Nanocellulosic materials, such as cellulose nanocrystals, cellulose nanofibers, and bacterial nanocellulose, that display high surface area, mechanical strength, biodegradability, and tunable surface chemistry have attracted great attention over the last decade for biomedical applications. Simultaneously, 3D printing is revolutionizing the field of biomedical engineering, which enables the fast and on-demand printing of customizable scaffolds, tissues, and organs. Nanocellulosic materials hold tremendous potential for 3D bioprinting due to their printability, their shear thinning behavior, their ability to live cell support and owing to their excellent biocompatibility. The amalgamation of nanocellulose-based feedstocks and 3D bioprinting is therefore of critical interest for the development of advanced functional 3D hydrogels. In this context, this review briefly discusses the most recent key developments and challenges in 3D bioprinting nanocellulose-based hydrogel constructs that have been successfully tested for mammalian cell viability and used in tissue engineering applications.
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.
The current perspective presents an outlook on developing gut-like bioreactors with immobilized probiotic bacteria using cellulose hydrogels. The innovative concept of using hydrogels to simulate the human gut environment by generating and maintaining pH and oxygen gradients in the gut-like bioreactors is discussed. Fundamentally, this approach presents novel methods of production as well as delivery of multiple strains of probiotics using bioreactors. The relevant existing synthesis methods of cellulose hydrogels are discussed for producing porous hydrogels. Harvesting methods of multiple strains are discussed in the context of encapsulation of probiotic bacteria immobilized on cellulose hydrogels. Furthermore, we also discuss recent advances in using cellulose hydrogels for encapsulation of probiotic bacteria. This perspective also highlights the mechanism of probiotic protection by cellulose hydrogels. Such novel gut-like hydrogel bioreactors will have the potential to simulate the human gut ecosystem in the laboratory and stimulate new research on gut microbiota.
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