…Cellulose is sustainable and offers superior mechanical strength [ 70 ] and has been used as a useful additive for 3D printing [ 84 ]. The addition of bacterial cellulose dramatically increased the toughness of photo-crosslinked silk-cellulose composites to 108 kJ m −3 , six-fold higher than monolithic silk fibroin hydrogels (around 16.7 kJ m −3 ).…”

Bioinspired Materials for Wound Healing Application: The Potential of Silk Fibroin

“…Dorishetty et al presented biomimetic silk fibroin/cellulose hydrogels for a wide range of tissue engineering applications, including cartilage and meniscus, due to the achieved mechanical properties. For this purpose, the authors investigated the effect of different types of nanocellulose, such as bacterial nanocellulose and cellulose nanofibers, on morphology, structure and performances of the composite hydrogels [ 86 ].…”

3D printed hydrogels with oxidized cellulose nanofibers and silk fibroin for the proliferation of lung epithelial stem cells

“…Recently, Dorishetty et al reported for the first time the detailed effects of various kinds of nanocellulose, namely, BC, CNF, and CNC on the morphology, structure–property relationship, and 3D printability of the photochemically cross-linked SF/nanocellulose composite hydrogels. Results indicated that SF/BC composite hydrogel possessed the superior mechanical performance among the hydrogels (Dorishetty et al 2020 ). However, it has been found that clogging is experienced when pastes of cellulose nanofibers are used at high concentration (> 0.8%) in 3D printing, due to the large bunches of fibers.…”

“…Dorishetty et al developed the SF/BC inks which could achieve a maximum cellulose content of about 5 wt% and could only print two layers structure. Higher resolution with 3D stereoscopic construct was difficult to achieve due to limited cellulose in inks (Dorishetty et al 2020 ). Because TEMPO-mediated oxidation helps reduce the adhesion and provide electrostatic repulsions between microfibrils by introducing certain amount of carboxylate groups, which facilitates the dispersion of cellulose nanofibers, especially BC.…”