Active Principal Ingredient (API) encapsulation through adsorption and physical entrapment onto TEMPO-oxidized cellulose nanofibrils (toCNFs) is possible, but challenges such as burst release and use of low water-soluble API such as sulfadiazine (SD) are yet to be addressed. The objective of this study is to assess the release property and antibacterial activity of toCNF/β-Cyclodextrin (β-CD)/SD materials in the form of films. Release in sink conditions was achieved with result highlighting the importance of the toCNF network structure, which is tightened at acidic pH for toCNFs due to its carboxylic content, reducing the burst effect phenomena. Antibacterial activity against Staphylococcus aureus and Escherichia coli was assessed and the results showed a clear beneficial impact of using β-CDs. An antibacterial effect for toCNF/SD films is confirmed for 3 successive applications whereas an antibacterial effect for a toCNF/CMβCD/SD film is prolonged up to 7 successive applications. The improvement of the topical release of a prophylactic agent with these materials are making them promising for biomedical applications such as wound dressing. Graphic abstract: [Figure not available: see fulltext.] © 2023, The Author(s)

Cellulose nanofibrils (CNFs) are multiscale hydrophilic biocompatible polysaccharide materials derived from wood and plants. TEMPO-mediated oxidation of CNFs (TO-CNF) turns some of the primary hydroxyl groups to carboxylate and aldehyde groups. Unlike carboxylic functional groups, there is little or no information about the biological role of the aldehyde groups on the surface of wood-based CNFs. In this work, we replaced the aldehyde groups in the TO-CNF samples with carboxyl groups by another oxidation treatment (TO-O-CNF) or with primary alcohols with terminal hydroxyl groups by a reduction reaction (TO-R-CNF). Rat mesenchymal stem/stromal cells (MSCs) derived from bone marrow were seeded on polystyrene tissue culture plates (TCP) coated with CNFs with and without aldehyde groups. TCP and TCP coated with bacterial nanocellulose (BNC) were used as control groups. Protein adsorption measurements demonstrated that more proteins were adsorbed from cell culture media on all CNF surfaces compared to BNC. Live/dead and lactate dehydrogenase assays confirmed that all nanocellulose biomaterials supported excellent cell viability. Interestingly, TO-R-CNF samples, which have no aldehyde groups, showed better cell spreading than BNC and comparable results to TCP. Unlike TO-O-CNF surfaces, which have no aldehyde groups either, TO-R-CNF stimulated cells, in osteogenic medium, to have higher alkaline phosphatase activity and to form more biomineralization than TCP and TO-CNF groups. These findings indicate that the presence of aldehyde groups (280 ± 14 μmol/g) on the surface of TEMPO-oxidized CNFs might have little or no effect on attachment, proliferation, and osteogenic differentiation of MSCs. © 2023 The Authors.

In this work, we aimed to tune cellulose nanocrystals (CNCs) properties by introducing different functional groups (aldehyde, carboxyl, silane, and ammonium groups) on the surface through different chemical modifications. These functional groups were obtained by combining: the periodate oxidation with TEMPO-oxidation, aminosylation or cationization. CNCs produced and their films were characterized to elucidate their performances. The results showed that the properties of obtained CNCs varied depending on the grafted functionalities on the surface. The results reveal that after each modification a colloidal stability is preserved. Interestingly, Periodate oxidation of cellulose nanocrystals results in film components that interact through intra- and intermolecular hemiacetals and lead to films with a tensile strength of 116 MPa compared to the pristine CNCs, in contrast the subsequent modifications led to lower tensile strength. Of note, remarkable thermal stability has been achieved after modifications reaching a maximum of 280 °C. The oxygen barrier properties of the films after modifications varied between 0.48 and 0.54 cm3μm/(m2d*kPa) at 50 % RH. 

β-Cyclodextrin (β-CD) and its derivatives are cyclic oligosaccharides which present the ability to form inclusion complexes with hydrophobic molecules and can bring new functionalities to a wide range of materials. As of today, the most used prophylactic drugs for wound dressing applications are sulfadiazine (SD) and its derivatives silver sulfadiazine (SSD). These drugs are used to prevent infections of the wounds; however, their low intrinsic water-solubility is a hindrance to their use. In this study, the inclusion complex formation between SD/SSD and the various β-CDs were assessed with various protocols. Isothermal Titration Calorimetry (ITC) experiments led to the conclusion that the formation constants measured for SD and SSD are sufficiently similar meaning that SD can be considered as a satisfactory model molecule. Phase Solubility Diagram (PSD) were built for SD and the various β-CDs, highlighting a 1:1 stoichiometry of inclusion and a linear increase in solubility of SD with increasing concentration of β-CDs- The formation constant ranged from 197 M−1 to 245 M−1 for the different β-CDs. X-Ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) experiments revealed the different physico-chemical properties affected by the formation of an inclusion complex. Finally, Nuclear Magnetic Resonance (NMR) experiments confirmed the depth of penetration of SD inside the β-CDs cavity as well as the orientation of SD, highlighting the fact that CM-β-CDs induce a deeper penetration than other β-CDs.

Cellulose nanofibrils, CNFs, show great potential in many application areas. One main aspect limiting the industrial use is the slow and energy demanding dewatering of CNF suspensions. Here we investigate the dewatering with a piston press process. Three different CNF grades were dewatered to solid contents between approx. 20 and 30%. The CNF grades varied in charge density (30, 106 and 604 µmol/g) and fibrillation degree. The chemical conditions were varied by changing salt concentration (NaCl) and pH and the dewatering rates were compared before and after these changes. For the original suspensions, a higher charge provides slower dewatering with the substantially slowest dewatering for the highest charged CNFs. However, by changing the conditions it dewatered as fast as the two lower charged CNFs, even though the salt/acid additions also improved the dewatering rate for these two CNFs. Finally, by tuning the conditions, fast dewatering could be obtained with only minor effect on film properties (strength and oxygen barrier) produced from redispersed dispersion. However, dewatering gives some reduction in viscosity of the redispersed dispersions. This may be a disadvantage if the CNF application is as e.g. rheology modifier or emulsion stabilizer. Graphical abstract: [Figure not available: see fulltext.].

TEMPO-Oxidized cellulose nanofibrils (toCNF), in the form of highly entangled network such as membrane or cryogels, have proven to be of interest for various applications, including drug release or purification by pollutant adsorption. β-Cyclodextrins (β-CDs) have the ability to form inclusion complexes with large amount of hydrophobic molecules, and are considered as a promising way to bring new functionalities to these materials, by reducing drug burst release effect or improving the pollutant adsorption properties. The study of the adsorption β-CDs onto toCNF is then crucial to design toCNF/β-CDs materials, but is very complex due to the chemical proximity between these compounds. In this study, we develop toCNF cryogels containing various types of β-CDs derivatives by physical adsorption. Different protocols for analyzing the interactions between these compounds, such as Isothermal Titration Calorimetry (ITC), Quartz-Crystal Microbalance with dissipation monitoring (QCM-d) and a Phenolphthalein-based protocol (PhP protocol) have been performed. Adsorption between β-CD and toCNF was proven at two different temperatures with ITC. QCM-d measurements allowed measuring adsorption of different β-CDs derivatives onto toCNF, with higher adsorption measured for the modified β-CDs, and with estimated binding capacity ranging from 13.4 to 47.6 μmol/g toCNF. PhP protocol allowed us to monitor the amount of β-CDs released in aqueous environment, highlighting a lower release for modified β-CDs onto toCNF, and the results were consistent with the estimated binding capacity. This quantification of the binding adsorption capacity of various β-CDs is key results for optimizing the design of toCNF/β-CDs materials.

Cellulose nanofibrils (CNFs) were obtained by applying a chemical pretreatment consisting of autoclaving the pulp fibers in sodium hydroxide, combined with 2,2,6,6-tetramethylpiperidinyl-1-oxyl-mediated oxidation. Three levels of sodium hypochlorite were applied (2.5, 3.8, and 6.0 mmol/g) to obtain CNF qualities (CNF_2.5, CNF_3.8, and CNF_6.0) with varying content of carboxyl groups, that is, 1036, 1285, and 1593 μmol/g cellulose. The cytotoxicity and skin irritation potential (indirect tests) of the CNFs were determined according to standardized in vitro testing for medical devices. We here demonstrate that autoclaving (121 °C, 20 min), which was used to sterilize the gels, caused a modification of the CNF characteristics. This was confirmed by a reduction in the viscosity of the gels, a morphological change of the nanofibrils, by an increase of the ultraviolet-visible absorbance maxima at 250 nm, reduction of the absolute zeta potential, and by an increase in aldehyde content and reducing sugars after autoclaving. Fourier-transform infrared spectroscopy and wide-angle X-ray scattering complemented an extensive characterization of the CNF gels, before and after autoclaving. The antibacterial properties of autoclaved carboxylated CNFs were demonstrated in vitro (bacterial survival and swimming assays) on Pseudomonas aeruginosa and Staphylococcus aureus. Importantly, a mouse in vivo surgical-site infection model on S. aureus revealed that CNF_3.8 showed pronounced antibacterial effect and performed as good as the antiseptic Prontosan wound gel.

Photopolymerization is an effective method to covalently cross-link polymer chains that can be shaped into several biomedical products and devices. Additionally, polymerization reaction may induce a fluid-solid phase transformation under physiological conditions and is ideal for in vivo cross-linking of injectable polymers. The photoinitiator is a key ingredient able to absorb the energy at a specific light wavelength and create radicals that convert the liquid monomer solution into polymers. The combination of photopolymerizable polymers, containing appropriate photoinitiators, and effective curing based on dedicated light sources offers the possibility to implement photopolymerization technology in 3D bioprinting systems. Hence, cell-laden structures with high cell viability and proliferation, high accuracy in production, and good control of scaffold geometry can be biofabricated. In this review, we provide an overview of photopolymerization technology, focusing our efforts on natural polymers, the chemistry involved, and their combination with appropriate photoinitiators to be used within 3D bioprinting and manufacturing of biomedical devices. The reviewed articles showed the impact of different factors that influence the success of the photopolymerization process and the final properties of the cross-linked materials.

Cellulose nanocrystals (CNCs) and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)- oxidized cellulose nanofibrils (T-CNFs) were tested as enhanced oil recovery (EOR) agents through core floods and microfluidic experiments. Both particles were mixed with low salinity water (LSW). The core floods were grouped into three parts based on the research objectives. In Part 1, secondary core flood using CNCs was compared to regular water flooding at fixed conditions, by reusing the same core plug to maintain the same pore structure. CNCs produced 5.8% of original oil in place (OOIP) more oil than LSW. For Part 2, the effect of injection scheme, temperature, and rock wettability was investigated using CNCs. The same trend was observed for the secondary floods, with CNCs performing better than their parallel experiment using LSW. Furthermore, the particles seemed to perform better under mixed-wet conditions. Additional oil (2.9–15.7% of OOIP) was produced when CNCs were injected as a tertiary EOR agent, with more incremental oil produced at high temperature. In the final part, the effect of particle type was studied. T-CNFs produced significantly more oil compared to CNCs. However, the injection of T-CNF particles resulted in a steep increase in pressure, which never stabilized. Furthermore, a filter cake was observed at the core face after the experiment was completed. Microfluidic experiments showed that both T-CNF and CNC nanofluids led to a better sweep efficiency compared to low salinity water flooding. T- CNF particles showed the ability to enhance the oil recovery by breaking up events and reducing the trapping efficiency of the porous medium. A higher flow rate resulted in lower oil recovery factors and higher remaining oil connectivity. Contact angle and interfacial tension measurements were conducted to understand the oil recovery mechanisms. CNCs altered the interfacial tension the most, while T-CNFs had the largest effect on the contact angle. However, the changes were not significant enough for them to be considered primary EOR mechanisms.

Many studies show how biomaterial properties like stiffness, mechanical stimulation and surface topography can influence cellular functions and direct stem cell differentiation. In this work, two different natural materials, gelatin (Gel) and cellulose nanofibrils (CNFs), were combined to design suitable 3D porous biocomposites for soft-tissue engineering. Gel was selected for its well-assessed high biomimicry that it shares with collagen, from which it derives, while the CNFs were chosen as structural reinforcement because of their exceptional mechanical properties and biocompatibility. Three different compositions of Gel and CNFs, i.e., with weight ratios of 75:25, 50:50 and 25:75, were studied. The biocomposites were morphologically characterized and their total-and macro-porosity assessed, proving their suitability for cell colonization. In general, the pores were larger and more isotropic in the biocomposites compared to the pure materials. The influence of freeze-casting and dehydrothermal treatment (DHT) on mechanical properties, the absorption ability and the shape retention were evaluated. Higher content of CNFs gave higher swelling, and this was attributed to the pore structure. Cross-linking between CNFs and Gel using DHT was confirmed. The Young’s modulus increased significantly by adding the CNFs to Gel with a linear relationship with respect to the CNF amounts. Finally, the biocomposites were characterized in vitro by testing cell colonization and growth through a quantitative cell viability analysis performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, the cell viability analysis was performed by the means of a Live/Dead test with Human mesenchymal stem cells (hMSCs). All the biocomposites had higher cytocompatibility compared to the pure materials, Gel and CNFs. © 2020 by the authors.