Designing Tough Hydrogel Shells for Glucose Sensing.

Conventional hydrogel microcapsules often suffer from inadequate mechanical stability, hindering their use. Here, water-cored double-network (DN) hydrogel shells are designed, formed by polyacrylamide and calcium alginate networks using triple-emulsion templates. These DN hydrogel shells offer robust mechanical stability, optical transparency, and a precisely-defined cut-off threshold. The feasibility of this platform is demonstrated through the development of a fluorometric glucose sensor. Glucose oxidase is enclosed within the water core, while a pH-responsive fluorescent dye is incorporated into the DN shells. Glucose diffuses into the core through the DN shells, where the glucose oxidase converts glucose into gluconic acid, leading to pH reduction and a subsequent decrease in fluorescence intensity of DN shells. Additionally, the pH-sensitive colorant dissolved in the medium enables visual pH assessment. Thus, glucose levels can be determined using both fluorometric and colorimetric methods. Notably, the DN shells exhibit exceptional stability, enduring intense mechanical stress and cycles of drying and rehydration without leakage. Moreover, the DN shells act as effective barriers, safeguarding glucose oxidase against proteolysis by large disruptive proteins, like pancreatin. This versatile DN shell platform extends beyond glucose oxidase encapsulation, serving as a foundation for various capsule sensors utilizing enzymes and heterogeneous catalysts.

Polyelectrolyte-Mediated Modulation of Spatial Internal Stresses of Hydrogels for Complex 3D Actuators.

Hydrogel actuators with complex 3D initial shapes show numerous important applications, but it remains challenging to fabricate such actuators. This article describes a polyelectrolyte-based strategy for modulating small-scale internal stresses within hydrogels to construct complex actuators with tailored 3D initial shapes. Introducing polyelectrolytes into precursor solutions significantly enhances the volume shrinkage of hydrogel networks during polymerization, allowing us to modulate internal stresses. Photopolymerization of these polyelectrolyte-containing solutions through a mask produces mechanically strong hydrogel sheets with large patterned internal stresses. Consequently, these hydrogel sheets attain complex 3D initial shapes at equilibrium, in contrast to the planar initial configuration of 2D actuators. We demonstrate that these 3D actuators can reversibly transform into other 3D shapes (i.e., 3D-to-3D shape transformations) in response to external stimuli. Additionally, we develop a predictive model based on the Flory-Rehner theory to analyze the polyelectrolyte-mediated shrinking behaviors of hydrogel networks during polymerization, allowing precise modulation of shrinkage and internal stress. This polyelectrolyte-boosted shrinking mechanism paves a route to the fabrication of high-performance 3D hydrogel actuators.

Role of Polymer Concentration on the Release Rates of Proteins from Single- and Double-Network Hydrogels.

Controlled delivery of proteins has immense potential for the treatment of various human diseases, but effective strategies for their delivery are required before this potential can be fully realized. Recent research has identified hydrogels as a promising option for the controlled delivery of therapeutic proteins, owing to their ability to respond to diverse chemical and biological stimuli, as well as their customizable properties that allow for desired delivery rates. This study utilized alginate and chitosan as model polymers to investigate the effects of hydrogel properties on protein release rates. The results demonstrated that polymer properties, concentration, and crosslinking density, as well as their responses to pH, can be tailored to regulate protein release rates. The study also revealed that hydrogels may be combined to create double-network hydrogels to provide an additional metric to control protein release rates. Furthermore, the hydrogel scaffolds were also found to preserve the long-term function and structure of encapsulated proteins before their release from the hydrogels. In conclusion, this research demonstrates the significance of integrating porosity and response to stimuli as orthogonal control parameters when designing hydrogel-based scaffolds for therapeutic protein release.

Hybrid Phenol-Rhodamine Dye Based Mechanochromic Double Network Hydrogels with Tunable Stress Sensitivity.

Mechanochromic hydrogels, which can switch their color in response to the applied external force, have shown great potential in stress visualization and damage indication. However, the kinds of colors in the reported mechanochromic hydrogels are limited. It is challenging to develop mechanochromic hydrogels with new kinds of color changes. Herein, a kind of mechanochromic double network (DN) hydrogel is reported based on the hybrid phenol-rhodamine mechanophore. The hydrogels turn into orange color with an emission wavelength of around 566/574 nm in response to tensile and compressive stress. The DN hydrogels show great reversibility. The color of DN hydrogels vanishes slowly after releasing the stress. The stress sensitivity can be tailored by the crosslinking density and the mechanophore concentration of the first network. In addition, the influence of the pH on the mechanochromic properties of DN hydrogels is also studied. This study provides an insightful study in tuning the stress sensitivity in the mechanochromic hydrogel, which will be beneficial for the development of mechanochromic materials.

DNA Hydrogels in the Perspective of Mechanical Properties.

Tailoring the mechanical properties has always been a key to the field of hydrogels in terms of different applications. Particularly, DNA hydrogels offer an unambiguous way to precisely tune the mechanical properties, largely on account of their programmable sequences, abundant responding toolbox, and various ligation approaches. In this review, DNA hydrogels from the perspective of mechanical properties, from a synthetic standpoint to different applications, are introduced. The relationship between the structure and their mechanical properties in DNA hydrogels and the methods of regulating the mechanical properties of DNA hydrogels are specifically summarized. Furthermore, several recent applications of DNA hydrogels in relation to their mechanical properties are discussed. Benefiting from the tunability and flexibility, rational design of mechanical properties in DNA hydrogels provided unheralded interest from fundamental science to extensive applications.

A Glucose Biosensor Based on Phosphorescence Lifetime Sensing and a Thermoresponsive Membrane.

The adoption of existing continuous glucose monitors (CGMs) is limited by user burden. Herein, a design for a glucose biosensor with the potential for subcutaneous implantation, without the need for a transcutaneous probe or affixed transmitter, is presented. The design is based on the combination of an enzyme-driven phosphorescence lifetime-based glucose-sensing assay and a thermoresponsive membrane anticipated to reduce biofouling. The metalloporphyrin, Pd meso-tetra(sulfophenyl)-tetrabenzoporphyrin ([PdPh4 (SO3 Na)4 TBP]3 , HULK) as well as glucose oxidase (GOx) are successfully incorporated into the UV-cured double network (DN) membranes by leveraging electrostatic interactions and covalent conjugation, respectively. The oxygen-sensitive metalloporphyrin is incorporated at different levels within the DN membranes. These HULK-containing membranes retain the desired thermosensitivity, as well as glucose diffusivity and primary optical properties of the metalloporphyrin. After subsequently modifying the membranes with GOx, glucose-sensing experiments reveal that membranes prepared with the lowest GOx level exhibit the expected increase in phosphorescent lifetime for glucose concentrations up to 200 mg dL-1 . For membranes prepared with relatively higher GOx, oxygen-limited behavior is considered the source of diminished sensitivity at higher glucose levels. This proof-of-concept study demonstrates the promising potential of a biosensor design integrating a specific optical biosensing chemistry into a thermoresponsive hydrogel membrane.

Janus Nanoparticle Coupled Double-Network Hydrogel.

For double network (DN) hydrogels, their performance can be tuned by adjusting the interaction between their two networks. A novel DN hydrogel toughening approach is proposed by employing Janus nanoparticles (JNs) as crosslinkers to gain a conjoined-network hydrogel. First, a kind of JNs modified by amino groups and quaternary ammonium salt is synthesized, named R3 N+ -JN-NH2 . The DN hydrogel is fabricated based on ionic coordination between calcium chloride (CaCl2 ) and sodium alginate (Alg), as well as covalent (benzoic imine) between glycol chitosan (GC) and benzaldehyde-capped poly(ethylene oxide) (BzCHO-PEO-BzCHO). Based on the same covalent and ionic dynamic crosslinking mechanism, the added R3 N+ -JN-NH2 interacts with two networks to promote crosslinking to form a dually crosslinked structure. The R3 N+ -JN-NH2 effectively provides more energy dissipation, and the hydrogel with conjoined networks shows better compression resistance.

Strong and Reversible Covalent Double Network Hydrogel Based on Force-Coupled Enzymatic Reactions.

Biological load-bearing tissues are strong, tough, and recoverable under periodic mechanical loads. However, such features have rarely been achieved simultaneously in the same synthetic hydrogels. Here, we use a force-coupled enzymatic reaction to tune a strong covalent peptide linkage to a reversible bond. Based on this concept we engineered double network hydrogels that combine high mechanical strength and reversible mechanical recovery in the same hydrogels. Specifically, we found that a peptide ligase, sortase A, can promote the proteolysis of peptides under force. The peptide bond can be re-ligated by the same enzyme in the absence of force. This allows the sacrificial network in the double-network hydrogels to be ruptured and rebuilt reversibly. Our results demonstrate a general approach for precisely controlling the mechanical and dynamic properties of hydrogels at the molecular level.

Hybrid 3D Printing of Synthetic and Cell-Laden Bioinks for Shape Retaining Soft Tissue Grafts.

Despite recent advances in clinical procedures, the repair of soft tissue remains a reconstructive challenge. Current technologies such as synthetic implants and dermal flap autografting result in inefficient shape retention and unpredictable aesthetic outcomes. 3D printing, however, can be leveraged to produce superior soft tissue grafts that allow enhanced host integration and volume retention. Here, a novel dual bioink 3D printing strategy is presented that utilizes synthetic and natural materials to create stable, biomimetic soft tissue constructs. A double network ink composed of covalently crosslinked poly(ethylene) glycol and ionically crosslinked alginate acts as a physical support network that promotes cell growth and enables long-tersm graft shape retention. This is coupled with a cell-laden, biodegradable gelatin methacrylate bioink in a hybrid printing technique, and the composite scaffolds are evaluated in their mechanical properties, shape retention, and cytotoxicity. Additionally, a new shape analysis technique utilizing CloudCompare software is developed that expands the available toolbox for assessing scaffold aesthetic properties. With this dynamic 3D bioprinting strategy, complex geometries with robust internal structures can be easily modulated by varying the print ratio of non-degradable to sacrificial strands. The versatility of this hybrid printing fabrication platform can inspire the design of future multi-material regenerative implants.

A Highly Elastic and Reversibly Stretchable All-Polymer Supercapacitor.

Multiple stretchability has never been demonstrated as supercapacitors because the hydrogel used cannot fully recover after being heavily deformed. Now, a highly reversibly stretchable all-polymer supercapacitor was fabricated using a developed double network hydrogel (DN hydrogel) as electrolyte and pure polypyrrole (PPy) as electrode. The DN hydrogel provides excellent mechanical properties, which can be stretched up to 500 % many times and then restore almost 100 % of the original length. To fabricate the fully recoverable stretchable supercapacitor, we annealed a free-standing pure conducting polymer film as electrode so that the electrodes induced retardance is minimized. The as-fabricated DN hydrogel/pure conducting polymer supercapacitors can be perfectly recovered from 100 % strain with almost no residual deformation left and the electrochemical performance can be maintained even after 1000 stretches (but not bending).

Self-Sorting Double-Network Hydrogels with Tunable Supramolecular Handedness and Mechanical Properties.

Self-sorting, simultaneous, and orthogonal operations during the self-assembly of complex mixtures are commonly observed for biological species but rare in artificial systems. In this study, we designed two gelators (LPF and LPFEG) containing the same chiral phenylalanine core but different achiral peripheral substituents to give hydrogels with opposite supramolecular handedness. When the two hydrogels were mixed, double-network nanofibers with opposite handedness were formed by spontaneous high-order organization and self-sorting of the two gelators. The chiroptical activity of the double-network hydrogels could be tuned by varying the molar ratio of LPF and LPFEG in the mixture, thus showing that the two gelators were highly independent of each other. Enhanced mechanical properties were observed for the interpenetrating networks when the LPF/LPFEG molar ratio was 3:7, with a more than fourfold increase in both the storage (G') and loss modulus (G'') relative to those of the individual hydrogels.

Enzyme-Mineralized PVASA Hydrogels with Combined Toughness and Strength for Bone Tissue Engineering.

Enzymatic mineralization is an advanced mineralization method that is often used to enhance the stiffness and strength of hydrogels, but often accompanied by brittle behavior. Moreover, the hydrogel systems with dense networks currently used for enzymatic mineralization are not ideal materials for bone repair applications. To address these issues, two usual bone repair hydrogels, poly(vinyl alcohol) (PVA) and sodium alginate (SA), were selected to form a double-network structure through repeated freeze-thawing and ionic cross-linking, followed by enzyme mineralization. The results demonstrated that both enzymatic mineralization and double-network structure improved the mechanical and biological properties and even exhibited synergistic effects. The mineralized PVASA hydrogels exhibited superior comprehensive mechanical properties, with a Young's modulus of 1.03 MPa, a storage modulus of 103 kPa, and an equilibrium swelling ratio of 132%. In particular, the PVASA hydrogel did not suffer toughness loss after mineralization, with a high toughness value of 1.86 MJ/m3. The prepared hydrogels also exhibited superior biocompatibility with a cell spreading area about 13 times that of mineralized PVA. It also effectively promoted cellular osteogenic differentiation in vitro and further promoted the formation of new bone in the femur defect region in vivo. Overall, the enzyme-mineralized PVASA hydrogel demonstrated combined strength and toughness and great potential for bone tissue engineering applications.

An Environment-Tolerant Ion-Conducting Double-Network Composite Hydrogel for High-Performance Flexible Electronic Devices.

High-performance ion-conducting hydrogels (ICHs) are vital for developing flexible electronic devices. However, the robustness and ion-conducting behavior of ICHs deteriorate at extreme temperatures, hampering their use in soft electronics. To resolve these issues, a method involving freeze-thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network (DN) ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol) (PMP DN ICH) system. The well-designed ICH exhibits outstanding ionic conductivity (63.89 mS cm-1 at 25 °C), excellent temperature resistance (- 60-80 °C), prolonged stability (30 d at ambient temperature), high oxidation resistance, remarkable antibacterial activity, decent mechanical performance, and adhesion. Additionally, the ICH performs effectively in a flexible wireless strain sensor, thermal sensor, all-solid-state supercapacitor, and single-electrode triboelectric nanogenerator, thereby highlighting its viability in constructing soft electronic devices. The highly integrated gel structure endows these flexible electronic devices with stable, reliable signal output performance. In particular, the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm-2 (current density, 1 mA cm-2) and excellent environmental adaptability. This study paves the way for the design and fabrication of high-performance multifunctional/flexible ICHs for wearable sensing, energy-storage, and energy-harvesting applications.

Analysis of Fatigue Crack Nucleation in Double-Network Hydrogels.

Hydrogel-based devices commonly have a high demand for material durability when subjected to prolonged or cyclic loads. To extend their service life, it is crucial to have a deep understanding of the fatigue mechanisms of hydrogels. It is well-known that double-network (DN) hydrogels are characterized by high strength and toughness and are thus recognized as a promising candidate under load-bearing conditions. However, the existing studies in the literature mainly focus on their resistant capability to fatigue crack growth, while the underlying mechanisms of fatigue crack nucleation are still inconclusive. This work aims to bridge this knowledge gap by formulating a fatigue life predictor for DN hydrogels within the framework of configurational mechanics to elucidate the underlying mechanisms governing fatigue crack nucleation. The fatigue life predictor for DN hydrogels is derived from the configurational stress by incorporating the corresponding constitutive models and the thermodynamic evolution laws for microdamage mechanisms and material viscoelasticity. With the developed fatigue predictor, the effect of the microdamage mechanism on fatigue is elucidated, i.e., the internal damage of the sacrificial network can improve the fatigue life of DN hydrogels. The fatigue life predictor is also adopted to evaluate the effects of some other factors on the fatigue crack nucleation, such as the loading rate, pre-stretching treatment, and water diffusion, identifying feasible loading profiles that could improve material durability. Overall, the theoretical framework and the modeling results in this work are expected to shed light on unveiling the fatigue mechanisms of DN hydrogels and advance the design of hydrogel-based devices.

Digital light processing printed hydrogel scaffolds with adjustable modulus.

Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 µm) and broad modulus adjusting capability (15.8-345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.

Mechanical and biological behavior of double network hydrogels reinforced with alginate versus gellan gum.

Alginate and gellan gum have both been used by researchers as reinforcing networks to create tough and biocompatible polyethylene glycol (PEG) based double network (DN) hydrogels; however, the relative advantages and disadvantages of each approach are not understood. This study directly compares the mechanical and biological properties of polyethylene glycol di-methacrylate (PEGDMA) hybrid DN hydrogels reinforced with either gellan gum or sodium alginate using PEGDMA concentrations from 10 to 20 wt% and reinforcing network concentrations of 1 and 2 wt%. The findings demonstrate that gellan gum reinforcement is more effective at increasing the strength, stiffness, and toughness of PEGDMA DN hydrogels. In contrast, alginate reinforcement yields DN hydrogels with greater stretchability compared to gellan gum reinforced PEGDMA. Furthermore, separate measurements of toughness via unnotched work of rupture testing and notched fracture toughness testing showed a strong correlation of these two properties for a single reinforcing network type, but not across the two types of reinforcing networks. This suggests that additional notched fracture toughness experiments are important for understanding the full mechanical response when comparing different tough DN hydrogel systems. Regarding the biological response, after conjugation of matrix protein to the surface of both materials robust cell attachment and spreading was supported with higher yes associated protein (YAP) nuclear expression observed in populations adhering to the stiffer gellan gum-PEGDMA material. This study provides valuable insights regarding how to design double network hydrogels for specific property requirements, e.g., for use in biomedical devices, as scaffolding for tissue engineering, or in soft robotic applications.

Double network hydrogels: Design, fabrication, and application in biomedicines and foods.

Research on the design, fabrication, and application of double network (DN) hydrogels, assembled from pairs of polymers, has grown recently due to their unique structural, physicochemical, and functional properties. DN hydrogels can be designed to exhibit a broader range of functional attributes than single network (SN) ones, which extends their applications in various fields. There has been strong interest in the development of biopolymer DN hydrogels because of their environmental, sustainability, and safety benefits. However, there is limited knowledge on the formation and application of these novel materials. This article reviews the principles underlying the design and fabrication of hydrogels using different crosslinking approaches, including covalent and/or non-covalent bonding, and the formation mechanisms, network structures, and functional attributes of different DN hydrogels. The impact of polymer composition, structural organization, and bonding on the mechanical and functional properties of DN hydrogels is reviewed. Potential applications of these hydrogels are highlighted, including in tissue engineering, biomedicines, and foods. The functional attributes of DN hydrogels can be tailored to each of these applications by careful selection of the biopolymers and crosslinking mechanisms used to assemble them. Finally, areas where further research are needed to overcome the current limitations of DN hydrogels are highlighted.

Enhanced Rupture Force in a Cut-Dispersed Double-Network Hydrogel.

The Kirigami approach is an effective way to realize controllable deformation of intelligent materials via introducing cuts into bulk materials. For materials ranging from ordinary stiff materials such as glass, ceramics, and metals to soft materials, including ordinary hydrogels and elastomers, all of them are all sensitive to the presence of cuts, which usually act as defects to deteriorate mechanical properties. Herein, we study the influence of the cuts on the mechanical properties by introducing "dispersed macro-scale cuts" into a model tough double network (DN) hydrogel (named D-cut gel), which consists of a rigid and brittle first network and a ductile stretchable second network. For comparison, DN gels with "continuous cuts" having the same number of interconnected cuts (named C-cut gel) were chosen. The fracture tests of D-cut gel and C-cut gel with different cut patterns were performed. The fracture observation revealed that crack blunting occurred at each cut tip, and a large wrinkle-like zone was formed where the wrinkles were parallel to the propagation direction of the cut. By utilizing homemade circular polarizing optical systems, we found that introducing dispersed cuts increases the rupture force by homogenizing the stress around the crack tip surrounding every cut, which reduces stress concentration in one certain cut. We believe this work reveals the fracture mechanism of tough soft materials with a kirigami cut structure, which should guide the design of advanced soft and tough materials along this line.

One-Step Soaking Strategy toward Anti-Swelling Hydrogels with a Stiff "Armor".

Double-network (DN) hydrogels consisting of noncovalent interacting networks are highly desired due to their well-controlled compositions and environmental friendliness, but the low water resistance always impairs their mechanical strength. Here, an anti-swelling hydrogel possessing the core/shell architecture through rational regulation of multiple weak noncovalent interactions is prepared. A composite hydrogel consists of chitosan (CS) and poly(N-acryloyl 2-glycine) (PACG), readily forming the shell-structured DN hydrogel after soaking in a FeCl3 solution because of in situ formation of chain entanglements, hydrogen bonds, and ionic coordination. The produced DN hydrogels exhibit excellent anti-swelling behaviors and mechanical durability for over half a year, even in some strict situations. Taking the merits of noncovalent bonds in adjustability and reversibility, the swelling property of these hydrogels can be easily customized through control of the ion species and concentrations. A dynamically reversible transition from super-swelling to anti-swelling is realized by breaking up and rebuilding the metal-coordination complexes. This facile but efficient strategy of turning the noncovalent interactions and consequently the mechanics and anti-swelling properties is imperative to achieve the rational design of high-performance hydrogels with specific usage requirements and expand their applicability to a higher stage.