Nanofibrillated Cellulose Hydrogels Research Articles

Robotically 3D printed architectural membranes from ambient dried cellulose nanofibril-alginate hydrogel

Cellulose nanofibril hydrogel mixed with an aqueous solution of sodium alginate is a novel bio-based material suitable for 3D printing of lightweight membranes with exquisite properties and sustainable traits. However, fundamental knowledge enabling its applications in architectural design is still missing. Hence, this study examines the macro-scale features of lightweight membranes from cellulose nanofibril-alginate hydrogel, relevant for the design of various interior architectural products, such as wall claddings, ceiling tiles, room partitions, tapestries, and window screens. Through iterative prototyping experiments involving robotic 3D printing of lightweight membranes, their upscaling potential is demonstrated. Correlations between toolpath designs and shrinkages are also characterized, alongside an in-depth analysis of coloration changes upon ambient drying. Further, the tunability potential of various architectural features, enabled by bespoke 3D printing toolpath design, is discussed and exemplified. The aim is to expose the wide palette of design possibilities for cellulose nanofibril-alginate membranes, encompassing variations in curvature, porosity, translucency, texture, patterning, pliability, and feature sizes. The results comprise an important knowledge foundation for the design and manufacturing of custom lightweight architectural products from cellulose nanofibril-alginate hydrogel. These products could be applied in a variety of new bio-based, sustainable interior building systems, replacing environmentally harmful, fossil-based solutions.

318.6: Nanofibrillated cellulose hydrogel with stem cells, organoids and wound care

318.6: Nanofibrillated cellulose hydrogel with stem cells, organoids and wound care

Photocross-Linkable and Shape-Memory Biomaterial Hydrogel Based on Methacrylated Cellulose Nanofibres.

In the context of three-dimensional (3D) cell culture and tissue engineering, 3D printing is a powerful tool for customizing in vitro 3D cell culture models that are critical for understanding the cell-matrix and cell-cell interactions. Cellulose nanofibril (CNF) hydrogels are emerging in constructing scaffolds able to imitate tissue in a microenvironment. A direct modification of the methacryloyl (MA) group onto CNF is an appealing approach to synthesize photocross-linkable building blocks in formulating CNF-based bioinks for light-assisted 3D printing; however, it faces the challenge of the low efficiency of heterogenous surface modification. Here, a multistep approach yields CNF methacrylate (CNF-MA) with a decent degree of substitution while maintaining a highly dispersible CNF hydrogel, and CNF-MA is further formulated and copolymerized with monomeric acrylamide (AA) to form a super transparent hydrogel with tuneable mechanical strength (compression modulus, approximately 5-15 kPa). The resulting photocurable hydrogel shows good printability in direct ink writing and good cytocompatibility with HeLa and human dermal fibroblast cell lines. Moreover, the hydrogel reswells in water and expands to all directions to restore its original dimension after being air-dried, with further enhanced mechanical properties, for example, Young's modulus of a 1.1% CNF-MA/1% PAA hydrogel after reswelling in water increases to 10.3 kPa from 5.5 kPa.

Tuning the water interactions of cellulose nanofibril hydrogels using willow bark extract

Cellulose nanofibrils (CNFs) are increasingly used as precursors for foams, films and composites, where water interactions are of great importance. In this study, we used willow bark extract (WBE), an underrated natural source of bioactive phenolic compounds, as a plant-based modifier for CNF hydrogels, without compromising their mechanical properties. We found that the introduction of WBE into both native, mechanically fibrillated CNFs and TEMPO-oxidized CNFs increased considerably the storage modulus of the hydrogels and reduced their swelling ratio in water up to 5–7 times. A detailed chemical analysis revealed that WBE is composed of several phenolic compounds in addition to potassium salts. Whereas the salt ions reduced the repulsion between fibrils and created denser CNF networks, the phenolic compounds - which adsorbed readily on the cellulose surfaces - played an important role in assisting the flowability of the hydrogels at high shear strains by reducing the flocculation tendency, often observed in pure and salt-containing CNFs, and contributed to the structural integrity of the CNF network in aqueous environment. Surprisingly, the willow bark extract exhibited hemolysis activity, which highlights the importance of more thorough investigations of biocompatibility of natural materials. WBE shows great potential for managing the water interactions of CNF-based products.

Shape-recovering nanocellulose networks: Preparation, characterization and modeling

Development of strong cellulose nanofibril (CNF) networks for advanced applications, such as in the biomedical field, is of high importance owing to the biocompatible nature and plant-based origin of cellulose nanofibrils. Nevertheless, lack of mechanical strength and complex synthesis methods hinder the application of these materials in areas where both toughness and manufacturing simplicity are required. In this work, we introduce a facile method for the synthesis of a low solid content (< 2 wt%), covalently crosslinked CNF hydrogel where Poly (N-isopropylacrylamide) (NIPAM) chains are utilized as crosslinks between the nanofibrils. The resulting networks have the capability to fully recover the shape in which they were formed after various drying and rewetting cycles. Characterization of the hydrogel and its constitutive components was performed using X-ray scattering, rheological investigations and uniaxial testing in compression. Influence of covalent crosslinks was compared with networks crosslinked by the addition of CaCl2. Among other things the results show that the mechanical properties of the hydrogels can be tuned by controlling the ionic strength of the surrounding medium. Finally, a mathematical model was developed based on the experimental results, which describes and predicts to a decent degree the large-deformation, elastoplastic behavior, and fracture of these networks.

Electrochemically synthesized graphene/TEMPO-oxidized cellulose nanofibrils hydrogels: Highly conductive green inks for 3D printing of robust structured EMI shielding aerogels

We report on the design and synthesis of bio-based, electrically conductive green inks for direct ink writing (DIW) of lightweight electronics and electromagnetic interference (EMI) shields. The inks incorporate fibrillated cellulose and electrochemically synthesized graphene oxide (EGO), with no production and/or consumption of hazardous chemicals. The cellulosic component, TOCNF ((2,2,6,6-tetrame-thylpiperidin-1-yl) oxidanyl (TEMPO)-oxidized cellulose nanofibrils), improves the colloidal dispersion and the rheological properties of EGO-based inks for high-resolution 3D printing via DIW. The printing fidelity and shape retention significantly rely on the EGO/TOCNF loading and ratio in the precursor hydrogel inks. Aerogels result from freeze drying, allowing the production of 3D ultra-lightweight materials with prescribed macro-scale design featuring excellent stability and ease of handling. It is shown that the nano- and micro-scale design of the aerogels can be readily tuned by the solid content and EGO/TOCNF ratio in the inks. This multi-scale materials design provides a unique opportunity to control the mechanical and electrical properties of the printed structures. For instance, aerogels with compression modulus in the range of 250–1096 kPa are obtained based on the composition of the inks. For the optimized ink, an excellent EMI shielding effectiveness, as high as 55.6 dB, is achieved.

Stiffness-Controlled Hydrogels for 3D Cell Culture Models.

Nanofibrillated cellulose (NFC) hydrogel is a versatile biomaterial suitable, for example, for three-dimensional (3D) cell spheroid culturing, drug delivery, and wound treatment. By freeze-drying NFC hydrogel, highly porous NFC structures can be manufactured. We freeze-dried NFC hydrogel and subsequently reconstituted the samples into a variety of concentrations of NFC fibers, which resulted in different stiffness of the material, i.e., different mechanical cues. After the successful freeze-drying and reconstitution, we showed that freeze-dried NFC hydrogel can be used for one-step 3D cell spheroid culturing of primary mesenchymal stem/stromal cells, prostate cancer cells (PC3), and hepatocellular carcinoma cells (HepG2). No difference was observed in the viability or morphology between the 3D cell spheroids cultured in the freeze-dried and reconstituted NFC hydrogel and fresh NFC hydrogel. Furthermore, the 3D cultured spheroids showed stable metabolic activity and nearly 100% viability. Finally, we applied a convolutional neural network (CNN)-based automatic nuclei segmentation approach to automatically segment individual cells of 3D cultured PC3 and HepG2 spheroids. These results provide an application to culture 3D cell spheroids more readily with the NFC hydrogel and a step towards automatization of 3D cell culturing and analysis.

Probing metal-carboxylate interactions in cellulose nanofibrils-based hydrogels using nonlinear oscillatory rheology

Cellulose nanofibrils (CNFs) have gained much attention as part of biocompatible soft hydrogels used in various biomedical applications such as biodegradable scaffolds, biomedicine, tissues, and regenerative medicine. The CNF hydrogels were mediated with metal cations for improved mechanical strength and structural reversibility. Intermolecular interactions in these CNF hydrogels are controlled by metal cation-carboxylate coordination bonding, leading to the creation of interconnected three-dimensional nanofibril structures that produce high structural reversibility. The nonlinear inter- and intra-cycle were investigated viscoelastic responses of these CNF hydrogels by quantitative nonlinear viscoelastic parameters and transient responses. The dynamic and transitional analyses conducted indicate that the structural deformation and recovery characteristics of the CNF hydrogels are affected by the valency number of the metal cations. This property can be carefully chosen to tune the intermolecular interactions between the cellulose nanofibrils to create an efficient interwoven network structure with high structural reversibility that can go through repeated cycles of reformation and yielding.

Angiogenic Potential of Human Adipose-Derived Mesenchymal Stromal Cells in Nanofibrillated Cellulose Hydrogel.

Adipose-derived mesenchymal stromal cells (ASCs) hold great potential for cellular therapies by having immunomodulatory behavior and tissue regenerative properties. Due to the capability of ASCs to differentiate into endothelial cells (ECs) and other angiogenic cell types, such as pericytes, ASCs are a highly valuable source for stimulating angiogenesis. However, cellular therapies in tissue engineering have faced challenges in poor survival of the cells after transplantation, which is why a protective biomaterial scaffold is required. In this work, we studied the potential of nanofibrillated cellulose (NFC) hydrogel to be utilized as a suitable matrix for three-dimensional (3D) cell culturing of human-derived ASCs (hASCs) and studied their angiogenic properties and differentiation potential in ECs and pericytes. In addition, we tested the effect of hASC-conditioned medium and stimulation with angiopoietin-1 (Ang-1) on human umbilical vein endothelial cells (HUVECs) to induce blood vessel-type tube formation in NFC hydrogel. The hASCs were successfully 3D cell cultured in NFC hydrogel as they formed spheroids and had high cell viability with angiogenic features. Most importantly, they showed angiogenic potential by having pericyte-like characteristics when differentiated in EC medium, and their conditioned medium improved HUVEC viability and tube formation, which recalls the active paracrine properties. This study recommends NFC hydrogel for future use as an animal-free biomaterial scaffold for hASCs in therapeutic angiogenesis and other cell therapy purposes.

Elongational behaviour of electrostatically stabilised and concentrated CNF and CNC hydrogels: Experiments and modelling

TEMPO-oxidized cellulose nanofibril (CNF) hydrogels or cellulose nanocrystal (CNC) hydrogels can now be obtained at high concentrations (>10 wt%) and used to fabricate biobased materials and structures. Thus, it is required to control and model their rheology in process-induced multiaxial flow conditions using 3D tensorial models. For that purpose, it is necessary to investigate their elongational rheology. Thus, concentrated TEMPO-oxidized CNF and CNC hydrogels were subjected to monotonic and cyclic lubricated compression tests. These tests revealed for the first time that the complex compression rheology of these two electrostatically stabilised hydrogels combines viscoelasticity and viscoplasticity. The effect of their nanofibre content and aspect ratio on their compression response was clearly emphasised and discussed. The ability of a non-linear elasto-viscoplastic model to reproduce the experiments was assessed. Even if some discrepancies were observed at low or high strain rates, the model was consistent with the experiments.

Injectable self-healing nanocellulose hydrogels crosslinked by aluminum: Cellulose nanocrystals vs. cellulose nanofibrils

• Three types of hydrogels were successfully constructed from nanocellulose. • Aluminum ion was applied as crosslinker to reinforce the hydrogels. • The properties of the hydrogels were compared and summarized in a radar chart. • Cellulose nanocrystals hydrogels showed stronger water holding capacity. • Cellulose nanofibrils hydrogels had higher hardness and stronger antidegradation. With excellent biocompatibility and unique physiochemical properties, nanocelluloses including cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs) are promising candidates for preparing biomedical hydrogels. CNCs and CNFs are different in morphology and surface charges. Herein, CNCs and two CNFs (CNFs-C, Carboxylated CNFs; CNFs-P, Phosphorylated CNFs) were synthesized and applied to fabricate hydrogels through metal crosslinking. Aluminum crosslinking was found to be the best choice for enhancing the strength. This study systematically compared the morphologies, storage modulus, loss factor, continuous shear ramp, self-healing, swelling, in vitro degradation and injectable properties of the fabricated hydrogels. Further, a radar chart is summarized as guidelines to direct the rational selection to meet the specific requirements of further biomedical applications. At the same nanocellulose concentration and after Al 3+ crosslinking, CNCs hydrogels had strong water holding capacity twice as much as that of CNFs hydrogels. While CNFs hydrogels showed higher hardness and stronger resistance to degradation than that of CNCs. These results provide detailed insights into nanocellulose hydrogels, making it possible to use these guidelines to select hydrogels for desired performance.

Physical, Rheological and Mechanical Properties of Alkali Activated Hydrogels Based on Nanofibrillated Cellulose

ABSTRACT Hydrogels are classified as a three-dimensional network system, capable of retaining large amounts of water while preserving their shape and dimensional stability. Due to their natural origin and biocompatibility with human tissue, cellulose nanofibrils are often considered to be promising candidates for bioactive hydrogels preparation. For such applications, their responsiveness under different types of mechanical load, including multiple cyclic compressions, is of crucial importance. In the present study, cellulose nanofibril-based hydrogels were initiated though a simple alkali neutralization treatment. Structural, rheological and compressive features were investigated as a function of elevated NaOH concentration and physical gelling conditions. It was found that a sufficiently concentrated alkaline solution allows the formation of mechanically robust cellulose nanofibril hydrogels, which can be dried to the state of ultralight material, aerogel, of low density (0.057 g cm −3), superior porosity (96.2%), super water absorbant capacity (1200%), and exceptional shear and compressive load resilience with elasticity modulus of 9.3 kPa. These outstanding characteristics can be predominantly attributed to the polymorphic conversion of cellulose I to cellulose II, which results from the mercerization of cellulose nanofibrils and creates a stable and firm hydrogels texture.

Preparation of methylated TEMPO-oxidized cellulose nanofibril hydrogel with high-temperature sensitivity

Preparation of methylated TEMPO-oxidized cellulose nanofibril hydrogel with high-temperature sensitivity

Rheology of concentrated and highly concentrated enzymatic cellulose nanofibril hydrogels during lubricated compression

Processing cellulose nanofibril (CNF) hydrogels with a high concentration is a solution to reduce logistics costs and drying energy and to produce CNF-based materials with good dimensional stability. However, the rheology of concentrated and highly concentrated CNF hydrogels is poorly understood due to the difficulties to characterise them using standard shear rheometers. In this study, enzymatic CNF hydrogels in the concentrated and highly concentrated regimes (3–13.6 wt%) were subjected to lubricated compression at various strain rates. At low strains, compression curves exhibited a linear regime. At higher strains and low strain rates, a heterogeneous and marked hardening of stress levels was observed and accompanied with a two-phase flow with significant fluid segregation and network consolidation. At high strain rates, a homogeneous and incompressible one-phase plateau-like regime progressively established. In this regime, a yield stress was measured and compared with literature data, showing a good agreement with them.

Preparation of green magnetic hydrogel from cellulose nanofibril (CNF) originated from soybean residue for effective and rapid removal of copper ions from waste water

At present, people are paying more and more attention to the development of sustainable biological materials. In this study, green magnetic hydrogel was prepared by blending Soybean residue cellulose nanofibrils (CNF)，poly (vinyl alcohol), diatomite and nano-Fe3O4 for Cu2+ removal. Results showed that the decrease of CNF diameter improved the mechanical property and swelling of the magnetic CNF hydrogel (the maximum tensile strength was 2.3Mpa) for better Cu2+ adsorption. Adsorption studies displayed that the adsorption of Cu2+ followed the pseudo-second-order kinetic model, and the adsorption process is mainly chemical adsorption. This work provided a feasible method to fabricate magnetic hydrogel from green renewable resource as a new and promising adsorbent.

Polydopamine-Modified Cellulose Nanofibril Composite Aerogel: An Effective Dye Adsorbent.

In this study, a new cellulose nanofibril (CNF) composite aerogel was fabricated using a green and facile mussel-inspired coating strategy. First, the CNF hydrogel was crosslinked by calcium ion followed by immersion in dopamine solution. Second, the surface of CNF was modified using polydopamine (PDA) to obtain PDA@CNF (PCNF) composite aerogel. The PCNF composite aerogels had large surface areas (368.15 m2/g) and low bulk density (27.2 mg/cm3). The composite aerogel exhibited improved mechanical properties, which were almost three times compared with those of CNF aerogel. Moreover, PCNF composite aerogel had good resilience under a wet state. The PDA functional layer remarkably enhanced the adsorption capacities of the composite aerogel for methylene blue (MB). The maximum adsorption of MB was 208 mg/g at an initial dye concentration of 50 mg/L. The adsorption isotherm and kinetic behaviors of the composite aerogel were consistent with Langmuir and pseudo-second-order models. In addition, the PCNF composite aerogels had a high adsorption capacity over a wide pH range. The reuse experiment showed that the removal efficiency of the composite aerogel remained higher than 85% after five cycles. Therefore, PCNF composite aerogels may have potential application in wastewater treatment due to its environmental sustainability and low energy consumption.

Fluorescent carbon dots crosslinked cellulose Nanofibril/Chitosan interpenetrating hydrogel system for sensitive detection and efficient adsorption of Cu (II) and Cr (VI)

• One-pot synthesis of carbon dots cross-linked cellulose nanofibril hydrogel. • The introduction of chitosan by solvent displacement forms IPN hydrogel. • Carbon dots provide visual detection during Cu (II) and Cr (VI) adsorption. • Amphoteric biomass and carbon dots provide adsorption sites for Cu (II) and Cr (VI). • The mechanism of Cu (II) and Cr (VI) sorption and sensing was determined. To address the pollution of heavy metal ions in water resources, a novel self-assembled nitrogen-doped carbon dots (NCDs) crosslinked, cellulose nanofibril (CNF) and chitosan (CS) based interpenetrating polymer network (IPN) hydrogel (NCDs-CNF/CSgel) was prepared for simultaneous fluorescent detection and adsorption of Cu (II) cation and Cr (VI) anion. The NCDs cross-linked CNF hydrogel network was synthesized by an environmentally friendly low-temperature hydrothermal process and subsequently, solvent replacement was used to form the second layer of CS network. The morphology, chemical structure, fluorescent properties, and adsorption behaviors of NCDs-CNF/CSgel were analyzed. The results showed that NCDs-CNF/CSgel exhibited a wide linear range of fluorescence response for Cu (II) (50–1000 mg/L, detection limit of 40.3398 mg/L) and superior sensitivity and selectivity of fluorescence response for Cr (VI) (linear range of 1–50 mg/L, detection limit of 0.7093 mg/L). NCDs-CNF/CSgel showed high adsorption capacities of 148.30 mg/g and 294.46 mg/g for Cu (II) and Cr (VI), respectively, and fitted well to the pseudo-second-order model and the Langmuir model. The detection of Cu (II) and Cr (VI) and their adsorption mechanisms onto NCDs-CNF/CSgel were further determined. Hence, this work provides a green and sustainable approach for the synthesis of a functional material which can be applied for the detection and adsorption of heavy metal ions.

Synthesis of metal–organic-frameworks on polydopamine modified cellulose nanofibril hydrogels: constructing versatile vehicles for hydrophobic drug delivery

Synthesis of metal–organic-frameworks on polydopamine modified cellulose nanofibril hydrogels: constructing versatile vehicles for hydrophobic drug delivery

Molecular Insights on Successful Reconstitution of Freeze-Dried Nanofibrillated Cellulose Hydrogel.

The diversity and safety of nanofibrillated cellulose (NFC) hydrogels have gained a vast amount of interest at the pharmaceutical site in recent years. Moreover, this biomaterial has a high potential to be utilized as a protective matrix during the freeze-drying of heat-sensitive pharmaceuticals and biologics to increase their properties for long-term storing at room temperature and transportation. Since freeze-drying and subsequent reconstitution have not been optimized for this biomaterial, we must find a wider understanding of the process itself as well as the molecular level interactions between the NFC hydrogel and the most suitable lyoprotectants. Herein we optimized the reconstitution of the freeze-dried NFC hydrogel by considering critical quality attributes required to ensure the success of the process and gained insights of the obtained experimental data by simulating the effects of the used lyoprotectants on water and NFC. We discovered the correlation between the measured characteristics and molecular dynamics simulations and obtained successful freeze-drying and subsequent reconstitution of NFC hydrogel with the presence of 300 mM of sucrose. These findings demonstrated the possibility of using the simulations together with the experimental measurements to obtain a more comprehensive way to design a successful freeze-drying process, which could be utilized in future pharmaceutical applications.

Drug diffusivities in nanofibrillar cellulose hydrogel by combined time-resolved Raman and fluorescence spectroscopy

Hydrogels, natural and synthetic origin, are actively studied for their use for implants and payload carriers. These biomaterials for delivery systems have enormous potential in basic biomedical research, drug development, and long-term delivery of biologics. Nanofibrillated cellulose (NFC) hydrogels, both natural and anionic (ANFC) ones, allow drug loading for immediate and controlled release via the slow drug dissolution of solid drug crystals into hydrogel and its subsequent release. This property makes NFC originated hydrogels an interesting non-toxic and non-human origin material as drug reservoir for long-term controlled release formulation or implant for patient care. A compelling tool for studying NFC hydrogels is Raman spectroscopy, which enables to resolve the chemical structures of different molecules in a high-water content like hydrogels, since Raman spectroscopy is insensitive to water molecules. That offers real time investigation of label-free drugs and their release in high-water-content media. Despite the huge potential of Raman spectroscopy in bio-pharmaceutical applications, the strong fluorescence background of many drug samples masking the faint Raman signal has restricted the widespread use of it. In this study we used a Raman spectrometer capable of suppressing the unpleasant fluorescence background by combining a pulsed laser and time-resolved complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diode (SPAD) line sensor for the label-free investigation of Metronidazole and Vitamin C diffusivities in ANFC. The results show the possibility to modulate the ANFC-based implants and drug delivery systems, when the release rate needs to be set to a desired value. More importantly, the now developed label free real-time method is universal and can be adapted to any hydrogel/drug combination for producing reliable drug diffusion coefficient data in complex and heterogeneous systems, where traditional sampling-based methods are cumbersome to use. The wide temporal range of the time-resolved CMOS SPAD sensors makes it possible to capture also the fluorescence decay of samples, giving rise to a combined time-resolved Raman and fluorescence spectroscopy, which provides additional information on the chemical, functional and structural changes in samples.