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.

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Soy protein isolate (SPI), a plant derived protein is emerging as a potential material for biomedical applications. Herein we report the development and structure-property relationship of photocrosslinked SPI and SPI/silk fibroin (SF) hybrid hydrogels for the first time. The pristine SPI hydrogels were crosslinked at two different structural configurations (i.e. at pH 7 and 12), and SPI/SF hybrid hydrogels were co-crosslinked at pH 7 in three different weight ratios (3:1, 1:1 and 1:3). The fabricated hydrogels were characterized using electron microscopy, X-ray diffraction, Raman and infrared spectroscopy, thermal analysis, small and ultra-small angle neutron scattering, rheology, water uptake and in vitro degradation studies.The equilibrium water swollen SPI hydrogel photocrosslinked at pH 7 exhibited a particulate microstructure, controlled degradation in phosphate buffered saline, and a shear storage modulus of ~7.7 kPa, which is in the range of human lumbar nucleus pulposus, and significantly higher than soy hydrogels reported by thermal treatment, pressure treatment, saltinduced cold-setting and enzymatic crosslinking. Conversely, the SPI hydrogel photocrosslinked at pH 12 exhibited ordered porous microstructure, higher water uptake of ~1946%, and poor water-resistant and mechanical properties. Increase in SF content of the crosslinked SPI/SF hybrid hydrogels demonstrated improved porosity, swelling, molecular chain mobility, elastic and water-resistant properties. An in-depth understanding of the effect of pH and composition on the hierarchical structure and physicochemical properties of the fabricated hydrogels was established. Moreover, the SPI and SPI/SF hybrid inks used for photocrosslinking exhibited flow properties suitable for printing tissue engineering applications. The presented results contribute to a facile fabrication and fundamental understanding of the structure-property relationship of SPI-based hybrid hydrogels.

Charge-transfer (CT) gel materials obtained from low-molecular-weight (LMW) compounds through a supramolecular self-assembly approach have received fascinating attention by many researchers because of their interesting material property and potential applications. However, most of the CT gel materials constructed were of organogels while the construction of CT gels in the form of a hydrogel is a challenge because of the solubility issue in water, which considerably limits the use of CT hydrogels. Herein, for the first time, we report a new LMW gelator [N-(fluorenylmethoxycarbonyl)-N-(δ-butyric-1-pyrenyl)-l-lysine, (FmKPy)], composed of two functional moieties such as fluorenylmethoxycarbonyl and pyrene, which not only parade both hydro and organo (ambidextrous) supramolecular gel formation but also exhibit CT ambidextrous gels when mixed with an electron acceptor such as 2,4,7-trinitro-9-fluorenone (TNF). This finding is significant as the established CT organogelator in the literature did not form an organogel in the absence of an electron acceptor or lose their gelation property upon the addition of the acceptor. CT between pyrene and TNF was confirmed by the color change as well as the appearance of the CT band in the visible region of the absorption spectrum. CT between FmKPy and TNF was supported by the solvent dilution method using tetrahydrofuran as the gel breaker and pyrene fluorescence quenching in the case compound containing pyrene and TNF. The morphology of FmKPy ambidextrous gels indicates the fibrous nature while the self-assembled structure is primarily stabilized by π-π stacking among fluorenyl and pyrenyl moieties and hydrogen bonding between amide groups. The FmKPy-TNF CT ambidextrous gel retains the fibrous nature; however, the size of the fibers changed. In FmKPy-TNF CT gels, TNF is intercalated between pyrene moieties in the self-assembled structure as confirmed by fluorescence quenching and powder X-ray diffraction. The FmKPy ambidextrous gel exhibits significant properties such as low minimum gelation concentration (MGC), thixotropic nature, pH stimuli response, and high thermal stability. Upon the addition of TNF, the FmKPy-TNF CT ambidextrous gel maintains all these properties except MGC which increased for FmKPy-TNF. Because pyrene-based LMW organogels have been developed widely for many applications while their hydrogels were limited, the current finding of the pyrene-based ambidextrous fluorescent gel with the CT property provides a wide opportunity to use FmKPy as a soft material maker and also for potential applications in fields like surface coating, three-dimensional printing, and so forth.

Although a few Fmoc-functionalised amino acids (Fmoc-AA) are capable of forming hydrogels, the exact levels of hydrophobicity, hydrogen bonding, and ionic nature of the Fmoc-AA gelator required for hydrogel formation remains uncertain. Here, the role of hydrophobicity of amino acid side chain, particularly in the formation of hydrogel, was studied by using Fmoc-norleucine (Fmoc-Nle) and its simple sulfur analogues such as Fmoc-methionine (Fmoc-M) in which the γCH2 of Fmoc-Nle is replaced by sulfur. Results indicate that Fmoc-M forms thermally reversible hydrogels in water (pH ca. 6.8), whereas Fmoc-Nle fails to display any gelation under similar conditions. The result suggests that substitution of the sulfur atom likely reduces the hydrophobicity of the alkyl side chain in Fmoc-Nle to the optimum level, which is sufficient to induce supramolecular hydrogelation in Fmoc-M. The difference in the self-association behaviour of Fmoc-M and Fmoc-Nle emphasise the importance of weak noncovalent interaction between side chains (in addition to the hydrogen-bond and aromatic interactions) to stabilise supramolecular self-assembly of Fmoc-functionalised compounds. The current observations provide a lead to the design of new sulfur-based low molecular weight gelators for various potential applications.