Giant Iontronic Flexoelectricity in Soft Hydrogels Induced by Tunable Biomimetic Ion Polarization.

Flexoelectricity features the strain gradient-induced mechanoelectric conversion using materials not limited by their crystalline symmetry, but state-of-the-art flexoelectric materials exhibit very small flexoelectric coefficients and are too brittle to withstand large deformations. Here, inspired by the ion polarization in living organisms, this paper reports the giant iontronic flexoelectricity of soft hydrogels where the ion polarization is attributed to the different transfer rates of cations and anions under bending deformations. The flexoelectricity is found to be easily regulated by the types of anion-cation pairs and polymer networks in the hydrogel. A polyacrylamide hydrogel with 1 m NaCl achieves a record-high flexoelectric coefficient of ≈1160 µC m-1, which can even be improved to ≈2340 µC m-1 by synergizing with the effects of ion pairs and extra polycation chains. Furthermore, the hydrogel as flexoelectric materials can withstand larger bending deformations to obtain higher polarization charges owing to its intrinsic low modulus and high elasticity. A soft flexoelectric sensor is then demonstrated for object recognition by robotic hands. The findings greatly broaden the flexoelectricity to soft, biomimetic, and biocompatible materials and applications.

Regulated Self-Folding in Multi-Layered Hydrogels Considered with an Interfacial Layer.

Multi-layered hydrogels consisting of bi- or tri-layers with different swelling ratios are designed to soft hydrogel actuators by self-folding. The successful use of multi-layered hydrogels in this application greatly relies on the precise design and fabrication of the curvature of self-folding. In general, however, the self-folding often results in an undesired mismatch with the expecting value. To address this issue, this study introduces an interfacial layer formed between each layered hydrogel, and this layer is evaluated to enhance the design and fabrication precision. By considering the interfacial layer, which forms through diffusion, as an additional layer in the multi-layered hydrogel, the degree of mismatch in the self-folding is significantly reduced. Experimental results show that as the thickness of the interfacial layer increases, the multi-layered hydrogel exhibits a 3.5-fold increase in its radius of curvature during the self-folding. In addition, the diffusion layer is crucial for creating robust systems by preventing the separation of layers in the muti-layered hydrogel during actuation, thereby ensuring the integrity of the system in operation. This new strategy for designing multi-layered hydrogels including an interfacial layer would greatly serve to fabricate precise and robust soft hydrogel actuators.

Influence of Elasticity of Hydrogel Nanoparticles on Their Tumor Delivery.

Polymeric nanocarriers have a broad range of clinical applications in recent years, but an inefficient delivery of polymeric nanocarriers to target tissues has always been a challenge. These results show that tuning the elasticity of hydrogel nanoparticles (HNPs) improves their delivery efficiency to tumors. Herein, a microfluidic system is constructed to evaluate cellular uptake of HNPs of different elasticity under flow conditions. It is found that soft HNPs are more efficiently taken up by cells than hard HNPs under flow conditions, owing to the greater adhesion between soft HNPs and cells. Furthermore, in vivo imaging reveals that soft HNPs have a more efficient tumor delivery than hard HNPs, and the greater targeting potential of soft HNPs is associated with both prolonged blood circulation and a high extent of cellular adhesion.

Stretchable, compressible, and conductive hydrogel for sensitive wearable soft sensors.

Conductive hydrogels hold great promises in wearable soft electronics. However, the weak mechanical properties, low sensitivity and the absence of multifunctionalities (e.g., self-healing, self-adhesive, etc.) of the conventional conductive hydrogels limit their applications. Thus, developing multifunctional hydrogels may address some of these technical issues. In this work, a multifunctional conductive hydrogel strain sensor is fabricated by incorporating a conductive polymer Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) into a mechanically robust poly (vinyl alcohol) (PVA)/ poly (acrylic acid) (PAA) double network (DN) hydrogel. The as-prepared hydrogel sensor could span a wide spectrum of mechanical properties by simply tuning the polymer composition and the number of freezing-thawing cycles. In addition, the dynamic hydrogen bonding interactions endow the hydrogel sensor with self-healing property and reversible adhesiveness on diverse substrates. Moreover, the hydrogel sensor shows high sensitivity (Gauge Factor from 2.21 to 3.82) and can precisely detect some subtle human motions (e.g., pulse and vocal cord vibration). This work provides useful insights into the development of conductive hydrogel-based wearable soft electronics.

Soft Stretchable Conductive Carboxymethylcellulose Hydrogels for Wearable Sensors.

Hydrogels that have a capability to provide mechanical modulus matching between time-dynamic curvilinear tissues and bioelectronic devices have been considered tissue-interfacing ionic materials for stably sensing physiological signals and delivering feedback actuation in skin-inspired healthcare systems. These functionalities are totally different from those of elastomers with low ionic conductivity and higher stiffness. Despite such remarkable progress, their low conductivity remains limited in transporting electrical charges to internal or external terminals without undesired information loss, potentially leading to an unstable biotic-abiotic interfaces in the wearable electronics. Here, we report a soft stretchable conductive hydrogel composite consisting of alginate, carboxymethyl cellulose, polyacrylamide, and silver flakes. This composite was fabricated via sol-gel transition. In particular, the phase stability and low dynamic modulus rates of the conductive hydrogel were confirmed through an oscillatory rheological characterization. In addition, our conductive hydrogel showed maximal tensile strain (≈400%), a low deformations of cyclic loading (over 100 times), low resistance (≈8.4 Ω), and a high gauge factor (≈241). These stable electrical and mechanical properties allowed our composite hydrogel to fully support the operation of a light-emitting diode demonstration under mechanical deformation. Based on such durable performance, we successfully measured the electromyogram signals without electrical malfunction even in various motions.

Supramolecular Assembly of Shape Memory and Actuating Hydrogels for Programmable Shape Transformation.

The deformable diversity of organisms in nature has inspired the development of bionic hydrogel actuators. However, the anisotropic structures of hydrogel actuators cannot be altered after the fabrication process, which restricts hydrogel actuators to provide complex and diverse shape deformations. Herein, we propose a dual programming method to generate numerous anisotropic structures from initial isotropic gelatin-containing hydrogels; the isotropic hydrogel blocks could be first assembled into anisotropic structures based on the coil-triple helix transition of gelatin, and then, the assembled hydrogels could further be fixed into various temporary anisotropies, so that they can produce complex and diverse deformations under the stimulation of pH. In addition, the shape programming and deformation behaviors are reversible. This dual programming method provides more potential for the application of hydrogel actuators in soft robots and bionics.

The Soft and High Actuation Response of Graphene Oxide/Gelatin Soft Gel.

The high actuation response of soft gel from a graphene oxide/gelatin composite was prepared as an alternative material in soft robotics applications. Graphene oxide (GO) was selected as the electroresponsive (ER) particle. GO was synthesized by modifying Hummer's method at various ratios of graphite (GP) to potassium permanganate (KMnO4). To study the effect of ER particles on electromechanical properties, GO was blended with gelatin hydrogel (GEL) at various concentrations. The electrical properties of the ER particles (GO and GP) and matrix (GEL) were measured. The capacitance (C), resistance (R), and dielectric constant of the GO/GEL composite were lower than those of the GO particles but higher than those of the GEL and GP/GEL composite at the given number of particles. The effects of external electric field strength and the distance between electrodes on the degree of bending and the dielectrophoresis force (Fd) were investigated. When the external electric field was applied, the composite bent toward electrode, because the electric field polarized the functional group of polymer molecules. Under applied 400 V/mm, the GO/GEL composite (5% w/w) showed the highest deflection angle (θ = 82.88°) and dielectrophoresis force (7.36 N). From the results, we conclude that the GO/GEL composite can be an alternative candidate material for electromechanical actuator applications.

A bioinspired synthetic soft hydrogel for the treatment of dry eye.

Natural soft hydrogels are unique elastic soft materials utilized by living organisms for protecting delicate tissues. Under a theoretical framework derived from the Blob model, we chemically crosslinked high molecular weight hyaluronic acid at a concentration close to its overlap concentration (c*), and created synthetic soft hydrogels that exhibited unique rheological properties similar to a natural soft hydrogel: being dominantly elastic under low shear stress while being viscous when the stress is above a small threshold. We explored a potential application of the hyaluronic acid-based soft hydrogel as a long-acting ocular surface lubricant and evaluated its therapeutic effects for dry eye. The soft hydrogel was found to be biocompatible after topical instillation on experimental animals' and companion dogs' eyes. In a canine clinical study, twice-a-day ocular instillation of the soft hydrogel in combination with cyclosporine for 1 month improved the clinical signs in more than 65% of dog patients previously unresponsive to cyclosporine treatment.

Production of wheat germ oil containing multilayer hydrogel dressing.

A composite wound dressing has been developed by combining different layers consisting of polymers and textiles. Wheat germ oil (WGO) loaded hydrogels have successfully formed on textile nonwovens by cross-linking sodium alginate (SA) with poly(ethylene glycol) diglycidyl ether (PEGDGE). Following freeze-drying, textile-hydrogel composites have been examined according to their physical properties, pH, fluid handling capacity, water vapour permeability, morphology, chemical structure, and cytotoxicity. Hydrogels containing WGO swelled less than pristine hydrogels. Samples with 1% WGO and no WGO showed swelling of 5.9 and 10.5 g/g after 8 h. WGO inclusion resulted in reduced, but more stable fluid handling properties, with more uniform pore distribution (100-200 µm). Moreover, the proliferation of NIH/3T3 cells significantly improved with 1% WGO contained hydrogels. Also, commercial self-adhesive dressings that secure the hydrogels to the wound area were investigated regarding transfer properties. The proposed product demonstrated 8.05 cm3/cm2/s and 541.37 g/m2/day air and water vapour permeability.

Hierarchically Curved Gelatin for 3D Biomimetic Cell Culture.

The stiffness, microcurvature, and meso-curvature of cellular microenvironments can significantly alter cell and tissue function. However, it is challenging to produce in vitro tissue models that feature tunability in shape, stiffness, and curvature simultaneously in a high-throughput and cost-effective manner. One of the significant challenges is the fragility of micropatterns in soft and biocompatible hydrogels. Here, we describe an approach that combines reflow photolithography, soft lithography, and strain engineering to create soft anatomically mimetic gelatin cell culture models. The models can be mechanically tuned to have stiffnesses as low as 400 Pa to as high as 50 kPa featuring hierarchical curvature at two length scales: the cellular length scale of 12 to 120 µm, and the mesoscale of 1-4 mm. We characterize the microstructured gels using optical microscopy and rheometry, highlighting tunability in the hierarchical curvature, modulus, and shape. Also, collagen-based gelatin offers high-level biocompatibility and bypasses the need for additional surface modification to enhance cell adhesion. We anticipate that this approach could advance anatomically accurate in vitro 3D cell culture models of relevance to biofabrication, cell biology, and drug screening.

Synthesis and Characterization of Dual Stimuli-Sensitive Biodegradable Polyurethane Soft Hydrogels for 3D Cell-Laden Bioprinting.

Three-dimensional bioprinting serves as an attractive platform to fabricate customized tissue-engineered substitutes from biomaterials and cells for the repair or replacement of injured tissues and organs. A common challenge for 3D bioprinting materials is that the structures printed from the biodegradable polymer hydrogels tend to collapse because of the poor mechanical stability. In this study, dual stimuli-responsive biodegradable polyurethane (PU) dispersions (PUA2 and PUA3) were synthesized from an eco-friendly waterborne process. Acrylate group was introduced in the PU chain end to serve as a photosensitive moiety for UV-induced cross-linking and improvement of the printability, while mixed oligodiols in the soft segment remained to be the thermosensitive moiety. The photo/thermal-induced morphological changes of PU nanoparticles were verified by dynamic light scattering, small-angle X-ray scattering, and rheological measurement of the dispersions. It was observed that these PU nanoparticles became more rod-like in shape after UV treatment and formed compact packing structures upon further heating. With the thermosensitive properties, these UV-cured PU dispersions underwent rapid thermal gelation with gel moduli in the range 0.5-2 kPa near body temperature. The rheological properties of the PU hydrogels including dynamic viscoelasticity, creep recovery, and shear thinning behavior at 37 °C were favorable for processing by microextrusion-based 3D printing and could be easily mixed with cells before printing to produce cell-laden constructs. The dual-responsive hydrogel constructs demonstrated higher resolution and shape fidelity as well as better cell viability and proliferation than the thermoresponsive control. Moreover, the softer hydrogel (PUA3) with a low modulus (<1 kPa) could offer neural stem cells a tofu-like, stable, and inductive 3D microenvironment to proliferate and differentiate. We expect that the photo/thermoresponsive biodegradable polyurethane ink may offer unique rheological properties to contribute toward the custom-made bioprinting of soft tissues.

Self-Supporting Nanoclay as Internal Scaffold Material for Direct Printing of Soft Hydrogel Composite Structures in Air.

Three dimensional (3D) bioprinting technology enables the freeform fabrication of complex constructs from various hydrogels and is receiving increasing attention in tissue engineering. The objective of this study is to develop a novel self-supporting direct hydrogel printing approach to extrude complex 3D hydrogel composite structures in air without the help of a support bath. Laponite, a member of the smectite mineral family, is investigated to serve as an internal scaffold material for the direct printing of hydrogel composite structures in air. In the proposed printing approach, due to its yield-stress property, Laponite nanoclay can be easily extruded through a nozzle as a liquid and self-supported after extrusion as a solid. Its unique crystal structure with positive and negative charges enables it to be mixed with many chemically and physically cross-linked hydrogels, which makes it an ideal internal scaffold material for the fabrication of various hydrogel structures. By mixing Laponite nanoclay with various hydrogel precursors, the hydrogel composites retain their self-supporting capacity and can be printed into 3D structures directly in air and retain their shapes before cross-linking. Then, the whole structures are solidified in situ by applying suitable cross-linking stimuli. The addition of Laponite nanoclay can effectively improve the mechanical and biological properties of hydrogel composites. Specifically, the addition of Laponite nanoclay results in a significant increase in the Young's modulus of each hydrogel-Laponite composite: 1.9-fold increase for the poly(ethylene glycol) diacrylate (PEGDA)-Laponite composite, 7.4-fold increase for the alginate-Laponite composite, and 3.3-fold increase for the gelatin-Laponite composite.