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Double-network (DN) gels are unique mechanochemical materials owing to their structures that can be dynamically remodelled during use. The mechanical energy applied to DN gels is efficiently transferred to the chemical bonds of the brittle network, generating mechanoradicals that initiate the polymerisation of pre-loaded monomers, thereby remodelling the materials. To attain continuous remodelling or growth in response to repetitive mechanical stimuli, a sustainable supply of chemical reagents to such dynamic materials is essential. In this study, inspired by the vascular perfusion transporting nutrients to cells, we constructed a circulatory system for a continuous supply of chemicals to channel-containing DN hydrogels (c-DN gels). The perfusion of monomer solutions through the channel and permeability of the c-DN gels not only replenishes the monomers consumed by the polymerisation but also replenishes the water loss caused by the surface evaporation of hydrogel, thereby freeing the mechanochemical process of DN gels from the constraints of the underwater environment. The facile chemical supply enabled us to modulate the mechanical enhancement of the c-DN gel and attain muscle-like strengthening under repeated mechanical training in deoxygenated air. We also studied the kinetics of polymer growth and strengthening and deciphered unique features of mechanochemical reaction in DN gels including the extremely long-living radicals and delayed mechanical strengthening.

Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields., (© 2022. The Author(s).)

Understanding the physical principle that governs the stimuli-induced swelling and shrinking kinetics of hydrogels is indispensable for their applications. Here, we show that the shrinking and swelling kinetics of self-healing hydrogels could be intrinsically asymmetric. The structure frustration, formed by the large difference in the heat and solvent diffusions, remarkably slows down the shrinking kinetics. The plateau modulus of viscoelastic gels is found to be a key parameter governing the formation of structure frustration and, in turn, the asymmetric swelling and shrinking kinetics. This work provides fundamental understandings on the temperature-triggered transient structure formation in self-healing hydrogels. Our findings will find broad use in diverse applications of self-healing hydrogels, where cooperative diffusion of water and gel network is involved. Our findings should also give insight into the molecular diffusion in biological systems that possess macromolecular crowding environments similar to self-healing hydrogels.

Double network hydrogels (DN gels) composed of poly (2-acrylamido-2-methyl propanesulfonic acid) (PAMPS) as the brittle first network and poly ( N , N -dimethylacrylamide) (PDMA) as the ductile second network have been proven to be a substitute biomaterial for cartilage, with promising biocompatibility and low toxicity, when they are used as bulk materials. For their further applications as articular cartilages, it is essential to understand the biological reactions and adverse events that might be initiated by wear particles derived from these materials. In this study, we used DN gel micro-particles of sizes 4 μm and 10 μm generated by the grinding method to mimic wearing debris of DN gels. The biological responses to particles were then evaluated in a macrophage-cultured system and an inflammatory osteolysis murine model. Our results demonstrated that DN gel particles have the ability to activate macrophages and promote the expression of Tnf-α, both in vitro and in vivo . Furthermore, the implantation of these particles onto calvarial bone triggered local inflammation and bone loss in a mouse model. Our data reveal that the potential foreign body responses to the generated particles from artificial cartilage should receive more attention in artificial cartilage engineering with the goal of developing a safer biocompatible substitute.

Cation-π interactions in aqueous media are known to play critical roles in various biological activities. However, quantitative experimental information, such as the binding ratio of metal ions to aromatic groups, is hardly available due to the lack of a suitable test system and method. Herein, we proposed a hydrogel Donnan potential method to determine the binding ratio of metal ions to aromatic groups on polymer networks in aqueous media. In this method, we adopted recently developed poly(cation-π) hydrogels with a rich adjacent sequence of the cationic group and the aromatic group on the polymer network. A microelectrode technique (MET) is used to measure the Donnan potential of the poly(cation-π) hydrogels. From the Donnan potential, the binding ratios of various metal ions to aromatic groups are quantitatively determined for the first time.

Cancer recurrence can arise owing to rare circulating cancer stem cells (CSCs) that are resistant to chemotherapies and radiotherapies. Here, we show that a double-network hydrogel can rapidly reprogramme differentiated cancer cells into CSCs. Spheroids expressing elevated levels of the stemness genes Sox2, Oct3/4 and Nanog formed within 24 h of seeding the gel with cells from any of six human cancer cell lines or with brain cancer cells resected from patients with glioblastoma. Human brain cancer cells cultured on the double-network hydrogel and intracranially injected in immunodeficient mice led to higher tumorigenicity than brain cancer cells cultured on single-network gels. We also show that the double-network gel induced the phosphorylation of tyrosine kinases, that gel-induced CSCs from primary brain cancer cells were eradicated by an inhibitor of the platelet-derived growth factor receptor, and that calcium channel receptors and the protein osteopontin were essential for the regulation of gel-mediated induction of stemness in brain cancer cells., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Biological tissues usually have complex superstructures and elaborated functionalities. However, creating superstructures in soft and wet hydrogels is challenging because of the absence of effective approaches to control the molecular orientation. Here we introduce a method to create superstructures in photonic hydrogels comprising lamellar bilayers intercalated in the cross-linked polymer network. The orientation of lamellar bilayers in the photonic gel, which are sensitive to shear, is modulated by applying a gradient shear field on the precursor solution using a customized rheometer. The difference in orientation of lamellar bilayers leads to swelling mismatch in the radial direction, endowing the disk-shape hydrogel with a macroscopic flower-like shape with a central dome and an edge petal, along with a bright photonic color. By characterization of the swelling anisotropy of the radial profile, the shear rate required for the unidirectional orientation of lamellar bilayers was extracted. Moreover, a delayed polymerization experiment was designed to measure the lifetime of aligned lamellar bilayers, which reveals the domain size of lamellar bilayers in the precursor solution. Furthermore, we also demonstrated that the hydrogel flowers could fade and rebloom reversibly in response to external stimuli. This work presents a strategy to develop superstructures in hydrogels and sheds light on designing biomimetic materials with intricately architectural superstructure.

Soft and wet hydrogels have many similarities to biological tissues, though their mechanical fragility had been one of the biggest obstacles in biomedical applications. Studies and developments in double network (DN) hydrogels have elucidated how to create tough gels universally based on sacrificial bond principles and opened a path for biomedical application of hydrogels in regenerative medicine and artificial soft connective tissues, such as cartilage, tendon, and ligament, which endure high tension and compression. This review explores a universal toughening mechanism for and biomedical studies of DN hydrogels. Moreover, because the term sacrificial bonds has been mentioned often in studies of bone tissues, consisting of biomacromolecules and biominerals, recent studies of gel-biomineral composites to understand early-stage osteogenesis and to simulate bony sacrificial bonds are also summarized.

Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful. The low crystalline hydroxyapatite (HAp) of calcium-phosphate-hydroxide salt coated on the surface layer of the DN hydrogels induced spontaneous osteogenesis penetrating into the semi-permeable hydrogels to form a gel/bone composite layer. In this work, the 44 Ca isotope-doped HAp/DN hydrogel is implanted in a defect of rabbit femoral bone and the dynamic osteogenesis process at the gel/bone interface is analyzed by tracing the calcium isotope ratio using isotope microscopy. The synthetic HAp hybridized on the surface layer of DN gel dissolves rapidly in the first two weeks by inflammation, and then the immature bone with a gradient structure starts to form in the gel region, reutilizing the dissolved Ca ions. These results reveal, for the first time, that synthetic HAp is reutilized for osteogenesis. These facts help to understand the lifetime of bone absorbable materials and to elucidate the mechanism of spontaneous, non-toxic, but strong fixation of hydrogels to bones., (© 2020 Wiley-VCH GmbH.)

The high water content of hydrogels makes them important as synthetic biomaterials, and tuning the mechanical properties of hydrogels to match those of natural tissues without changing chemistry is usually difficult. In this study, we have developed a series of hydrogels with varied stiffness, strength, and toughness based on a combination of poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS), a strong acidic polyelectrolyte, and poly- N -(carboxymethyl)- N , N -dimethyl-2-(methacryloyloxy) ethanaminium) (PCDME), a polyzwitterion with a weak acidic moiety. We demonstrate that modifying the true molar ratio, R , of PCDME to PAMPS results in four unique categories of hydrogels with different swelling ratios and Young's moduli. When R < 1, a negatively charged polyelectrolyte gel (PE) is formed; when 1 < R < 3, a tough and viscoelastic polyelectrolyte complex gel (PEC) is formed; when 3 < R < 6.5, a conventional, elastic interpenetrating network gel (IPN) is formed; and when R > 6.5, a tough and stiff double-network gel (DN) is formed. Both the PEC and DN gels exhibit high toughness and fracture stress, up to 1.8 and 1.5 MPa, respectively. Importantly, the PEC gels exhibit strong recovery properties along with high toughness, distinguishing them from DN gels. Without requiring a change in chemistry, we can tune the mechanical response of hydrogels over a wide spectrum, making this a useful system of soft and hydrated biomaterials.

Chitin is a biopolymer, which has been proven to be a biomedical material candidate, yet the weak mechanical properties seriously limit their potentials. In this work, a chitin-based double-network (DN) hydrogel has been designed as a potential superficial repairing material. The hydrogel was synthesized through a double-network (DN) strategy composing hybrid regenerated chitin nanofiber (RCN)-poly (ethylene glycol diglycidyl ether) (PEGDE) as the first network and polyacrylamide (PAAm) as the second network. The hybrid RCN-PEGDE/PAAm DN hydrogel was strong and tough, possessing Young's modulus (elasticity) E 0.097 ± 0.020 MPa, fracture stress σ f 0.449 ± 0.025 MPa, and work of fracture W f 5.75 ± 0.35 MJ·m -3 . The obtained DN hydrogel was strong enough for surgical requirements in the usage of soft tissue scaffolds. In addition, chitin endowed the DN hydrogel with good bacterial resistance and accelerated fibroblast proliferation, which increased the NIH3T3 cell number by nearly five times within 3 days. Subcutaneous implantation studies showed that the DN hydrogel did not induce inflammation after 4 weeks, suggesting a good biosafety in vivo. These results indicated that the hybrid RCN-PEGDE/PAAm DN hydrogel had great prospect as a rapid soft-tissue-repairing material.

Negatively charged synthetic hydrogels have been known to facilitate various cellular responses including cell adhesion, proliferation, and differentiation; however, the molecular mechanism of hydrogel-dependent control of cell behavior remains unclear. Recently, we reported that negatively charged poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel induces chondrogenic differentiation of ATDC5 cells via novel protein reservoir function. In this study, we identified the cell adhesion molecules binding to PAMPS gels that act as mechanoreceptors. First, we performed a pull-down assay by particle gels using cell membrane proteins of ATDC5, and found that multiple membrane proteins bound to the PAMPS gel, whereas the uncharged poly(N,N'-dimethylacrylamide) gel as control did not bind to any membrane proteins. Western blot analysis indicated differential binding of integrin (ITG) isoforms to the PAMPS gel, in which the α4 isoform, but not α5 and αv, efficiently bound to the PAMPS gel. ITG α4 knockdown decreased cell spreading of ATDC5 on PAMPS gels, whereas the enhanced expression increased the behavior. Furthermore, ITG α4 depletion suppressed PAMPS gel-induced expression of bone morphogenic protein (BMP) 4 contributing to chondrogenic differentiation, in concordance with the reduction of ERK activation. These results demonstrated that membrane protein binding to PAMPS gels occurred in a charge-dependent manner, and that ITG α4 plays a crucial role in cell spreading on PAMPS gels and acts as a mechanoreceptor triggering cellular signaling leads to chondrogenic differentiation., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Inspired by bone tissues, we mineralized low crystalline hydroxyapatite (HAp) particles in double network (DN) hydrogels, and we observed that the HAp minerals toughen the gels. The contribution of dissipated energy from HAp minerals was over 500% higher than that from the polymer during tensile deformation. We elucidated that the amorphous parts in the HAp minerals break at deformation, acting as energy-dissipative sacrificial bonds. This result implies that not only brittle polymer networks but also minerals can provide sacrificial bonds to toughen soft materials.

Proteins of thermophiles are thermally stable in a high-temperature environment, adopting a strategy of enhancing the electrostatic interaction in hydrophobic media at high temperature. Herein, inspired by the molecular mechanism of thermally stable proteins, the synthesis of novel polymer materials that undergo ultrarapid, isochoric, and reversible switching from soft hydrogels to rigid plastics at elevated temperature is reported. The materials are developed from versatile, inexpensive, and nontoxic poly(acrylic acid) hydrogels containing calcium acetate. By the cooperative effects of hydrophobic interaction and ionic interaction, the hydrogels undergo significant spinodal decomposition and subsequent rubbery-to-glassy transition when heated to an elevated temperature. As a result, the gels exhibit super-rapid and significant hikes in stiffness, strength, and toughness by up to 1800-, 80-, and 20-folds, respectively, when the temperature is raised from 25 to 70 °C, while the volumes of the gels are almost unchanged. As a potential application, the performance of the materials as athletic protective gear is demonstrated. This work provides a pathway for developing thermally stiffened materials and may significantly broaden the scope of polymer applications., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Applying the double network principle to develop tough hydrogels with different polymer chemistries is important for the potential application of hydrogel materials. Synthesis of the two interpenetrated networks with contrasting structure and properties required for double networks usually involves a two-step polymerization process. In this work, we present a new method to synthesize tough double network hydrogels by post-physical crosslinking of linear semi-rigid polyelectrolytes entrapped in a chemically crosslinked neutral network. Owing to their semi-rigid structure, the linear polyelectrolytes form a brittle physical network above their overlap concentration in multi-valent ZrCl2O ion solutions without macroscopic phase separation within the flexible neutral network. The double network hydrogels thus prepared exhibit high modulus (∼1.7 MPa), strength (∼1.3 MPa), fracture strain (∼7.3), and strain energy density (∼5.9 MJ m-3), while containing over 80% water. These materials also exhibit modest self-healing ability (∼51% after 30 minutes), demonstrating an additional benefit of a physical sacrificial network. This method is simpler than the conventional two-step polymerization and could be applied to develop tough hydrogels from rigid polyelectrolytes, including biopolymers such as DNA, HA, and chondroitin sulfate.

Polyelectrolyte complexation between oppositely charged polyelectrolytes forms coacervates in dilute solutions and thin films in concentrated solutions. It is difficult to obtain macroscopically uniform bulk polyelectrolyte complex (PEC) materials, since the two polymers form insoluble complexes quickly at the contact interface during mixing, resulting in heterogeneous aggregates. Here, we succeeded in preparing bulk PEC materials based on desalting-induced polyelectrolyte complexation via viscoelastic phase separation. With a high ionic strength aqueous medium, a homogeneous and concentrated solution containing oppositely charged polyelectrolytes is prepared. Desalting of the counter-ions and co-ions of the solution through semi-permeable membranes induces viscoelastic phase separation of the solution to form a physical hydrogel with open pore structure. Regulating the charge ratio of the two oppositely charged polymers results in significant changes in the porous morphology and mechanical properties. The charge-balanced PEC hydrogels show unique properties including high toughness and self-recovery due to the reversible ionic associations. The porous yet tough properties of bulk PEC hydrogels makes them potential candidates for applications such as cell scaffolds.

Anisotropy of strain-induced internal damage in tough double network (DN) hydrogels is characterized by a sequence of two tensile experiments. Firstly, the virgin DN gels are subjected to a single biaxial loading-unloading cycle using various combinations of the two maximum strains λx,m and λy,m in the x- and y-directions (λx,m ≥ λy,m). Secondly, the rectangular subsamples, which are cut out from the unloaded specimens so that the long axis can have an angle (θ) relative to the larger pre-strain (x-)axis, are stretched uniaxially along the long axis. Directional internal damage caused by various types of pre-stretching is evaluated by comparing the loading curves of the virgin gels and the subsamples with various θ. The modulus reduction (ΔEθ) and strain-energy reduction (Dθ) are characterized as functions of λx,m, λy,m and θ. The anisotropy of damage increases with the anisotropy of imposed pre-strain field as well as λx,m, which is also observed in the anisotropic re-swelling behavior of the subsamples. The damage and the extensibility of the subsamples with θ = 0° increase with λy,m, and the damage of the subsamples with θ = 90° significantly increases with λx,m. These results reveal the presence of a pronounced damage cross-effect: a finite portion of the chain fractures in the first brittle network in one direction is caused by loading in the other orthogonal direction. This feature is in contrast to the very modest damage cross-effect in the silica reinforced elastomers, which show apparently similar stress-softening behavior but with a different origin. The strong damage cross-effect is a key feature of the internal fracture mechanism of the tough DN gels.

Living tissues, such as muscle, autonomously grow and remodel themselves to adapt to their surrounding mechanical environment through metabolic processes. By contrast, typical synthetic materials cannot grow and reconstruct their structures once formed. We propose a strategy for developing "self-growing" polymeric materials that respond to repetitive mechanical stress through an effective mechanochemical transduction. Robust double-network hydrogels provided with a sustained monomer supply undergo self-growth, and the materials are substantially strengthened under repetitive loading through a structural destruction-reconstruction process. This strategy also endows the hydrogels with tailored functions at desired positions by mechanical stamping. This work may pave the way for the development of self-growing gel materials for applications such as soft robots and intelligent devices., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Mechanically robust hydrogels are promising biomaterials as artificial supportive tissue. These applications require selective and robust bonding of the hydrogels to living tissue. Recently, we achieved strong in vivo bone bonding of a tough double network (DN) hydrogel, a potential material for use as artificial cartilage and tendon, by hybridizing osteoconductive hydroxyapatite (HAp) in the gel surface layer. In this work, we report micro patterning of HAp at the surface of the DN hydrogel for selective osteoconduction. Utilizing the dissolution of HAp in an acidic environment, the soft lithography technique using an acid gel stamp was adopted to form a high-resolution HAp pattern on the gel. The HAp-patterned gel showed well-regulated migration and adhesion of cells in vitro. Moreover, the HAp-patterned gel showed selective and robust bonding to the rabbit bone tissue in vivo. This HAp soft lithography technique allows for simple and quick preparation of tailor-made osteoconductive hydrogels and can be applied to other hydrogels for selective bone bonding. STATEMENT OF SIGNIFICANCE: Hydrogels, preserving large amount of water, have been studied for next-generation artificial soft tissues. However, fixation of hydrogels to living tissue was unsolved issue for clinical application. Recently, we achieved robust bonding of a tough double network gel to bone in vivo by coating of osteoconductive hydroxyapatite in the gel surface layer. For further progress for practical use, we report the micro patterning of HAp at the surface of the DN hydrogel by using soft lithography technique, to perform selective bonding to only objective area without unnecessary coalescence. The HAp lithography technique is simple, quick and non-toxic method to prepare tailor-made osteoconductive hydrogels and has universality of species of hydrogels., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Hydrogels have promising applications in diverse areas, especially wet environments including tissue engineering, wound dressing, biomedical devices, and underwater soft robotics. Despite strong demands in such applications and great progress in irreversible bonding of robust hydrogels to diverse synthetic and biological surfaces, tough hydrogels with fast, strong, and reversible underwater adhesion are still not available. Herein, a strategy to develop hydrogels demonstrating such characteristics by combining macroscale surface engineering and nanoscale dynamic bonds is proposed. Based on this strategy, excellent underwater adhesion performance of tough hydrogels with dynamic ionic and hydrogen bonds, on diverse substrates, including hard glasses, soft hydrogels, and biological tissues is obtained. The proposed strategy can be generalized to develop other soft materials with underwater adhesion., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unlabelled: The purpose of this study was to clarify fundamental mechanical properties and biological responses of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. This study discovered the following facts. First, these hydrogels had high mechanical performance comparable to the native cartilage tissue, and the mechanical properties were not affected by immersion in the saline solution for 12weeks. Secondly, the mechanical properties of the CS-DN gel were not significantly reduced at 12weeks in vivo, while the mechanical properties of the HA-DN gel were significantly deteriorated at 6weeks. Thirdly, the degree of inflammation around the HA-DN gel was the same as that around the negative control. The CS-DN gel showed a mild but significant foreign body reaction, which was significantly greater than the negative control and less than the positive control at 1week, while the inflammation was reduced to the same level as the negative control at 4 and 6weeks. Fourthly, these gels induced differentiation of the ATDC5 cells into chondrocytes in the culture with the insulin-free maintenance medium. These findings suggest that these tough hydrogels are potential biomaterials for future application to therapeutic implants such as artificial cartilage., Statement of Significance: The present study reported fundamental biomaterial properties of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. Both the HA- and CS-DN gels had high mechanical properties comparable to the cartilage tissue and showed the ability to induce chondrogenic differentiation of ATDC5 cells in vitro. They are potential biomaterials that may meet the requirements of artificial cartilage concerning the material properties. Further, these DN gels can be also applied to the implantable inducer for cell-free cartilage regeneration therapy., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to establish the efficacy of a therapeutic strategy for an articular cartilage defect using a poly-(2-acrylamido-2-methylpropanesulfonic acid)/poly-(N,N'-dimethyl acrylamide) DN gel in a sheep model. Seventeen mature sheep were used in this study. We created a 6.0-mm osteochondral defect in the femoral trochlea of the patellofemoral (PF) joint and the medial condyle of the tibiofemoral (TF) joint. A cylindrical DN gel plug was implanted into the defect of the right knee so that a vacant space of the planned depths of 2.0 mm in group I, 3.0 mm in group II, and 4.0 mm in group III were left. In the left knee, we created a defect with the same depth as the right knee. The regenerated tissues were evaluated with the O'Driscoll score and real-time PCR analysis of the cartilage marker genes at 12 weeks. The DN gel implanted defect of group II in the PF and TF joints was completely filled with a sufficient volume of the proteoglycan-rich tissue stained with Safranin-O. The score showed that group II was significantly greater than groups I and III when treated with DN gel in the PF joint (p = 0.0441, p = 0.0174, respectively) and in the TF joint (p = 0.0019, p = 0.0006, respectively). This study has clarified the short-term efficacy of the cartilage regeneration strategy using the DN gel in a sheep model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2159-2165, 2016., (© 2016 Wiley Periodicals, Inc.)

On implanting hydroxyapatite-mineralized tough hydrogel into osteochondral defects of rabbits, osteogenesis spontaneously penetrates into the gel matrix owing to the semi-permeablility of the hydrogel. The gradient layer (around 40 μm thick) contributes quite strong bonding of the gel to bone. This is the first success in realizing the robust osteointegration of tough hydrogels, and the method is simple and feasible for practical use., (© 2016 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Developing nonspecific, fast, and strong adhesives that can glue hydrogels and biotissues substantially promotes the application of hydrogels as biomaterials. Inspired by the ubiquitous adhesiveness of bacteria, it is reported that neutral polyampholyte hydrogels, through their self-adjustable surface, can show rapid, strong, and reversible adhesion to charged hydrogels and biological tissues through the Coulombic interaction., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Double-network hydrogels are one of the most promising candidates as artificial soft supporting tissues owing to their excellent mechanical performance, water storage capability, and biocompatibility. A double-network hydrogel consists of two contrasting polymer networks: rigid and brittle first network and soft and ductile second network. To satisfy this double-network requirement, polyelectrolyte and neutral polymer are suitable as the first and the second networks, respectively. Combination of these two networks gives rise to extraordinarily tough double-network hydrogel as a result of substantial internal fracture of the brittle first network at large deformation, which contributes to the energy dissipation. Therefore, the first network serves as the sacrificial bonds to toughen the material. The double-network principle is universal and many kinds of double-network hydrogels composed of various chemical species have been developed. Moreover, a molecular stent technology has been developed to synthesize the double-network hydrogels using neutral polymer network as the brittle first network. The sulfonic double-network hydrogel was found to induce spontaneous hyaline cartilage regeneration in vivo., (© IMechE 2015.)

A series of tough polyion complex hydrogels is synthesized by sequential homopolymerization of cationic and anionic monomers. Owing to the reversible interpolymer ionic bonding, the materials are self-healable under ambient conditions with the aid of saline solution. Furthermore, self-glued bulk hydrogels can be built from their microgels, which is promising for 3D/4D printing and the additive manufacturing of hydrogels., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Expanding undifferentiated induced pluripotent stem (iPS) cells in vitro is a basic requirement for application of iPS cells in both fundamental research and clinical regeneration. In this study, we intended to establish a simple, low cost and efficient method for the long-term self-renewal of mouse induced pluripotent stem (miPS) cells without using feeder-cells and adhesive proteins. Three scaffolds were selected for the long-term subculture of miPS cells over two months starting from passages 14 to 29: 1) a gelatin coated polystyrene (Gelatin-PS) that is a widely used scaffold for self-renewal of mouse embryonic stem (mES) cells; 2) a neutral hydrogel poly(N,N-dimethylacrylamide) (PDMAAm); and 3) a negatively charged hydrogel poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS). Each passaged miPS cells on these scaffolds were cryopreserved successfully and the revived cells showed high viability and proliferation. The passaged miPS cells maintained a high undifferentiated state on all three scaffolds and a high level of pluripotency by expressing differentiation markers in vitro and forming teratomas in SCID mice with derivatives of all three germ layers. Compared to Gelatin-PS, the two hydrogels exhibited much better self-renewal performance in terms of high proliferation rate and level of expression of undifferentiated gene markers as well as efficiency in pluripotent teratoma formation. Furthermore, the PNaAMPS hydrogel demonstrated a slightly higher efficiency and simpler operation of cell expansion than the PDMAAm hydrogel. To conclude, PNaAMPS hydrogel is an excellent feeder-free scaffold because of its simplicity, low cost and high efficiency in expanding a large number of miPS cells in vitro., (Copyright © 2012 John Wiley & Sons, Ltd.)

Based on the molecular stent concept, a series of tough double-network hydrogels (St-DN gels) made from the components of proteoglycan aggregates - chondroitin sulfate proteoglycans (1), chondroitin sulfate (2), and sodium hyaluronate (3) - are successfully developed in combination with a neutral biocompatible polymer. This work demonstrates a promising method to create biopolymer-based tough hydrogels for biomedical applications., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A long-term investigation of the shell shape and the basal morphology of barnacles grown on tough, double-network (DN) hydrogels and polydimethylsiloxane (PDMS) elastomer was conducted in a laboratory environment. The elastic modulus of these soft substrata varied between 0.01 and 0.47 MPa. Polystyrene (PS) (elastic modulus, 3 GPa) was used as a hard substratum control. It was found that the shell shape and the basal plate morphology of barnacles were different on the rigid PS substratum compared to the soft substrata of PDMS and DN hydrogels. Barnacles on the PS substratum had a truncated cone shape with a flat basal plate while on soft PDMS and DN gels, barnacles had a pseudo-cylindrical shape and their basal plates showed curvature. In addition, a large adhesive layer was observed under barnacles on PDMS, but not on DN gels. The effect of substratum stiffness is discussed in terms of barnacle muscle contraction, whereby the relative stiffness of the substratum compared to that of the muscle is considered as the key parameter.

Hydrogels attract great attention as biomaterials as a result of their soft and wet nature, similar to that of biological tissues. Recent inventions of several tough hydrogels show their potential as structural biomaterials, such as cartilage. Any given application, however, requires a combination of mechanical properties including stiffness, strength, toughness, damping, fatigue resistance and self-healing, along with biocompatibility. This combination is rarely realized. Here, we report that polyampholytes, polymers bearing randomly dispersed cationic and anionic repeat groups, form tough and viscoelastic hydrogels with multiple mechanical properties. The randomness makes ionic bonds of a wide distribution of strength. The strong bonds serve as permanent crosslinks, imparting elasticity, whereas the weak bonds reversibly break and re-form, dissipating energy. These physical hydrogels of supramolecular structure can be tuned to change multiple mechanical properties over wide ranges by using diverse ionic combinations. This polyampholyte approach is synthetically simple and dramatically increases the choice of tough hydrogels for applications.

Differentiation of embryoid bodies (EBs) into particular cell lineages has been extensively studied. There is an increasing interest in the effect of soft hydrogel scaffolds on the behavior of EBs, such as the initial adhesion, dynamic morphology change, and differentiation. In this study, without adding any other bioactive factors in the serum-containing medium, dynamic behaviors of mouse EBs loaded on the surface of hydrogels with different surface charge and chemical structures are investigated. EBs adhered quickly to negatively charged poly(sodium p-styrene sulfonate) (PNaSS) hydrogels, which facilitates EBs spreading, migration, and differentiation into three germ layers with high efficiency of cardiomyocytes differentiation, similar to that on gelatin coated polystyrene (PS) culture plate. While on neutral poly(acrylamide) (PAAm) hydrogels, EBs maintained the initial spherical morphology with high expression of pluripotency-related markers in the short culture periods, and then showed the significantly greater levels of selected endoderm markers after long-time culture. EBs cultured on negatively charged poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS) gels demonstrated the analogous behaviors with that of neutral PAAm gels at early differentiation phase (day 4+1). Then, their adhesion, spreading and differentiation were quite similar to that on negatively charged PNaSS gels. The correlation between surface properties of hydrogels and EBs differentiation was discussed.

We studied the ability of surfactants to reduce friction by boundary lubrication for a bulk hydrogel sliding on a solid surface in an aqueous solution. A piece of negatively charged polyelectrolyte hydrogel was slid across solid surfaces with various levels of hydrophobicity, using a strain-controlled parallel-plate rheometer in water. A dramatic reduction in the sliding friction, especially in the low velocity region, was detected by the addition of a surfactant to the water medium. This friction reduction was only observed in gel-solid friction but not in solid-solid friction, indicating that the soft and wet nature of the gel surface was crucial for this surfactant-induced friction reduction. This phenomenon reveals that surfactants can remain at the gel-mated interface, thus preventing direct interfacial interaction between the sliding surfaces, and significantly decreasing the frictional stress. The reported dramatic reduction in friction highlights the frictional characteristics of soft and wet hydrogel materials.

Background: Functional repair of articular osteochondral defects remains a major challenge not only in the field of knee surgery but also in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect., Methods: Twenty-five mature rabbits were used in this study. In the bilateral knees of each animal, we created an osteochondral defect having a diameter of 2.4-mm in the medial condyle. Then, in 21 rabbits, we implanted a DN gel plug into a right knee defect so that a vacant space of 1.5-mm depth (in Group I), 2.5-mm depth (in Group II), or 3.5-mm depth (in Group III) was left. In the left knee, we did not apply any treatment to the defect to obtain the control data. All the rabbits were sacrificed at 4 weeks, and the gross and histological evaluations were performed. The remaining 4 rabbits underwent the same treatment as used in Group II, and real-time PCR analysis was performed at 4 weeks., Results: The defect in Group II was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen. The Wayne's gross appearance and histology scores showed that Group II was significantly greater than Group I, III, and Control (p < 0.012). The relative expression level of type-2 collagen, aggrecan, and SOX9 mRNAs was significantly greater in Group II than in the control group (p < 0.023)., Conclusions: This study demonstrated that spontaneous hyaline cartilage regeneration can be induced in vivo in an osteochondral defect created in the femoral condyle by means of implanting the DN gel plug at the bottom of the defect so that an approximately 2-mm deep vacant space was intentionally left in the defect. This fact has prompted us to propose an innovative strategy without cell culture to repair osteochondral lesions in the femoral condyle.

We measured the gene expression, glycocalyx content, and surface properties of human coronary artery endothelial cells (HCAECs) cultured on poly(sodium p-styrene sulfonate) (PNaSS) hydrogels with various levels of elasticity ranged in 3-300 kPa. We found that all HCAECs reached confluence on these hydrogels while retaining the similar expression of EC-specific markers to that on polystyrene (PS), a widely used scaffold in cell culture in vitro. Real-time polymerase chain reaction (PCR) and glycosaminoglycan (GAG) assay showed that the amount of EC-specific glycocalyx secreted by HCAECs cultured on PNaSS gels was higher than that cultured on PS, and it increased with an increase of gel elasticity. Furthermore, the HCAECs cultured on PNaSS gels showed excellent property against platelet adhesion and lower surface friction than that on PS. The platelet adhesion and surface friction of HCAECs cultured on PNaSS gels also depend on the elasticity of gels. The largest amount of EC-specific glycocalyx, excellent blood compatibility, and the lowest friction were observed when the elastic modulus of the gel was larger than 60 kPa. Overall, HCAECs cultured on these hydrogels have better properties than those cultured on PS scaffold, demonstrating the PNaSS gels can be used as potential tissue engineering material for blood vessels.

Chondrocytes rapidly dedifferentiate into a more fibroblastic phenotype on a two-dimensional polystyrene substratum. This impedes fundamental research on these cells as well as their clinical application. This study investigated the redifferentiation behavior of dedifferentiated chondrocytes on a hydrogel substratum. Dedifferentiated normal human articular chondrocyte-knee (NHAC-kn) cells were released from the sixth-passage monolayer cultured on a polystyrene surface. These cells were then subcultured on a chemically crosslinked copolymer hydrogel, that is, poly(NaAMPS-co-DMAAm), and the cells thus obtained were used as the seventh-passage cultivation. Copolymer gels were synthesized from a negatively charged monomer, the sodium salt of 2-acrylamido-2-methyl-1-propanesulfonic acid (NaAMPS), and a neutral monomer, N,N-dimethylacrylamide (DMAAm). These gels were of different compositions because the molar fraction (F) of NaAMPS was varied (F = 0, 0.2, 0.4, 0.6, 0.8, and 1.0). The dedifferentiated NHAC-kn cells spontaneously redifferentiated to normal NHAC-kn cells on neutral (F = 0) and poly(NaAMPS-co-DMAAm) hydrogels of low charge density (F = 0.2). This was deduced from the cell morphology and expression of cartilage-specific genes and proteins. These results should enable us to establish a simple and efficient method for preparing large amounts of chondrocytes by cultivation on the surfaces of neutral and low-charge-density hydrogels.

A hydrogel with cylindrically symmetric structure at macroscopic scale has been developed by polymerization of a cationic monomer in the presence of a small amount of semi-rigid polyanion poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT) in a cylinder glass tube. The polyion complex radially aligns in the outer region of the synthesized cylinder gel. On the other hand, it orients in concentric and axial directions in the inner region. To the authors' knowledge, this is the first report of such millimeter-scale ordered structure developed in a polymeric hydrogel. We elucidate that homeotropic alignment on the glass wall is energetically favorable for the semi-rigid polyion complex, resulting in the radial orientation in the outer region. In the inner region, the oriented structures result from the monomer difffusion (due to the heterogeneous polymerization) that induces PBDT orientation perpendicular to the diffusion direction. The structured gels showing sensitive response of birefringence to external force are expected to find applications in optical sensors.

We investigated the behavior of chondrogenic ATDC5 cells on synthetic polymer gels with various charge densities: negatively charged poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) gel, neutral poly(dimethylacrylamide) (PDMAAm) gel, and copolymer gels of 2-acrylamido-2-methyl-1-propanesulfonic acid and dimethylacrylamide P(AMPS-co-DMAAm) with different compositions (molar fractions of AMPS, F=0.25, 0.5, 0.75). In insulin-free maintenance medium, the ATDC5 cells cultured on the highly negatively charged gels - PAMPS gel and the P(AMPS-co-DMAAm) copolymer gels (F=0.75) - spread and became confluent at day 7, and interestingly formed nodules at day 14, expressing type II collagen and proteoglycan. This result demonstrates that the highly negatively charged gels can induce chondrogenic differentiation of ATDC5 cells even in insulin-free maintenance medium, in which the ATDC5 cells cultured on the standard polystyrene dish cannot differentiate into chondrocytes. In insulin-supplemented differentiation medium, ATDC5 cells cultured on the PDMAAm gel made focal adhesions, rapidly aggregated and formed large nodules within 7 days, expressing significantly greater levels of type II collagen and proteoglycan than cells cultured on the polystyrene dish and the negatively charged gels. These results showed that the neutral gel accelerated chondrogenic differentiation of ATDC5 cells cultured in the differentiation medium. We suggest that the highly negatively charged PAMPS gel and the neutral PDMAAm gel are interesting biomaterials for cartilage tissue engineering as a scaffold with the potential to induce chondrogenic differentiation.

Ultrathin double-network hydrogels, which have super-high toughness under micro-scale thickness (elastic elongation epsilon(b) > 1000%, tensile strength sigma(b) > 2 MPa and tearing energy G approximately 600 J m(-2)), and solvent-triggered fast and high isometric stress generation, were synthesized by coupling the salt-controlled swelling process and polymer chain pre-reinforced technique.

Tough triple network (TN) hydrogels that facilitate cell spreading and proliferation and, at the same time, preserve high mechanical strength are synthesized by the introduction of a proper component of negatively charged moiety, poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS), on which cells proliferate, with neutral moiety, poly(N,N-dimethylacrylamide) (DMAAm), on which cells do not proliferate, as the third network component, to PNaAMPS/PDMAAm double network (DN) gels. For synthesizing the tough TN gels to support cell viability, the effect of charge density on the behaviors of three kinds of cells, bovine fetal aorta endothelial cells (BFAECs), human umbilical endothelial cells (HUVECs), and rabbit synovial tissue-derived fibroblast cells (RSTFCs) were systematically investigated on poly(NaAMPS-co-DMAAm) gels with different charge density. The charge density of the gels was tuned by changing the molar fraction (F) of negatively charged monomer in the copolymer hydrogels. Critical F, which corresponds to a critical value of the zeta potential (zeta), is observed for cell spreading and proliferation. The critical F for BFAECs and HUVECs proliferate to confluent is F = 0.4 (zeta = -20 mV), whereas the critical F for RSTFCs shifts to F = 0.7 (zeta = -28.5 mV). The effect of gel charge density on cell behavior is correlated well with the total adsorbed proteins and fibronectin. By applying these results, cell proliferation is successfully realized on the tough TN hydrogels without surface modification with any cell adhesive proteins or peptides. The results will substantially promote the application of tough hydrogels as soft and wet tissues., (2008 Wiley Periodicals, Inc.)

Double-network hydrogels (DN-gels) prepared from the combination of a moderately cross-linked anionic polyelectrolyte (PE) and an uncross-linked linear polymer solution (NP) exhibit mechanical properties such as fracture toughness that are intriguingly superior to that of their individual constituents. The scheme of double-network preparation, however, is not equally successful for all polyelectrolyte/neutral polymer pairs. A successful example is the combination of poly(2-acrylamido-2-methyl-1-propane sulfonic acid) (PAMPS) cross-linked network and linear polyacrylamide (PAAm), which results in DN-gels with fracture strength under compression approaching that of articular cartilage ( approximately 20 MPa). Small-angle neutron scattering was used to determine the thermodynamic interaction parameters for PAMPS and PAAm in water as a first step to elucidate the molecular origin responsible for this superior property. Measurements on PAMPS/PAAm DN-gels and their solution blend counterparts indicate that the two polymers interact favorably with each other while in water. This favorable PAMPS/PAAm interaction given by the condition chi(PE-NP) < chi(PE-water)

The study evaluated biological reaction of four types of novel double network gels in muscle and subcutaneous tissues, using implantation tests according to the international guideline. The implantation tests demonstrated that, although poly (2-acrylamide-2-metyl-propane sulfonic acid)/poly (N,N'-dimetyl acrylamide) (PAMPS/PDMAAm) gel induced a mild inflammation at 1 week, the degree of the inflammation significantly decreased into the same degree as that of the negative control at 4 and 6 weeks. This gel has a potential to be applied as artificial cartilage. In addition, Cellulose/Gelatin gel showed the same degree of inflammation as that of the negative control at 1 week, and then, showed a gradually absorbable property at 4 and 6 weeks. This gel has a potential to be applied as an absorbable implant. The PAMPS/polyacrylamide and Cellulose/PDMAAm gels induced a significant inflammation at each week. These DN gels are difficult to be applied as clinical implants in the current situation.

In this work we describe experiments designed to understand the human platelet adhesion to human umbilical vein endothelial cells (HUVECs) cultured on various kinds of chemically cross-linked anionic hydrogels, which were synthesized by radical polymerization. HUVECs could proliferate to sub-confluent or confluent on poly(acrylic acid) (PAA), poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS), and poly(sodium p-styrene sulfonate) (PNaSS) gels. The proliferation behavior was not sensitive to the cross-linker concentration of the gels. However, the platelet adhesion on the HUVECs cultured on these gels showed different behavior, as revealed by human platelet adhesion test in static conditions. Only a few platelets adhered on the HUVEC sheets cultured on PNaAMPS gels with 4 and 10mol% cross-linker concentrations, and completely no platelet adhered on the HUVEC sheets cultured on PNaSS gels with 4 and 10mol% cross-linker concentrations. On the other hand, a large number of platelets adhered on the HUVECs cultured on PAA gels with 1, 2mol% cross-linker concentrations and PNaAMPS gel with 2mol% cross-linker concentration. Furthermore, the study showed that promote of the glycocalyx of HUVECs with transforming growth factor-beta(1) (TGF-beta(1)) decreased platelet adhesion, and degrade the glycocalyx with heparinase I increased platelet adhesion. The results suggested that the glycocalyx of cultured HUVECs modulates platelet compatibility, and the amount of glycocalyx secreted by HUVECs dependents on the chemical structure and cross-linker concentration of gel scaffolds. This result should be applied to make the hybrid artificial blood vessel composes of gels and endothelial cells with high platelet compatibility.

The fracture energy G of double network (DN) gels, consisting of poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) as the first network and poly(acrylamide) (PAAm) as the second network, was measured by the tearing test as a function of the crack velocity V. The following results were obtained: (i) The fracture energy G ranges from 10(2) to approximately 10(3) J/m2, which is 100-1000 times larger than that of normal PAAm gels (10(0) J/m2) or PAMPS gels (10(-1) J/m2) with similar polymer concentrations to the DN gels. (ii) G shows weak dependence on the crack velocity V. (iii) G at a given value of V increases with decreasing of cross-linking density of the 2nd network. The measured values of G were compared with three theories that describe different mechanisms enhancing the fracture energy of soft polymeric systems. A mechanism relating to a heterogeneous structure of the DN gel is convincing for the remarkable large values of G.

Hydrogels of poly(2-hydroxyethyl methacrylate) (PHEMA) with well-defined polyelectrolyte brushes of poly(sodium 4-styrenesulfonate) (PNaSS) of various molecular weights were synthesized, keeping the distance between the polymer brushes constant at ca. 20 nm. The effect of polyelectrolyte brush length on the sliding friction against a glass plate, an electrorepulsive solid substrate, was investigated in water in a velocity range of 7.5 x 10(-5) to 7.5 x 10(-2) m/s. It is found that the presence of polymer brush can dramatically reduce the friction when the polymer brushes are short. With an increase in the length of the polymer brush, this drag reduction effect only works at a low sliding velocity, and the gel with long polymer brushes even shows a higher friction than that of a normal network gel at a high sliding velocity. The strong polymer length and sliding velocity dependence indicate a dynamic mechanism of the polymer brush effect.

It was found that when an aqueous solution of vinyl monomers is polymerized on a hydrophobic substrate, obvious heterogeneity occurs in the region of the interface. This substrate effect was observed on polytetrafluroethylene (Teflon), polypropylene (PP), polyethylene (PE), polystyrene (PS), and polyvinylchloride (PVC), but not on hydrophilic substrates. Compared with synthesis on hydrophilic surfaces, the surfaces of hydrogels synthesized on a hydrophobic substrate exhibit a larger degree of swelling, a lower surface coefficient of friction and elastic modulus, weaker interfacial adhesion, and reduced interaction with biological cells. This substrate effect has been observed for many types of aqueous monomer solutions. It was found that the above properties are related to the loosely cross-linked architecture, containing some graft-like polymer chains, that is formed on the gel surface when the gel is prepared on a hydrophobic substrate. To understand the mechanism of the substrate effect, two novel optical methods, electric speckle pattern interferometry (ESPI) and real-time laser sheet refraction (RT-LSR), were developed. It was found that oxygen trapped in the composite interface between the monomer solution and rough hydrophobic substrates played an important role in the substrate effect., (Copyright 2003 The Japan Chemical Journal Forum and Wiley Periodicals, Inc., Chem Rec 3: 40-50; 2003: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10048)

Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation towards glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future. [ABSTRACT FROM AUTHOR]

Numerous mechanically strong and tough soft materials comprising of polymer networks have been developed over the last two decades, motivated by new high-tech applications in engineering and bio-related fields. These materials are characterized by their dynamic complexities and large deformation behaviors. In this Review, we focus on how chain dynamics affects the large deformation and fracture behaviors of soft materials. To favor readers without a rheology background, first we review the linear rheology behaviors of several simple networks. We show that, by playing with the physical entanglement, chemical cross-linking, and physical association of the building polymers, a very rich panel of dynamic responses can be obtained. Then, we show examples of how chain dynamics affects the deformation and fracture behaviors of dually cross-linked hydrogels having chemical cross-linkers and physical bonds. We also provide examples on the unique deformation behavior of physical double-network gels made from triblock polymers. Thereafter, examples of the influence of chain dynamics on the crack initiation and growth behaviors are presented. We show that even for chemically cross-linked double-network hydrogels that exhibit elastic behaviors in a common deformation window, the chain dynamics influences the damage zone size at the crack tip. Finally, we conclude this Review by proposing several directions for future research. [ABSTRACT FROM AUTHOR]

The embedding of photonic crystals within stimuli‐responsive hydrogels has attracted tremendous interest because it provides new applications such as optical switches, displays, and sensors. However, the production of electrically tunable photonic hydrogels with a wide range of color tunability, fast electrical response, and high stability for repeated use is still challenging. Here, electrically tunable photonic hydrogels are fabricated using ultrahigh‐water‐content polyelectrolyte layered hydrogels composed of thousands of bilayer domain structures. The layered hydrogel exhibits versatile color tunability by applying an electric field parallel or perpendicular to the direction of the gel layers. The hydrogel exhibits homogeneous color tuning when a perpendicular electric field is applied, while it shows a large rainbow‐like electric‐optic response in the visible to near‐infrared region when a parallel electric field is applied. Additionally, by a simple method using patterned electrodes, a reflective display showing the designed characters is demonstrated and maintained for hours underwater without an external source of energy. Moreover, the electrically induced optical patterns can be erased, and the responsive photonic hydrogel shows excellent stability for repeated use. We anticipate that this study will provide the foundation for the development of responsive photonic hydrogels with new and large electro‐optical effects for future chromatic applications. [ABSTRACT FROM AUTHOR]

This study investigated whether hydrogels comprising hydrophilic cationic polymers have similar bactericidal effects. Bacteria were seeded on hydrogels and agar and their viability was assessed with time. Cationic hydrogels displayed bactericidal effects upon long‐term bacterial contact. Furthermore, we assessed the areal density of cationic monomer unit of the cationic hydrogels, water content, and the initial elastic modulus. We examined correlations between each factor and bacterial death ratios; consequently, the bacterial death ratios were strongly correlated with the areal density of cationic hydrogel monomers. Elastic energy (Wel) generated at the cytomembrane ion‐binding region and the cationic hydrogel and the cytomembrane interfacial energy (Wf) were estimated; consequently, Wel exceeded Wf at higher contact areas. The cationic hydrogel may extract cytomembranes with a reasonable adsorption area. Therefore, cationic hydrogels may be used as probes for ultrasonic echo to sterilize medical equipment. [ABSTRACT FROM AUTHOR]