Micropatterned Hydrogels with Highly Ordered Cellulose Nanocrystals for Visually Monitoring Cardiomyocytes.

Cardiac microphysiological systems are accurate in vitro platforms that reveal the biological mechanisms underlying cardiopathy, accelerating pharmaceutical research in this field. Current cardiac microphysiological devices and organs-on-chips consist of several layers prepared with complex, multi-step processes. Incorporating inorganic photonic crystals may cause long-term biocompatibility issues. Herein, micropatterned hydrogels with anisotropic structural colors are prepared by locking shear-oriented tunicate cellulose nanocrystals (TCNCs) in hydrogel networks through in situ polymerization, allowing the visualization and monitoring of cardiomyocytes. The anisotropic hydrogels are composed of highly ordered TCNCs with bright interference color and micro-grooved methacrylated gelatin with excellent biocompatibility. The microgroove patterns induce cardiomyocyte alignment and the autonomous beating of cardiomyocytes causes the hydrogels to deform, dynamically shifting the interference color. These micropatterned hydrogels could noninvasively monitor real-time changes of cardiomyocytes under pharmaceutical treatment and electrical stimulation through wavelength shifts in the transmittance spectra. This system provides a new way to detect the beat rate of cardiac tissue and it may contribute to high throughput develop.

Synthesis and Fluorescent Thermoresponsive Properties of Tetraphenylethylene-Labeled Methylcellulose.

Functional polymer, especially the one based on renewable and sustainable materials, has attracted increasing attention to satisfy the growing demand for the design of stimuli-responsive devices. Methylcellulose (MC) is a water-soluble derivative of cellulose, which has been widely used in many fields for its biocompatibility and biological inertness. In this work, MC is labeled by tetraphenylethylene (TPE) via azide-alkyne click reaction to obtain a fluorescent cellulose-based derivative of MC-TPE. The degree of substitution of MC-TPE is determined to be 0.074, which can be self-assembled into micelles in water with the size of 42 ± 6 nm. MC-TPE shows thermoresponsivity and thermoreversibility in size, transmittance, and fluorescence, enabling it to work as a fluorescent thermosensor. Moreover, MC-TPE exhibits nontoxicity and biocompatibility, allowing its application in MCF-7 cell imaging. Therefore, this newly functional natural polymer shows promising potentials in the fields of sensing and bioimaging.

Improved Mechanical Properties and Sustained Release Behavior of Cationic Cellulose Nanocrystals Reinforeced Cationic Cellulose Injectable Hydrogels.

Polysaccharide-based injectable hydrogels have several advantages in the context of biomedical use. However, the main obstruction associated with the utilization of these hydrogels in clinical application is their poor mechanical properties. Herein, we describe in situ gelling of nanocomposite hydrogels based on quaternized cellulose (QC) and rigid rod-like cationic cellulose nanocrystals (CCNCs), which can overcome this challenge. In all cases, gelation immediately occurred with an increase of temperature, and the CCNCs were evenly distributed throughout the hydrogels. The nanocomposite hydrogels exhibited increasing orders-of-magnitude in the mechanical strength, high extension in degradation and the sustained release time, because of the strong interaction between CCNCs and QC chains mediated by the cross-linking agent (ß-glycerophosphate, ß-GP). The results of the in vitro toxicity and in vivo biocompatibility tests revealed that the hydrogels did not show obvious cytotoxicity and inflammatory reaction to cells and tissue. Moreover, DOX-encapsulated hydrogels were injected beside the tumors of mice bearing liver cancer xenografts to assess the potential utility as localized and sustained drug delivery depot systems for anticancer therapy. The results suggested that the QC/CCNC/ß-GP nanocomposite hydrogels had great potential for application in subcutaneous and sustained delivery of anticancer drug to increase therapeutic efficacy and improve patient compliance.

Hydrophobically modified quaternized celluloses as new dynamic coatings in CE for basic protein separation.

Hydrophobically modified quaternized celluloses (HMQCs), containing the quaternary ammonium groups and hexadecyl groups, were homogeneously synthesized as novel dynamic coatings for CE. Compared with quaternized cellulose coating, HMQC coating is able to generate stronger reversed EOF (ca. 10% increase) and has better efficiency in suppressing protein adsorption. The effects of the polymer concentration, the degree of hydrophobic substitution, and the buffer pH on the EOF mobility as well as on the separation of basic proteins were investigated in detail. It was shown that the use of HMQC coating could obviously improve the separation performance of basic proteins within a broad pH range. Five basic proteins (lysozyme, ribonuclease A, cytochrome c, bovine pancreatic trypsin inhibitor, and chymotrypsinogen) could be completely separated at pH 8.0. The successful performance of HMQC was further demonstrated by the analyses of lysozyme in tear and urine samples.

Effect of hemicellulose content on the solution properties of cellulose carbamates in NaOH/ZnO aqueous system.

Hemicellulose removal from bleached bamboo pulp is key to produce qualified dissolving pulps. In this work, alkali/urea aqueous solution was firstly applied to remove hemicellulose in bleached bamboo pulp (BP). The effect of urea usage, time and temperature on the hemicellulose content of BP was studied. The reduction of hemicellulose content from 15.9 to 5.7 % was achieved in 6 wt% NaOH/1 wt% urea aqueous solution at 40 °C for 30 min. Cellulose carbamates (CCs) were obtained from the esterification of BP with urea. The dissolution behavior of CCs in NaOH/ZnO aqueous solutions with different degree of polymerization (DP), hemicellulose and nitrogen contents were studied by using optical microscope and rheology. The highest solubility was up to 97.7 % when the hemicellulose was 5.7 % and Mη was 6.5 × 104 (g/mol). With the decrease of hemicellulose content from 15.9 % to 8.60 % and 5.70 %, the gel temperature increased from 59.0, 69.0 to 73.4 °C. The apparent gelation time increased from 5640 to 12,120 s with the hemicellulose content increased from 8.60 % to 15.9 %. CC solution with 5.70 % hemicellulose always keeps a liquid-state (G" > G') until the test time reached 17,000 s. The results showed that the removal of hemicellulose, the decrease of DP and the increase of esterification endowed CC with higher solubility and solution stability.

Fabrication of an exosome-loaded thermosensitive chitin-based hydrogel for dental pulp regeneration.

Injective thermosensitive hydrogels are considered promising scaffolds to trigger dental pulp regeneration in devitalized human teeth. In this study, we developed a hydroxypropyl chitin (HPCH)/chitin whisker (CW) thermosensitive hydrogel with enhanced mechanical properties and biological activities. Exosomes can serve as biomimetic tools for tissue engineering, but the rapid clearance of unconjugated exosomes in vivo limits their therapeutic effects. To address this challenge, exosomes were isolated from human pulp stem cells (hDPSCs) and directly embedded into the HPCH/CW pre-gel to form an exosome-loaded hydrogel (HPCH/CW/Exo). The exosome-loaded thermosensitive hydrogel can be easily injected into an irregular endodontic space and gelated in situ. In vitro cell experiments proved that the delivery of exosomes significantly improved the ability of hydrogels to promote odontogenesis and angiogenesis. Meanwhile, in vivo animal experiments revealed the formation of new dental pulp-like tissues in an implanted tooth root model. Therefore, the proposed hydrogel provides a great potential alternative to traditional root canal therapy in dental clinics.

Quaternized celluloses as new dynamic coatings in capillary electrophoresis for basic protein separation.

In this work, a series of quaternized celluloses (QCs), homogeneously synthesized in the NaOH/urea aqueous solutions, were studied as dynamic coatings for capillary electrophoresis. Capillaries coated with these cationic cellulose derivatives at the concentration as low as 3 µg/mL were able to generate a stable, reversed electroosmotic flow. The effects of QC molecular parameters, such as the degree of cationic substitution and molecular weight, and the effect of buffer pH on the EOF mobility as well as the separation of basic proteins were investigated in detail. It was shown that the use of QC coatings in CE could drastically reduce the analysis time and improve the separation performance within a broad pH range. Five basic proteins, that is, lysozyme, ribonuclease A, cytochrome C, bovine pancreatic trypsin inhibitor, and chymotrypsinogen were baselinely separated even at pH 8.0. The separation efficiency and analysis reproducibility demonstrated that the QC coatings were efficient in minimizing the adsorption of basic proteins on the fused silica capillary. The successful performance was further demonstrated for biosample analysis.

Rheological study of physical cross-linked quaternized cellulose hydrogels induced by ß-glycerophosphate.

As a weak base, ß-glycerophosphate (ß-GP) was used to spontaneously initiate gelation of quaternized cellulose (QC) solutions at body temperature. The QC/ß-GP solutions are flowable below or at room temperature but gel rapidly under physiological conditions. In order to clarify the sol-gel transition process of the QC/ß-GP systems, the complex was investigated by dynamic viscoelastic measurements. The shear storage modulus (G') and loss modulus (G″) as a function of (1) concentration of ß-GP (c(ß-GP)), (2) concentration of QC (c(QC)), (3) degree of substitution (DS; i.e., the average number of substituted hydroxyl groups in the anhydroglucose unit) of QC, (4) viscosity-average molecular weight (M(η)) of QC, and (5) solvent medium were studied by the oscillatory rheology. The sol-gel transition temperature of QC/ß-GP solutions decreased with an increase of c(QC) and c(ß-GP), the M(η) of QC, and a decrease of the DS of QC and pH of the solvent. The sol-gel transition temperature and time could be easily controlled by adjusting the concentrations of QC and ß-GP, M(η) and DS of QC, and the solvent medium. Gels formed after heating were irreversible; i.e., after cooling to lower temperature they could not be dissolved to become liquid again. The aggregation and entanglement of QC chains, electrostatic interaction, and hydrogen bonding between QC and ß-GP were the main factors responsible for the irreversible sol-gel transition behavior of QC/ß-GP systems.

Chitosan-based hydrogels with injectable, self-healing and antibacterial properties for wound healing.

Developing an efficient and available material for improved cutaneous tissue regeneration is a major challenge in healthcare. Inspired by the concept of moist wound healing, the injectable and self-healing adenine-modified chitosan (AC) hydrogels are designed to significantly accelerate wound healing without the addition of therapeutic drugs. A series of AC derivatives with degree of substitution (DS) ranging from 0.21 to 0.55 were synthesized in aqueous solutions, and the AC hydrogels were prepared by a simple heating/cooling process. AC hydrogels presented good self-healing, low swelling rate capacity, biocompatibility, promote cell proliferation and excellent hemostatic effect. The hydrogels displayed excellent antibacterial activities against gram-negative bacteria, gram-positive bacteria, fungi and drug-resistance bacteria. Moreover, the full-thickness skin defect model experiments showed that AC hydrogels could reduce inflammatory cell infiltration and accelerate wound healing significantly. The hydrogel can shed new light on designing of the multifunctional dressings for wound healing.

Electronic skin based on cellulose/KCl/sorbitol organohydrogel.

With the increasing interests in the fields of wearable devices, it is essential yet also challenging to develop electronic skin with customized functionalities, especially for harsh conditions. Herein, by using KCl as both anti-solvent for cellulose regeneration and ionic charge carrier in the cellulose gel network, cellulose/KCl/sorbitol organohydrogel (CKS) combining transparency (over 95% at 550 nm), stretchability (235%), high conductivity (3.88 S/m), and low temperature tolerance (-51.8 °C) was prepared. The CKS based electronic skin achieved simultaneous monitoring of object contact-separation/pressure, stretching/bending and thermal variation, with excellent reliability and stability even in harsh conditions, resembling the human skin with multiply functions. The CKS based electronic skin as efficient human-machine interface was also demonstrated. Furthermore, the CKS based triboelectric nanogenerator delivered a power density of 991 mW/m2, potential as mechanical energy harvesters for wearable devices. We believe the present work will inspire the development of cellulose based skin-like materials and contribute to the comprehensive utilization of naturel polymer in the field of smart devices.

Dual-network polyacrylamide/carboxymethyl chitosan-grafted-polyaniline conductive hydrogels for wearable strain sensors.

Conductive, wearable, and flexible hydrogel-based sensors are considered as promising applications in human motion detection and physiological signal monitoring. However, it is still a problem to integrate multiple functions into one material for the next-generation smart devices. Herein, we fabricated an ionic/electronic dual conductive hydrogel by combining the chemically crosslinked polyacrylamide (PAM) and the physically crosslinked carboxymethyl chitosan-grafted-polyaniline (CMCS-g-PANI)/Ag+ network. The double-network hydrogel displays a high stretchability, repeatable adhesiveness, antibacterial activities, and biocompatibility. It also has high sensitivity and stable electrical performance for wearable strain sensors. Furthermore, we assembled a self-powered strain sensor based on the conversion of chemical energy to electrical energy. It can be used for human motion detection even without external power supply. This work provides an avenue for the development of multifunctional hydrogels with outstanding mechanical and electronic performances for application in wearable electronic devices.

Dynamic viscoelastic properties of cellulose carbamate dissolved in NaOH aqueous solution.

Dynamic viscoelastic properties of cellulose carbamate (CC) dissolved in NaOH aqueous solution were systematically studied for the first time. CC was microwave-assisted synthesized from the mixture of cellulose and urea and then dissolved in 7 wt % NaOH aqueous solution precooled to -7 °C. The obtained CC solution is transparent and has good liquidity. To clarify the rheological behavior of the solution, the CC solutions were investigated by dynamic viscoelastic measurements. The shear storage modulus (G') and loss modulus (G'') as a function of the angular frequency (ω), concentration (c), nitrogen content (N %), viscosity-average molecular weight (M(η)), temperature (T), and time (t) were analyzed and discussed in detail. The sol-gel transition temperature of CC (M(η) = 7.78 × 10(4)) solution decreased from 36.5 to 31.3 °C with an increase of the concentration from 3.0 to 4.3 wt % and decreased from 35.7 to 27.5 °C with an increase of the nitrogen content from 1.718 to 5.878%. The gelation temperature of a 3.8 wt % CC solution dropped from 38.2 to 34.4 °C with the M(η) of CC increased from 6.35 × 10(4) to 9.56 × 10(4). The gelation time of the CC solution was relatively short at 30 °C, but the solution was stable for a long time at about 15 °C. Moreover, the gels already formed at elevated temperature were irreversible; that is, after cooling to a lower temperature including the dissolution temperature (-7 °C), they could not be dissolved to become liquid.

Novel multifunctional adenine-modified chitosan dressings for promoting wound healing.

Wound healing is a dynamic and intricate process, and newly dressings are urgently needed to promote wound healing over the multiple stages. Herein, two water-soluble adenine-modified chitosan (CS-A) derivatives were synthesized in aqueous solutions and freeze-dried to obtain porous sponge-like dressings. The novel derivatives displayed antibacterial activities against S. aureus and E. coli. Moreover, CS-A derivatives demonstrated excellent hemocompatibility and cytocompatibility, as well as promoted the proliferation of the wound cells by shortening the G1 phase and improving DNA duplication efficiency. The ability of CS-A sponges to promote wound healing was studied in a full-thickness skin defect model. The histological analysis and immunohistochemical staining showed that the wounds treated with CS-A sponges displayed fewer inflammatory cells, and faster regeneration of epithelial tissue, collagen deposition and neovascularization. Therefore, CS-A derivatives have potential application in wound dressings and provide new ideas for the design of multifunctional biomaterials.

Effect of the Degree of Acetylation of Chitin Nonwoven Fabrics for Promoting Wound Healing.

Chitin and chitosan have been extensively used as wound dressings because of their special functions to promote wound healing. However, there was little focus on the effects of the degree of acetylation (DA) on wound healing. In this work, the regenerated chitin nonwoven fabrics with DA values of 90, 71, 60, and 42% were prepared, and the morphology and physical performances of the fabrics were characterized. Moreover, the effects of DA of the chitin nonwoven fabrics on wound recovery were studied with a full-thickness skin defect model in rats. In vitro experiments indicated that the chitin nonwoven fabrics exhibited good biocompatibility and blood compatibility and a low blood-clotting index (BCI). In vivo experiments revealed that the chitin nonwoven fabrics could accelerate wound healing more effectively than gauze by promoting re-epithelialization and collagen deposition as well as by stimulating neovascularization. The results of the wound healing process showed that DA of the chitin nonwoven fabrics had a profound effect on promoting wound healing. Notably, the regenerated chitin nonwoven fabrics with 71% DA significantly improved the wound healing compared to the commercial wound dressing Algoplaque film. Therefore, the regenerated chitin nonwoven fabrics are promising candidates for wound healing.

Transparent, conductive cellulose hydrogel for flexible sensor and triboelectric nanogenerator at subzero temperature.

Herein, flexible, transparent and conductive cellulose hydrogels were directly fabricated by regenerating the chemically cross-linked cellulose in NaCl aqueous solution, without further treatment. NaCl played a dominant role on the mechanical, optical, conductive and anti-freezing properties of cellulose hydrogel, also endowed the hydrogel with safety. After optimization, the transparency, tensile strength, elongation at break and conductivity of the cellulose hydrogel reached 94 % at 550 nm, 5.2 MPa, 235 %, and 4.03 S/m, respectively, as well as low temperature tolerance down to -33.5 ℃. Furthermore, sensors based on cellulose hydrogel demonstrated fast response and stable sensitivity to tensile strain, compressive pressure, and temperature, at both room and subzero temperature, without obvious hysteresis. The cellulose hydrogel based triboelectric nanogenerator demonstrated stability and durability as energy harvester in harsh conditions. In addition, the established approach can be used to prepare flexible, transparent and conductive cellulose hydrogel with various salts, indicating universality, simplicity and sustainability for the fabrication of cellulose based flexible conductive devices.

Effect of molecular weight and degree of substitution of quaternized cellulose on the efficiency of gene transfection.

Quaternized celluloses (QCs) with different molecular weight (M(w)) and degree of cationic substitution (DS) were homogeneously synthesized in NaOH/urea aqueous solutions and were studied as gene carriers. QCs were evaluated for efficacy of nanoparticle formation, DNA binding efficiency, morphology, and in vitro gene transfection efficiency. The factors affecting the transfection efficiency, e.g., M(w), DS, and N/P ratios, have been evaluated. The cytotoxicity of QCs and QC/DNA complexes were evaluated in 293T cells and were found to be relatively low compared with 25 kDa PEI and PEI/DNA complex, which increased slightly with increasing of M(w) and DS. All QCs obtained could bind DNA efficiently, and QC/DNA complexes exhibited effective transfection in comparison to the naked DNA. More importantly, the QC/DNA complexes, were stable and the transfection efficiency was not inhibited in the presence of serum. The results revealed an important combined effect between M(w) and DS of QCs in determining transgene expression, and QCs with M(w) of about 8 x 10(4) g/mol and DS of about 0.6 displayed relatively higher transfection efficiencies attributed to the intermediate stability.

Ionically crosslinked chitosan/poly(acrylic acid) hydrogels with high strength, toughness and antifreezing capability.

A dual physically crosslinking (DPC) strategy is used to construct hydrogels with ultrahigh strength. First, polyelectrolyte complex (PEC) hydrogels were prepared through in situ polymerization of acrylic acid monomers in chitosan solutions. Subsequently, cations and anions were introduced into the PEC hydrogels to form strong electrostatic interactions with the polymer chains. The mechanical properties of the DPC hydrogels strongly depended on the ionic concentration and the valence state of the loading ions. The tensile strength of DPC-Na 8-20-2.0, DPC-Mg 8-20-2.0, DPCAl 8-20-2.0 and DPC-Sul 8-20-0.8 reached to 2.36, 12.59, 65.1 and 2.80 MPa, respectively, which were significantly higher than that of PEC 8-20 (0.29 MPa). Moreover, DPC-Na, DPC-Mg and DPC-Sul still maintained a good flexibility. Specifically, hydrogels of DPC-Ca exhibited ionic conductivity and freeze tolerance, which could be cooled to -20 °C without freezing. The DPC strategy opens an avenue to fabricate hydrogels with outstanding mechanical properties.

Self-healing and easy-to-shape mineralized hydrogels for iontronics.

Hydrogel-based multifunctional materials have attracted much attention. In this work, novel mineralized hydrogels were fabricated through physically cross-linked polyvinylpyrrolidone (PVP) and CaCO3. The mineralized hydrogels were prepared by simply mixing CaCl2, Na2CO3, and PVP in aqueous solutions. The CO32- induced the aggregation of the PVP chains and the CaCO3 particles in situ generated in the aqueous solution worked as fillers to strengthen the hydrogels. Based on this method, other kinds of mineralized hydrogels were prepared by replacing the Ca2+ with different metal ions. The mineralized hydrogels displayed shapeable, self-healing and thixotropic properties. Moreover, the mineralized hydrogel-based sensor showed good and stable sensitivity to compressive pressure, and could be used to monitor human actions. This work presents a facile method for preparing mineralized hydrogels, which are promising for various applications due to their outstanding properties.

Photo-reduction of Ag nanoparticles by using cellulose-based micelles as soft templates: Catalytic and antimicrobial activities.

Amphiphilic cellulose derivatives were synthesized from allyl cellulose (AC) and cystein (Cys)/n-dodecyl mercaptan (NDM) via the thiol-ene click reactions. The derivatives were self-assembled into micelles in distilled water, and the micelles sizes increased with an increase of the DSNDM. The amphiphilic cellulose micelles were served as the soft templates for the controllable synthesis of Ag nanoparticles (NPs) through the photo-reduction. Ag NPs were embedded and stabilized by the amphiphilic cellulose micelles, and their sizes increased from 3.1 to 14.4 nm with an increase of the original template sizes. The catalytic properties of the Ag-loaded micelles were evaluated by the reduction of p-nitropheonl to p-aminophenol. The results demonstrated that the Ag-loaded micelles exhibited excellent catalytic activity. The reduction followed the first-order rate law, and the reaction constant decreased with increasing size of Ag NPs. Moreover, the Ag-loaded micelles displayed good antimicrobial activities to both S. aureus and E. coli. Therefore, the Ag-loaded cellulose-based micelles have potential applications in various fields.

Homogeneous quaternization of cellulose in NaOH/urea aqueous solutions as gene carriers.

Quaternized celluloses (QCs) were homogeneously synthesized by reacting cellulose with 3-chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC) in NaOH/urea aqueous solutions. The structure and solution properties of the QCs were characterized by using elemental analysis, FTIR, (13)C NMR, SEC-LLS, viscometer, and zeta-potential measurement. The results revealed that water-soluble QCs, with a degree of substitution (DS) value of 0.20-0.63, could be obtained by adjusting the molar ratio of CHPTAC to anhydroglucose unit (AGU) of cellulose and the reaction time. The QC solutions in water displayed a typical polyelectrolyte behavior, and the intrinsic viscosity ([eta]) value determined from the Fuoss-Strauss method increased with increasing DS value. Moreover, two QC samples (DS = 0.46 and 0.63) were selected and studied as gene carriers. The results of gel retardation assay suggested that QCs could condense DNA efficiently. QCs displayed relatively lower cytotoxicity as compared with PEI, and QC/DNA complexes exhibited effective transfection compared to the naked DNA in 293T cells. The quaternized cellulose derivatives prepared in NaOH/urea aqueous solutions could be considered as promising nonviral gene carriers.