Temperature and Redox‐Responsive Hydrogels Based on Nitroxide Radicals and Oligoethyleneglycol Methacrylate

A temperature and redox‐responsive polymer hydrogel is constructed by randomly incorporating 2,2,6,6‐tetramethyl‐1‐piperidinyloxy‐methacrylate (TEMPO) stable nitroxide radicals and oligoethyleneglycol methacrylate (OEGMA) groups in a polymer network. TEMPO can be reversibly oxidized into an oxoammonium cation (TEMPO⁺) providing the redox‐responsive properties while the lower critical solubility temperature (LCST) of OEGMA results in temperature‐responsive properties. Since a rather low amount of di(ethylene glycol) dimethacrylate (OEGMA₂) is used to chemically crosslink the polymer network, the accordingly formed hydrogels obtained after swelling with water consist of microgel particles with entangled polymer chains that are not chemically crosslinked. By varying the amount of TEMPO in the polymer network, it is demonstrated that the radical form of TEMPO aggregates into hydrophobic domains acting as physical crosslinking nodes in the hydrogels and further increasing the cohesion between microgel particles. Increasing the temperature results in two opposite effects on the solubility of TEMPO and OEGMA units. The oxidation of TEMPO into TEMPO⁺ also results in a deep change in the hydrogel properties since TEMPO⁺ units are essentially hydrophilic and do not aggregate into physical crosslinking nodes.     

Microstructure‐Controllable Graphene Oxide Hydrogel Film Based on a pH‐Responsive Graphene Oxide Hydrogel

A graphene oxide hydrogel (GOH) is fabricated via suspending the graphene oxide (GO) in water without any additional processing steps. At the hydrogel/air interface, a well‐defined hydrogel membrane forms once the solvent is removed by vacuum drying. The microstructure of the resulting GOH film can be tailored by different dehydration approaches, as well as by varying the GO concentration in the hydrogel. This GOH exhibited pH‐responsiveness and good mechanical properties. Meanwhile, the GOH presented good adsorption capacity to the organic dye rhodamine B and anionic chromate Cr₂O₇^2?. This GOH may find great potential in many fields, such as wastewater treatment, biodetection, etc.     

Mechanical and Chemical Analysis of Gelatin‐Based Hydrogel Degradation

The interrelated effect of environmental pH and temperature, gelatin backbone modification and content on the tensile and degradative property of interpenetrating networks (IPNs) containing gelatin and poly(ethylene glycol) diacrylate (PEGdA) was examined. Either increasing the PEGdA content or modifying the gelatin backbone with PEG‐monoacetate ester and/or polyanions decreased the IPN elasticity at ambient room temperature (rt). Under an aqueous environment of varying pH levels and elevated temperature, the degradation of IPN tensile properties was further accelerated. IPNs showed an enhanced elasticity and strength when compared to glutaraldehyde‐fixed gelatin hydrogels. Under an aqueous condition, IPNs showed a wider range of degradation products than hydrogels cross‐linked with glutaraldehyde, as characterized with gel permeation chromatography. The nature of IPN degradation products was independent of the type of gelatin backbone modification. The presence of loaded drug, chlorohexidine digluconate, which was found to interact with PEG‐monoacetate esters of the modified gelatin backbone, resulted in unique degradation products. The tensile and chemical degradation of IPNs is a complex interrelationship of the environmental condition, time, and material modification.

Stress‐strain curves of some IPNs studied here.     

Photoresponsive Coumarin‐Based Supramolecular Hydrogel for Controllable Dye Release

Recently, photoresponsive hydrogels have attracted increasing interest due to their ability to provide precise spatial and temporal control of drug release. Herein, a new kind of coumarin‐based photoresponsive supramolecular hydrogelator without conventional gelation motif is designed and synthesized through a facile one‐pot method. The gelation process, photoresponsiveness, self‐assembly morphology, self‐assembly mechanism, and release kinetics are fully investigated by various characterization methods (e.g., scanning electron microscopy, single crystal X‐ray diffraction, high pressure liquid chromatography, UV–vis spectroscopy). Furthermore, encapsulated methyl violet dye molecules can be precisely released from the hydrogel by manipulating photoirradiation time. The study reveals that the coumarin‐based photoresponsive hydrogel holds great potential as soft materials for controllable drug release.     

Clickable Poly(ethylene glycol)‐Microsphere‐Based Cell Scaffolds

Clickable poly(ethylene glycol) (PEG) derivatives are used with two sequential aqueous two‐phase systems to produce microsphere‐based scaffolds for cell encapsulation. In the first step, sodium sulfate causes phase separation of the clickable PEG precursors and is followed by rapid geleation to form microspheres in the absence of organic solvent or surfactant. The microspheres are washed and then deswollen in dextran solutions in the presence of cells, producing tightly packed scaffolds that can be easily handled while also maintaining porosity. Endothelial cells included during microsphere scaffold formation show high viability. The clickable PEG‐microsphere‐based cell scaffolds open up new avenues for manipulating scaffold architecture as compared with simple bulk hydrogels.

     

A Novel Double‐Network,Self‐Healing Hydrogel Based on Hydrogen Bonding and Hydrophobic Effect

In this paper, acrylamide is used as a hydrophilic monomer, and octadecyl methacrylate (C18) and polyurethane (PU) monomers are used as hydrophobic monomers. In an aqueous solution containing mixed surfactants of cetyl trimethylammonium bromide and sodium dodecyl sulfate, a series of composite physical hydrogels with dual network structures are synthesized using these three monomers through in situ micelle copolymerization. The results indicate that, with the increase in PU content (<0.08 g), the thermal stability and mechanical properties (stretching and compressive) of the composite gel are enhanced, while the swelling performance becomes poorer. Furthermore, it can heal at room temperature and the self‐healing property approaches 88% of that of the original sample after 60 min. Additionally, the self‐healing efficiency shows a downward trend with the increase in the amount of PU, which is mainly related to the recovery efficiency of the network chain (polyacrylamide (PAAM) chain and PU chain) and the decrease in the mobility of C18. By constructing the double‐crosslinked network, the design and preparation of polymer hydrogels with high stretching capability, good elasticity and self‐healing performance provides a new approach to preparing hydrogels with excellent properties.     

Porous Semi‐Interpenetrating Hydrogel Networks Based on Dextran and Polyacrylamide With Superfast Responsiveness

AAm was free‐radical polymerized at various temperatures in the presence of N,N'‐methylenebisacrylamide as a cross‐linker and dextran resulting in novel Dx/PAAm semi‐IPNs. The structure and morphology of networks were investigated by means of FTIR, DSC, and ESEM. In comparison to the PAAm network, the interior network structures of the novel semi‐IPNs prepared at ?18 °C exhibit a heterogeneous morphology consisting of pores of sizes about 80 µm, while those formed at +5 and +25 °C have pores with sizes about 3 µm. The Dx/PAAm semi‐IPNs exhibited higher swelling ratios, than those without Dx, irrespective of the gel preparation temperature. Moreover, Dx/PAAm semi‐IPN hydrogels formed at ?18 °C attain the equilibrium state in water within 15 s.

     

Ionic‐Strength‐ and pH‐Responsive Poly[acrylamide‐co‐(maleic acid)] Hydrogel Nanofibers

A novel acrylamide/maleic acid copolymer [P(AM‐MA)] hydrogel nanofibrous membrane with a fiber diameter of ca. 120 nm is prepared by electrospinning an aqueous P(AM‐MA) solution with diethylene glycol as crosslinker, followed by a heat‐induced esterification crosslinking reaction at 145 °C. This hydrogel nanofiber can maintain a fiber form, but becomes distorted and merges to form many physical crosslinking points after immersion in water. The P(AM‐MA) hydrogel nanofibers are sensitive to external stimuli ionic strength and pH. Their water‐swelling ratio decreases with increasing solution ionic strength, and it shows a characteristic two‐step increase at pH = 2.5 and 8.5 in response to the increase of solution pH. The maximum water‐swelling ratios of the P(AM‐MA) hydrogel nanofibers are 18.1 and 22.5 g · g^?1 in a solution of 0.05 mol · dm^?3 ionic strength and in an aqueous solution of pH 11, respectively.

     

Strong Cationic Radical Initiator‐Based Design of a Thermoresponsive Hydrogel Showing Drastic Volume Transition

In this study, a millimeter‐sized thermoresponsive poly(N‐isopropylacrylamide) (PNIPAAm) gel is prepared by free radical polymerization using 2,2′‐azobis‐[2‐(1,3‐dimethyl‐4,5‐dihydro‐1H‐imidazol‐3‐ium‐2‐yl)]propane triflate (ADIP), a radical initiator possessing a strong cationic group that is newly developed. By comparing this gel with a PNIPAAm gel prepared using a conventional radical initiator, 2,2′‐azobisisobutyronitrile, the following properties are found: 1) the cationic residue of ADIP is introduced in the gel, and 2) the PNIPAAm gel prepared using ADIP exhibits a discontinuous volume transition as a function of temperature and rapid shrinking in response to temperature jump. This thermoresponsive behavior is attributed to the low polymer fraction in the gel prepared using ADIP. The ADIP‐based design of the thermoresponsive hydrogel investigated herein may contribute to the design of functional soft materials.     

Gallol‐Tethered Injectable AuNP Hydrogel with Desirable Self‐Healing and Catalytic Properties

Injectable self‐healing hydrogels have drawn growing attention for their extensive applications in biomedical fields. Hydrogels containing nanoparticles also exhibit promising potentials in catalysis, wastewater treatment, and organic synthesis. Inspired by the multifunction of gallol presented herein, a simple one‐pot method to produce a gallol‐tethered gelatin hydrogel via Schiff base under oxidizing conditions using various oxidants is presented. The hydrogels prepared by NaIO₄‐induced cross‐linking present a high self‐healing rate (up to 84.5%), injectable ability, tunable mechanical property, flexible viscoelasticity, and macroporous structure owing to the combination of covalent cross‐linking and supramolecular interactions. HAuCl₄ contributes to the 3D structure formation of the gelatin hydrogel via oxidation cross‐linking. It is reduced by the gallol groups to produce nanogold (AuNP)‐decorated hydrogel (Au‐gel). This Au‐gel is fully characterized by UV–vis, XRD, TEM, SEM, EDX, and ICP‐MS and exhibits a high‐catalytic activity for the reduction of 4‐nitrophenol. The solid Au‐gel catalyst is robust, easily recyclable, and reused at least eight times.     

A Degradable and Antimicrobial Surface‐Attached Polymer Hydrogel

Surface‐attached, degradable polymer hydrogels with potential antimicrobial activity are reported. They are obtained by ring‐opening metathesis copolymerization (ROMP) of a monomer with potential bioactivity and a monomer that carries a benzophenone cross‐linker and a hydrolyzable group. The hydrolyzable group is either an ester or an anhydride group. The copolymers thus obtained are spin‐coated onto silicon wafers and UV‐irradiated to induce C,H cross‐linking of the benzophenone groups and obtain the target polymer networks. Immersion of these networks into aqueous media triggers network degradation. The degradation speed depends on the nature of the intended break points (ester or anhydride groups), the number of cross‐links per polymer chain, and the surrounding medium. By releasing bioactive polymer fragments to the medium (“leaching”) and by regenerating the hydrogel surface during the degradation process, the hydrogels potentially have two ways to prevent biofilm formation on their surface.     

An Injectable ROS‐Responsive Self‐Healing Hydrogel Based on tetra‐poly(ethylene glycol)‐b‐oligo(l‐methionine)

Abnormal physiological conditions provide an ideal stimulus for the design of responsive hydrogels which function as controlled and site‐specific release of drugs. Here, an injectable reactive oxygen species (ROS) responsive self‐healing hydrogel based on tetra‐poly(ethylene glycol)‐b‐oligo (l ‐methionine) (t‐PEG₅₆‐b‐OMeth_n) synthesized by a novel and facile method is reported. The hydrophobic interactions between the side chains of l ‐methionine make the polymer chains crosslinked and lead to the formation of hydrogels which can be injected and self‐healed, meanwhile, the cross‐linker also provides a hydrophobic domain to encapsulate Dox. In presence of ROS, the side chain of l ‐methionine can be oxidized to methionine sulfoxide. The side chain of l ‐methionine is changed accordingly from hydrophobic to hydrophilic. As a result, both the hydrophobic domain and the hydrogel itself are destroyed. The controlled release of Dox by ROS at site‐specific is realized. The excellent biocompatibility of hydrogel based on t‐PEG₅₆‐b‐OMeth_n indicates the door of the potential application in controlled release of drug in a truly physiological environment.     

Covalent Chitosan‐Cellulose Hydrogels via Schiff‐Base Reaction Containing Macromolecular Microgels for pH‐Sensitive Drug Delivery and Wound Dressing

Wound dressings with pH‐sensitive properties, stable mechanical performance, and antibacterial properties have great potential for clinical applications. Herein, drug‐loaded microgels via Schiff‐base reaction between carboxymethyl chitosan and oxidized carboxymethyl cellulose are fabricated. Then they are embedded in hydrogels to form a hydrogel‐microgels composite (Gel/MGs). The gelation time, morphologies, swelling ratio, weight loss ratio, mechanical properties, pH‐sensitive drug release profiles, and antibacterial activities are examined. Adding microgels endows the hydrogels with more stable properties, enhanced mechanical performance, and drug release sensitivity to both acid and alkali in vitro. Gel/MGs dressings show a steady mass after 6 h and even maintain its 95.4% initial mass after 14 days in pH 7.4. In pH 9.5, Gel/MGs dressings also show a higher cumulative release of silver sulfadiazine than that in pH 7.4 and pH 5.5. Gel/MGs/AgSD dressings demonstrate desirable antibacterial properties, which may ensure their potential application in wound dressing.     

A Multitasking Hydrogel Based on Double Dynamic Network with Quadruple‐Stimuli Sensitiveness,Autonomic Self‐Healing Property,and Biomimetic Adhesion Ability

Multifunctional and multiresponsive hydrogels demonstrate excellent promise for multifarious applications but often suffer from high synthesis complexity and poor resource availability. Herein, based on the boronate–catechol interactions between a disulfide‐containing, boronic acid‐based crosslinker, and a catechol‐functionalized poly(N‐isopropyl acrylamide), a multitasking hydrogel with double dynamic network is developed. By integrating the inherent heat‐responsive property of poly(N‐isopropyl acrylamide) and bioadhesion of catechol moieties with the reversibility and dynamic features of boronate ester and disulfide bonds, the final hydrogel is endowed with not only temperature, pH, glucose, and redox quadruple‐stimuli sensitiveness, but also autonomic self‐healing property and biomimetic adhesion ability. Moreover, the rheological and adhesive properties can be readily tuned by adjusting the amount of crosslinker or the catechol in polymer precursor. Considering the readily prepared starting materials, easy preparation, high flexibility in tuning hydrogel properties, the procedure provided here opens up a promising avenue to develop multifunctional hydrogels for multifarious applications.

     

A Non‐ionic Thermophilic Hydrogel with Positive Thermosensitivity in Water and Electrolyte Solution

The first example of a chemically crosslinked synthetic non‐ionic hydrogel showing reversible positive swelling behavior in pure water as well as electrolyte solution is highlighted. Homopolymeric hydrogels are synthesized from N‐acryloylglycinamide with N,N′‐methylenbis(acrylamide) as a chemical crosslinker via free radical polymerization in dimethyl sulfoxide (DMSO). The swelling‐ratio dependency of the hydrogels upon temperature as well as on the amounts of crosslinker from 1 to 4.8 mol% is studied. With 1 mol% crosslinker, the hydrogel is able to take up over three times water of its weight at 37 °C in pure water and phosphate‐buffered saline. All the samples show almost 100% of reversibility for at least 6 d up to 37 °C irrespective of the amount of the crosslinker, making them promising candidates for biomedical applications. The sample with a higher amount of crosslinker, i.e., 4.8 mol% is even stable for over 6 d at 70 °C.

     

Hybrid Hydrogel Networks by Photocrosslinking of Thermoresponsive α,ω‐Itaconyl‐PLGA‐PEG‐PLGA Micelles in Water: Influence of the Lithium Phenyl‐2,4,6‐Trimethylbenzoylphosphinate Photoinitinator

Modification of thermogelling biodegradable copolymers with functional groups enables further covalent crosslinking of physical micelle‐based hydrogels formed at specific temperature in water. The resulting hybrid hydrogel network exhibits an increase in stiffness and degradation stability. In this work, synthesized well‐defined thermoresponsive α,ω‐itaconyl‐poly(d ,l ‐lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactide‐co‐glycolide) (α,ω‐itaconyl‐PLGA‐PEG‐PLGA) macromonomers with a high degree of itaconyl‐substitution providing free double bonds are photocrosslinked in water at both 25 and 37 °C using lithium phenyl‐2,4,6‐trimethylbenzoylphosphinate (LiTPO) acting as water‐soluble non‐toxic photoinitiator. The effect of LiTPO on the thixotropic behavior of macromonomer in water at 25 °C without irradiation is evaluated. With the addition of a low amount of the photoinitiator (0.1 wt%), the degree of copolymer thixotropy increases. However, further increase in the photoinitiator concentration (0.5–3 wt%) leads to a lower degree of thixotropy. The photoinitiator is presumably interfering with the micellar self‐assembly of the copolymer. This trend is also reflected in photocrosslinking efficiency, where the hybrid hydrogel networks with the highest storage moduli are achieved with very low concentrations of the photoinitiator (0.1 wt%) at 25 °C, while this trend is reversed at 37 °C. The hydrolytic stability of hydrogels prepared at 37 °C from 17 wt% macromonomer solution with 1% LiTPO exceeds 22 days.     

Super Stable and Tough Hydrogel Containing Covalent,Crystalline, and Ionic Cross‐Links

A novel hydrogel with super stability and toughness is obtained by polymerizing acrylamide and maleic acid in the presence of poly(vinyl alcohol) chains. Then the hydrogel is processed with dry‐anneal and loading with cation solution method in order to construct a polymer network containing covalent, crystalline, and ionic cross‐links. Various hydrogels are measured via tensile and compressive tests to determine the optimal preparation and mechanical properties of hydrogels. The hydrogels show high tensile stress of ≈ 8 MPa and toughness of ≈ 25.4 MJ m^?3. The hydrogel exhibits good chemical stability that remained up to 93% of original strength after 12 h soaking in phosphate buffered saline. Finally, an energy dissipation mechanism is discussed.

     

Swelling Behaviors of Poly(N‐isopropylacrylamide) Nanosized Hydrogel Particles/Poly(vinyl alcohol)/Water Systems: Effect of the Degree of Hydrolysis of PVA

Using poly(vinyl alcohol) as a drug model, the swelling behaviors of thermosensitive poly(N‐isopropylacrylamide) gel with various concentrations of PVA are investigated. The swelling ratio in PVA9000 is larger than that of PVA89000 at the same composition because the fully hydrolyzed PVA acts as a steric hindrance. A lattice‐based molecular thermodynamic model is used to obtain interaction parameters and then directly applied to describe the swelling behaviors of the gel. Using only one adjustable parameter, the PVA selectivity can be theoretically predicted and the ternary phase diagrams of PNIPA/water/PVA system can be generated. Lastly, the calculated results are compared with the swelling data for PNIPA/PVA copolymer gel, and are found to be in good agreement with the proposed model.

     

Swelling and Mechanical Properties of a Temperature‐Sensitive Dextran Hydrogel and its Bioseparation Applications

Summary: A series of temperature‐sensitive dextran hydrogels (poly(NIPA‐co‐GMA‐Dex)) were synthesized by the copolymerization of glycidyl methacrylate‐derivatized dextran (GMA‐Dex) and N‐isopropylacrylamide (NIPA) in aqueous solution. Their swelling and mechanical properties and bioseparation behaviors were studied. It is found that poly(NIPA‐co‐GMA‐Dex) hydrogels simultaneously exhibit much better swelling and mechanical properties. The interactions between poly(NIPA‐co‐GMA‐Dex) hydrogels and sodium dodecylsulfate (SDS), Rutin, and DL ‐α‐alanine were different because of their different hydrophobic nature, polarity, and molecular structure, and obviously depend on the temperature: the mechanism is discussed. In addition, using poly(NIPA‐co‐GMA‐Dex) hydrogels as the absorbents, gel‐extraction separation experiments of dextran and BSA solutions showed that the separation ability of poly(NIPA‐co‐GMA‐Dex) hydrogels obviously increased upon reaching the LCST.

Temperature dependence of the swelling ratio of the PNIPA (▪) and poly(NIPA‐co‐GMA‐Dex) hydrogels (r = 0.2(•), 0.4 (▴), 0.5 (▾), 0.6(♦), 0.8 (+)).     

Polyvinyl Alcohol‐Based Thermogel with Tunable Gelation and Self‐Healing Property

Injectable thermogelated hydrogels with self‐healing and multi‐responsiveness are emerging as a class of significant “smart” materials because of their many potential applications. However, there are only very limited precedents that combine thermogels with self‐healing and tunable functions. In this work, it is demonstrated that N‐alkyl substituted carbamate modified polyvinyl alcohol with borax as a crosslinker enables a variety of tunable and dynamic thermogelation properties. As far as it is known, this is the first polyvinyl alcohol–based thermogel system. This system characterizes shear thinning, multiple responsiveness, and dynamic gelation features. Systematic investigation suggests that these features collaborate to contribute to attractive injectability, quick self‐healing ability, and tunable thermogelation behavior. A stepwise in situ gelation and carbon dioxide–triggered release are demonstrated.