Crosslinking Density Of Hydrogels Research Articles

Photoactivatable poly(2-oxazoline)s enable antifouling hydrogel membrane coatings

In recent years, hydrophilic poly(2-oxazoline)s have been examined as an alternative polymer to poly(ethylene glycol) (PEG) with added stability and chemical versatility. They show excellent anti-fouling properties and, like PEG, are of interest in many fields where bio-inertness or anti-adhesiveness are important such as for medical devices, tissue engineering, biosensors, or drug delivery carriers. Surprisingly few studies have utilized this polymer class for the preparation of anti-fouling membranes. Here we describe a new termination reaction of the living cationic ring-opening polymerization of 2-oxazolines in which a benzophenone group is introduced as a photoactivatable terminal head group of poly(2-oxazoline)s. Using 4-vinylbenzyl chloride as initiator, heterotelechelic poly(2-methyl-2-oxazoline) (PMOXA) macromonomers were synthesized and copolymerized with hydroxyl-functional PMOXA macromonomers to yield photoactivatable PMOXA-based prepolymer bottle brushes. Likewise, star-PMOXAs were synthesized by using a trifunctional initiator. Photoactivatable PMOXA prepolymers allowed us to readily form anti-fouling hydrogels by a simple and versatile CH-insertion cross-linking (CHic) process. Hydrogels were applied to poly(ether sulfone) ultrafiltration membranes as pore coating and the pure water permeance (PWP) was investigated as a function of hydrogel architecture and cross-link density. Anti-fouling hydrogel pore-coated membranes having PWPs on the order of hundred kg·m−2·h−1·bar−1 were obtained.

Swift Covalent Gelation Coupled with Robust Wet Adhesive Powder: A Novel Approach for Acute Massive Hemorrhage Control in Dynamic and High-Pressure Wound Environments.

The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high-pressure wound environments. Traditional self-gelling powders, while beneficial due to their ease of application and rapid action, fall short in such challenging conditions. To bridge this gap, the research introduces a novel self-gelling powder that combines ultrafast covalent gelation and robust wet adhesion, presenting a significant advancement in acute hemorrhage control. This ternary system comprises ε-polylysine (ε-PLL) and 4-arm polyethylene glycol succinyl succinate (4-arm-PEG-NHS) forming the hydrogel framework. Na2HPO4 functions as the "H+ sucker" to expedite the amidation reaction, slashing gelation time to under 10 s, crucial for immediate blood loss restriction. Moreover, PEG chains' hydrophilicity facilitates efficient absorption of interfacial blood, increasing the generated hydrogel's cross-linking density and strengthens its tissue bonding, thereby resulting in excellent mechanical and wet adhesion properties. In vitro experiments reveal the optimized formulation's exceptional tissue compliance, procoagulant activity, biocompatibility and antibacterial efficacy. In porcine models of heart injuries and arterial punctures, it outperforms commercial hemostatic agent Celox, confirming its rapid and effective hemostasis. Conclusively, this study presents a transformative approach to hemostasis, offering a reliable and potent solution for the emergency management of massive hemorrhage.

PAM/CNTs-Au microcrack sensor with high sensitivity and wide detection range for multi-scale human motion detection

As the quintessential material for flexible sensors, conductive hydrogels face an inherent sensitivity-sensing range paradox and electrical-mechanical balance, which significantly curtail its applicability in multiscale motion detection. Inspired by the spider slit sensor, PAM/CNTs-Au hydrogel microcrack sensor is obtained by depositing conductive gold film on the surface of PAM/CNTs hydrogel using magnetron sputtering. By modulating the cross-linking density of conductive hydrogels and the content of carbon nanotubes (CNTs), it is possible to tailor the mechanical properties and adhesion of PAM/CNTs-Au hydrogel crack-based sensors. This self-adhering flexible sensor aids in minimizing detection errors arising from mechanical mismatch between flexible sensors and human tissues. Moreover, the exceptional electrical conductivity of CNTs, coupled with their unique one-dimensional structure, facilitates the formation of an interconnected conductive network "bridge" within the hydrogel. The harmonization of electrical and mechanical attributes in the PAM/CNTs flexible substrate is achieved by finely tuning the crosslinking density of the PAM hydrogel and the content of carbon CNTs. Simultaneously, the high-conductivity "islands" formed by the Au conductive layer during stretching ensures elevated sensitivity (gauge factor (GF) = 54.89) over an extensive detection range (>1200%). The distinctive "island-bridge" configuration of the PAM/CNTs-Au hydrogel microcrack sensor effectively suppresses crack propagation, thereby markedly augmenting the sensor's stability. Successful monitoring of physiological and motion signals across various scales attests to the potential of the PAM/CNTs-Au hydrogel microcrack sensor in wearable biosensor.

Moisture Absorbing and Water Self‐Releasing from Hybrid Hydrogel Desiccants

AbstractAtmospheric moisture is a valuable resource for fresh water and potentially sustainable energy. However, direct harvesting water from moisture (the vapor form) remains the most challenging. Hybrid desiccants made from hydrogels embedded with salt offer promise in absorbing moisture. However, the desorption process often requires additional energy to heat the samples. Here, poly(acrylic acid) (PAA) hydrogels embedded with lithium chloride are prepared, demonstratng simultaneous moisture absorption and self‐release of liquid water at room temperature with 50–90% relative humidity. The water self‐releasing process can be separated into two distinct stages: 1) surface release, where water droplets grow on the hydrogel surface due to differences in nucleation and diffusion rates, and 2) bulk release, triggered by the collapse of polymer chains, subsequently releasing water from the hydrogel network. Factors such as salt concentration, hydrogel crosslinking density, and film thickness are investigated to better understand the moisture absorption and water‐releasing processes. Moreover, hydrophobic domains are introduced onto the salt‐embedded PAA films, creating an edge effect that enhances the droplet growth rates. When the hydrophobic domains are patterned, the movement of released water can be guided, resulting in a threefold increase in water removal rate attributed to gravitational force.

Effect of Mechanical Stimuli on the Phenotypic Plasticity of Induced Pluripotent Stem-Cell-Derived Vascular Smooth Muscle Cells in a 3D Hydrogel.

Introduction: Vascular smooth muscle cells (VSMCs) play a pivotal role in vascular homeostasis, with dysregulation leading to vascular complications. Human-induced pluripotent stem-cell (hiPSC)-derived VSMCs offer prospects for personalized disease modeling and regenerative strategies. Current research lacks comparative studies on the impact of three-dimensional (3D) substrate properties under cyclic strain on phenotypic adaptation in hiPSC-derived VSMCs. Here, we aim to investigate the impact of intrinsic substrate properties, such as the hydrogel's elastic modulus and cross-linking density in a 3D static and dynamic environment, on the phenotypical adaptation of human mural cells derived from hiPSC-derived organoids (ODMCs), compared to aortic VSMCs. Methods and results: ODMCs were cultured in two-dimensional (2D) conditions with synthetic or contractile differentiation medium or in 3D Gelatin Methacryloyl (GelMa) substrates with varying degrees of functionalization and percentages to modulate Young's modulus and cross-linking density. Cells in 3D substrates were exposed to cyclic, unidirectional strain. Phenotype characterization was conducted using specific markers through immunofluorescence and gene expression analysis. Under static 2D culture, ODMCs derived from hiPSCs exhibited a VSMC phenotype, expressing key mural markers, and demonstrated a level of phenotypic plasticity similar to primary human VSMCs. In static 3D culture, a substrate with a higher Young's modulus and cross-linking density promoted a contractile phenotype in ODMCs and VSMCs. Dynamic stimulation in the 3D substrate promoted a switch toward a contractile phenotype in both cell types. Conclusion: Our study demonstrates phenotypic plasticity of human ODMCs in response to 2D biological and 3D mechanical stimuli that equals that of primary human VSMCs. These findings may contribute to the advancement of tailored approaches for vascular disease modeling and regenerative strategies.

3D bioprinting by reinforced bioink based on photocurable interpenetrating networks for cartilage tissue engineering

Cartilage has a limited ability to repair itself, highlighting the urgent need for suitable materials for cartilage regeneration. Achieving a balance between cell survival environment and hydrogel crosslinking density is crucial for photosensitive cell-laden cartilage repair materials to achieve both high strength and good cell viability. Here, an interpenetrating hydrogel consisted of methacrylate gelatin (GelMA) and glycidyl methacrylate silk fibroin (SG) was introduced. Compared to GelMA hydrogel, GelMA/SG had desired mechanical properties, with achieving up to 5 times of compression modulus and 6 times of compression failure energy. Meanwhile, the chondrocytes inside GelMA/SG exhibited great viability which was over 90 %. GelMA/SG as a bioink had favorable printability for digital light processing (DLP) bioprinting. The mesh DLP-printed scaffolds with high precision were created and GelMA/SG had a better shape retention ability than GelMA. Moreover, GelMA/SG cell-laden scaffolds had high strength while chondrocytes proliferated significantly in vitro culture. They were implanted under the skin of nude mice to evaluate ectopic chondrogenesis in vivo. The GelMA/SG cell-laden scaffolds indicated little deformation and high expression of collagen type II and glycosaminoglycans, which was advantageous for cartilage regeneration. The scaffold and its fabrication strategy provide potential solutions for clinical cartilage repair problems in the future.

Preparation, nano-mechanics and particle deposition behavior of thin, antifouling hydrogel coatings

Hydrogels based on hydrophilic, crosslinked polymer networks can reduce surface contamination in aqueous environments and continue attracting research interest due to their low adhesion, biocompatibility and tunable properties. In particular, sub-micron hydrogel films can potentially screen a surface from interaction with foulant colloids and microorganisms without compromising original functions, such as water permeation in membranes. This study focuses on the preparation of thin hydrogel films with the goal of understanding their adhesive and micromechanical properties, as well as factors affecting the dynamics of microparticle deposition on such films, mimicking the initial stages of surface fouling with colloids, microparticles and microorganisms. For this purpose, a simple procedure was developed to simultaneously crosslink and covalently anchor multi-arm-PEG precursors to a surface to form a submicron coating as a representative model. The effects of synthetic parameters and external conditions on adhesion and viscoelasticity were studied by force spectroscopy using polystyrene colloidal probes. The same particles were also employed in macroscopic deposition experiments in a parallel plate flow cell under identical solution conditions. Microscopic adhesion and elasticity were unaffected by the hydrogel crosslinking density and by salinity, but strongly affected by solution pH and dwell time, whereas macroscopic deposition was strongly affected both by salinity and by pH. These differences were ascribed to the effect of long-range double-layer forces, involved in deposition but absent in measurements of adhesion and elasticity. The results highlight the differences and similarities between the two types of measurements and underlying phenomena, as a step towards the understanding and rational design of soft antifouling coatings.

Characterization of Cross-Linking in Guar Gum Hydrogels via the Analysis of Thermal Decomposition Behavior and Water Uptake Kinetics

This study aimed to explore a test method for evaluating the effective cross-linking density of hydrogels. A guar gum–epichlorohydrin hydrogel (GEH) was prepared using guar gum (GG) as the raw material and epichlorohydrin (ECH) as the cross-linking agent. The thermal and mechanical properties, equilibrium swelling rate (ESR), water uptake (WU), and mass cross-linking degree of the hydrogels were assessed. Furthermore, the diffusion behavior of water molecules in the freeze-dried GEH was investigated. The experimental results showed the significance of the initial decomposition temperature (Ti) and final decomposition temperature (Tf) of the freeze-dried GEHs in determining the effective cross-linking density. The water uptake kinetics of the freeze-dried GEH was consistent with the linear fitting of the pseudo-second-order kinetic model and nonlinear fitting of the Fickian diffusion model, suggesting that chemisorption dominated the water absorption process in the GEH. Therefore, the effective cross-linking density of the hydrogels could be determined from the thermodynamic analysis and the diffusive behavior of water molecules in the gels. The thermal stability and water diffusion kinetics of the hydrogels were closely linked to the effective cross-linking density and pendant modification.

Modulation of composite hydrogel consisting of TEMPO-oxidized cellulose nanofibers and cationic guar gum

The applications of hydrogels are prominently affected by the modulation of their structure and performance. We herein systematically implemented the modulation of an all-polysaccharide hydrogel consisting of TEMPO-oxidized cellulose nanofibers (TOCN) and cationic guar gum (CGG). Four different factors including the carboxylate content and size of TOCN, the freezing-thawing treatment and solid content of hydrogel were studied to disclose their influence on the structure and property of TOCN/CGG hydrogel. The results indicated that the increase of carboxylate content of TOCN, the number of freezing-thawing cycles and solid content all increased the crosslinking density of hydrogel as a result of the improved interactions. Accordingly, the hydrogels exhibited more compact structures and enhanced rheological properties. The influence of TOCN size on the hydrogel structure and property was demonstrated to be dependent on the compromise between the exposed functional groups of TOCN and their ability in generating entanglements inside the hydrogel. This work helps shed light on the modulation of hydrogel structure and performance, which might facilitate the exploration of hydrogel applications.

The Effect of Crosslinking Density on Nasal Chondrocytes' Redifferentiation.

Hydrogels appear to be an attractive class of biomaterial for cartilage tissue engineering due to their high water content, excellent biocompatibility, tunable stiffness, etc. The crosslinking density of the hydrogel can affect their viscoelastic property, and therefore potentially impact the chondrogenic phenotype of re-differentiated chondrocytes in a 3D microenvironment through physical cues. To understand the effect of crosslinking densities on chondrocytes phenotype and cellular interaction with the hydrogel, this study utilized a clinical grade thiolate hyaluronic acid and thiolate gelatin (HA-Gel) hydrogel, crosslinked with poly(ethylene glycol) diacrylate to create various crosslinking densities. The HA-Gel hydrogels were then mixed with human nasal chondrocytes to generate neocartilage in vitro. The influence of the hydrogel crosslinking density and the viscoelastic property on the cell behaviours on the gene and matrix levels were evaluated using biochemistry assays, histology, quantitative polymerase chain reaction (qPCR) and next-generation sequencing (RNA seq). In general, the differences in the storage modulus of the HA-Gel hydrogel are not enough to alter the cartilaginous gene expression of chondrocytes. However, a positively correlated trend of PPAR-γ gene expression to the crosslinking density was measured by qPCR. The RNA-seq results have shown that 178 genes are significantly negatively correlated and 225 genes are positively correlated to the crosslinking density, which is worth investigating in the future studies.

An experimental and theoretical approach to understand the interaction between particles and mucosal tissues.

Nanonization of poorly water-soluble drugs has shown great potential in improving their oral bioavailability by increasing drug dissolution rate and adhesion to the gastrointestinal mucus. However, the fundamental features that govern the particle-mucus interactions have not been investigated in a systematic way before. In this work, we synthesize mucin hydrogels that mimic those of freshly excised porcine mucin. By using fluorescent pure curcumin particles, we characterize the effect of particle size (200 nm, and 1.2 and 1.3 μm), concentration (18, 35, and 71 μg mL-1), and hydrogel crosslinking density on the diffusion-driven particle penetration in vitro. Next, we derive a phenomenological model that describes the physics behind the diffusion-derived penetration and considers the contributions of the key parameters assessed in vitro. Finally, we challenge our model by assessing the oral pharmacokinetics of an anti-cancer model drug, namely dasatinib, in pristine and nanonized forms and two clinically relevant doses in rats. For a dose of 10 mg kg-1, drug nanonization leads to a significant ∼8- and ∼21-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the unprocessed drug. When the dose of the nanoparticles was increased to 15 mg kg-1, the oral bioavailability increased though not significantly, suggesting the saturation of the mucus penetration sites, as demonstrated by the in vitro model. Our overall results reveal the potential of this approach to pave the way for the development of tools that enable a more rational design of nano-drug delivery systems for mucosal administration. STATEMENT OF SIGNIFICANCE: The development of experimental-theoretical tools to understand and predict the diffusion-driven penetration of particles into mucus is crucial not only to rationalize the design of nanomedicines for mucosal administration but also to anticipate the risks of the exposure of the body to nano-pollutants. However, a systematic study of such tools is still lacking. Here we introduce an experimental-theoretical approach to predict the diffusion-driven penetration of particles into mucus and investigate the effect of three key parameters on this interaction. Then, we challenge the model in a preliminary oral pharmacokinetics study in rats which shows a very good correlation with in vitro results. Overall, this work represents a robust platform for the modelling of the interaction of particles with mucosae under dynamic conditions.

Crack propagation and arrests in gelatin hydrogels are linked to tip curvatures.

Gelatin hydrogels are attractive scaffold materials for tissue engineering applications as they provide motifs for cell attachment, undergo large deformations, and are tunable. Low toughness and brittle fractures however limit their use in load bearing applications. An investigation of crack tip processes and mechanisms of crack propagation is warranted to link fracture properties with material microstructure. We cross-linked gelatin using glutaraldehyde to obtain low cross-linked control hydrogels and used an additional cross-linker, methylglyoxal, to fabricate MGO hydrogels with higher cross-links. We quantified fractures in the gelatin hydrogels from both groups using pure shear notch tests and characterized strain fields near the crack tip using 2-D digital image correlation. We used a numerical method based on Taylor's series expansion to measure the crack tip curvatures in the hydrogels. This method captures tip curvatures better than the parabolic method routinely used in studies. Results from our study show that cracks in gelatin hydrogels underwent frequent arrests during propagation through the specimen width in both groups. MGO hydrogels had 85% enhanced fracture toughness and a significantly higher number of stalls compared to the control group. Crack initiations following stalls in the sample correlated with low tip curvatures in both hydrogel groups. We also show that mechanical stretching blunts the crack tip before crack propagation; the degree of blunting was independent of the cross-link density and elastic modulus of the gelatin hydrogels. These results show a link between crack growth and the tip curvature in cross-linked gelatin hydrogels, and offer potential insights for the development of tougher hydrogels.

Aptamer-functionalized smart photonic hydrogels: application for the detection of thrombin in human serum

Smart photonic hydrogels based on two-dimensional photonic crystals (2DPC) provide a promising sensing platform for constructing novel chemical and biological sensors due to their facile optical signal readout and highly sensitive responsivity toward target analytes. Aptamers, as recognition elements with high selectivity and affinity, are extensively used to construct a variety of sensors. Herein, we developed two partially base complementary aptamer-functionalized 2DPC hydrogels as aptasensors for the detection of thrombin (TB) in human serum. The photonic hydrogel aptasensors swelled upon exposure to TB solution, leading to an increase in the particle spacing of the 2DPCs. The particle spacing changes were acquired by simply measuring the diameters of the Debye ring diffracted by the 2DPCs without the requirement of sophisticated instruments. The aptasensor swelling resulted from the decrease in the hydrogel cross-linking density induced by the specific binding between one of the aptamers and TB and the increase in hydrogel mixing free energy induced by the introduction of TB. The particle spacing increase of the optimized aptasensor was linear over the TB concentration range of 1–500 nM, and the limit of detection was 0.64 nM. The constructed 2DPC hydrogel aptasensor was used to detect TB in human serum and achieved recoveries of 95.74–104.21% and a relative standard deviation of 2.52–6.58%, showing the practicability and accuracy of the sensor. The aptamer-actuated 2DPC hydrogel biosensor provides a new strategy for designing other target molecule-sensitive aptasensors, showing great potential for development into home kits.

Tyramine-Functionalized Alginate-Collagen Hybrid Hydrogel Inks for 3D-Bioprinting.

Extrusion-based 3D-bioprinting using hydrogels has exhibited potential in precision medicine; however, researchers are beset with several challenges. A major challenge of this technique is the production of constructs with sufficient height and fidelity to support cellular behavior in vivo. In this study, we present the 3D-bioprinting of cylindrical constructs with tunable gelation kinetics by controlling the covalent crosslinking density and gelation time of a tyramine-functionalized alginate hydrogel (ALG-TYR) via enzymatic reaction by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The extruded filament was crosslinked for a second time on a support bath containing H2O2 to increase fidelity after printing. The resulting tubular construct, with a height of 6 mm and a wall thickness of 2 mm, retained its mechanical properties and had a maximum 2-fold swelling after 2 d. Furthermore, collagen (COL) was introduced into the ALG-TYR hydrogel network to increase the mechanical modulus and cell cytocompatibility, as the encapsulated fibroblast cells exhibited a higher cell viability in the ALG-TYR/COL construct (92.13 ± 0.70%) than in ALG-TYR alone (68.18 ± 3.73%). In summary, a vascular ECM-mimicking scaffold was 3D-bioprinted with the ALG-TYR/COL hybrid hydrogel, and this scaffold can support tissue growth for clinical translation in regenerative and personalized medicine.

Super-strong and anti-tearing poly(vinyl alcohol)/graphene oxide nano-composite hydrogels fabricated by formation of multiple crosslinking bonding network structure

As load-bearing material in biomedical-applications as cartilage replacement, artificial meniscus and tendons, etc., poly(vinyl alcohol) (PVA)/graphene oxide (GO)-tannic acid (TA) nano-composite hydrogels with multiple-crosslinking network were fabricated by establishing freezing/thawing-annealing-swelling method. By TA anchoring, PVA molecules were grafted onto GO surface efficiently, and strong interfacial interaction led to exfoliation and uniform distribution of GO in matrix. By introducing annealing process, the crystallinity and crystallite size of PVA increased and introducing GO-TA led to more perfect and denser crystalline structure, while physical crosslinking network centered on GO-TA and hydrogen bond-abundant crystalline phase formed, resulting in increasing crosslinking density of hydrogel. By further swelling in CaCl2 aqueous solution, hydroxyl-Ca2+ coordination formed, and multiple-crosslinking network was constructed with high crosslinking density. The tensile strength and fracture toughness of composite hydrogel were remarkably improved, reaching 14.38 MPa/27.93 MJ/m3, approximately 11-/26-fold higher than those of neat PVA hydrogel, while tearing strength was significantly enhanced, attributed to high energy dissipation through unzipping multiple interactions.

The influence of poly(allylamine hydrochloride) hydrogel crosslinking density on its thermal and phosphate binding properties

Sevelamer hydrochloride (SH) or Renagel® is an effective phosphate binder prescribed to prevent the absorption of phosphate in end stage renal disease (ESRD) patients. The relationship between SH structure and binding capacity and affinity is very important and can be used in characterising the sensitivity of the hydrogel to binding conditions. Thus, a series of hydrogels were prepared by varying the amount of crosslinker, whilst the other hydrogel components were kept constant. Variation of this parameter influenced the hydrogel structure as shown by swelling data, differential scanning calorimetry and solid state nuclear magnetic resonance spectroscopy. The hydrogels’ physical characteristics were found to correlate with the number of phosphate binding sites and affinity obtained from the Langmuir–Freundlich Isotherm (L–FI) and affinity distribution spectra (AD). The hydrogels formed using lower amounts of crosslinker showed a slight increase in binding capacity but with lower affinity. However, the influence of the pH of the binding media on the binding parameters of sevelamer hydrochloride was significant. This is the first report on the use of AD spectra generated from L-FI binding parameters in hydrogels, which demonstrates the sensitivity of the affinity and binding site numbers to changes in hydrogel physical properties and the pH of the binding media.

A solid hydrogel electrolyte-based micro fuel cell integrated with fuel/electrolyte storage and supply function

<p indent="0mm">The development of modern electronic equipment has promoted the requirement of portable energy conversion devices. Fuel cell technology provides clean energy, which is pollution-free and environmentally friendly. It has several advantages, including instant charge and discharge, high energy conversion efficiency, and easy integration. However, some disadvantages, such as high membrane cost, membrane aging degradation, water management, and extra ohmic resistance, always accompany the conventional proton exchange membrane fuel cells. In addition, the need for fuel tanks increases the system cost and complexity and is unfavorable for miniaturization. Meanwhile, the consumption of additional pump power to supply fuel can reduce the net output power. Hydrogel is a solid-state electrolyte crosslinked via a three-dimensional (3D) polymer network. The porous structure possesses the abilities of water absorption and retention and enables fast mass transport on a large surface. To simplify the fuel cell system and improve its portability, a miniature fuel cell integrated with the fuel/electrolyte is proposed, complemented by the water retention and ionic conductivity of the hydrogel. Polyvinyl alcohol (PVA) hydrogel is prepared via cyclic freezing and thawing processes. The effects of the fabrication parameters, such as swelling and conductivity of the hydrogel electrolyte, are discussed, and the fuel cell equipped with hydrogel is set up. The micromorphology and element distribution of PVA hydrogel are evaluated via physical characterization. PVA hydrogel has an abundant 3D-network porous structure. PVA polymer chain is uniformly crosslinked, and C and O elements are evenly distributed on the hydrogel skeleton. Fourier transform infrared results reveal numerous hydrophilic groups in PVA hydrogel, including –OH and C–O, contributing to the high aqueous electrolyte absorption ability. The effect of fabrication parameters on the swelling properties of PVA hydrogel is studied. The high concentration and efficient repetitive freezing-thawing can improve the crosslinking density of the PVA hydrogel, firmness of the hydrogel skeleton, and swelling equilibrium. The PVA hydrogel in 5% can reach the maximum swelling ratio of 45%. The ionic conductivity of the PVA hydrogel after swelling the electrolyte is studied via the two-probe AC impedance method. The various freezing-thawing cycles have an evident influence on the crosslinking density and pore size of the hydrogel, contributing to the absorption ability of the sulfuric acid solution and hydrogel conductivity. The ionic conductivity of the PVA hydrogel in 5% by three freeze-haw cycles is up to 173.61 mS/cm, facilitating the hydrogen ion conduction in the fuel cell. Moreover, the effects of hydrogel thickness, fuel concentration, and electrolyte concentration on the fuel cell performance are studied. Consequently, when the hydrogel electrolyte thickness is <sc>6 mm</sc> using <sc>6 mol/L</sc> HCOOH and <sc>1 mol/L</sc> H₂SO₄, the maximum power density is <sc>2.5 mW/cm²</sc>, and the limiting current density is <sc>15.2 mA/cm².</sc> The results suggest that the fuel cell can be used to power miniature portable electronic devices.

A pH-Responsive Liquid Crystal Hydrogel Actuator with Calcium-Induced Reprogrammable Shape Fixing

Soft polymer actuators have myriad applications and have therefore gained considerable attention in recent years. However, it remains challenging to prepare soft actuators with predefined shapes. Here, a bilayer polymer actuator with a (re)programmable shape is prepared from a microporous anisotropic polypropylene scaffold and a thin, pH-responsive liquid crystalline network (LCN) layer. The hydrogen bonds between dimerized benzoic acid derivatives in the LCN can be disrupted by an alkaline treatment, resulting in a pH-responsive LCN hydrogel layer. The pH-responsive actuation is governed by both the anisotropic mechanical properties of the scaffold and the cross-link density of the LCN hydrogel. Ca2+ ions can be used to chemically cross-link the actuator resulting in an initial programmed shape. The shape fixing can be reversed by removing the Ca2+ ions with an ethylenediaminetetraacetic acid (EDTA) solution. The shape fixing can be performed locally, resulting in pH-responsive actuators with three-dimensional initial configurations of choice.

Grayscale Stereolithography of Gradient Hydrogel with Site‐Selective Shape Deformation

AbstractHydrogels can convert external stimuli into shape deformation and mechanical motion, leading to the potential applications in intelligent devices and soft robotics. However, it is difficult to control the site‐selective shape deformation in a single hydrogel system in comparison with the traditional bilayer actuators with difference in structure or composition across the thickness. Here, a strategy to achieve the programmable shape deformation of hydrogel from a single precursor by grayscale stereolithography is proposed. The designed grayscale patterns can govern the spatially gradient crosslinking density of hydrogels, which leads to the heterogeneity in physicochemical performance, especially swelling ability. As a result, the swelling mismatch inducing the nonuniform internal stresses can drive the printed hydrogels to deform as the expected shape in three dimensions although there is no apparent asymmetric features and bilayer configuration. Grayscale light intensity and exposure time, as the digital printing codes can parametrically regulate the predictable shape deformation. More importantly, hydration and dehydration characterizations can endow the reversible feature of shape deformation hydrogel, benefiting to design the hydrogel actuators and sensitive devices. It is believed that integration of the advanced grayscale stereolithography together with the functional hydrogels uncovers a facile strategy to broad opportunities for sensors, soft robots, actuators, and so on.

Biomimetic stiffening of cell-laden hydrogels via sequential thiol-ene and hydrazone click reactions

Hydrogels with dynamically tunable crosslinking are invaluable for directing stem cell fate and mimicking a stiffening matrix during fibrosis or tumor development. The increases in matrix stiffness during tissue development are often accompanied by the accumulation of extracellular matrices (e.g., collagen, hyaluronic acid (HA)), a phenomenon that has received little attention in the development of dynamic hydrogels. In this contribution, we present a gelatin-based cell-laden hydrogel system capable of being dynamically stiffened while accumulating HA, a key glycosaminoglycans (GAG) increasingly deposited by stromal cells during tumor progression. Central to this strategy is the synthesis of a dually-modified gelatin macromer – gelatin-norbornene-carbohydrazide (GelNB-CH), which is susceptible to both thiol-norbornene photopolymerization and hydrazone click chemistry. We demonstrate that the crosslinking density of cell-laden thiol-norbornene hydrogels can be dynamically tuned via simple incubation with aldehyde-bearing macromers (e.g., oxidized dextran (oDex) or oHA). The GelNB-CH hydrogel system is highly cytocompatible, as demonstrated by in situ encapsulation of pancreatic cancer cells (PCC) and cancer-associated fibroblasts (CAF). This unique dynamic stiffening scheme provides a platform to study tandem accumulation of HA and elevation in matrix stiffness in the pancreatic tumor microenvironment. Statement of significanceHydrogels permitting on-demand and secondary crosslinking are ideal for mimicking a stiffening tumor microenvironment (TME). However, none of the current dynamic hydrogels account for both stiffening and accumulation of hyaluronic acid (HA), a major extracellular matrix component increasingly deposited in tumor stromal tissues, including pancreatic ductal adenocarcinoma (PDAC). The current work addresses this gap by developing a dynamic hydrogel system capable of simultaneously increasing stiffness and HA accumulation. This is achieved by a new gelatin macromer permitting sequential thiol-norbornene (for primary network crosslinking) and hydrazone click chemistry (for bioinert or biomimetic stiffening with oxidized dextran (oDex) or oHA, respectively). The results of this study provide new insights into how dynamically changing physicochemical matrix properties guide cancer cell fate processes.