Physical, chemical, and chemical-physical double network of zwitterionic hydrogels

Zwitterionic hydrogels are very promising for biomedical applications. They are usually copolymerized with other polymers to improve their mechanical properties often at the expense of their biological properties. In this study, physically cross-linked poly(sulfobetaine methacrylate) (polySBMA) hydrogels were prepared, and their physical properties including phase behavior were investigated. Linear polySBMAs, with an average molecular weight ranging from 20.9 kDa to 316 kDa, were prepared via free radical polymerization at different KCl concentrations. The opaque-transparent phase transition of polySBMA-water mixtures were measured using a UV-vis spectrometer. Analysis from dynamic rheometry showed the formation of physically cross-linked hydrogels with mechanical ductility due to reversible charge interactions. Chemically cross-linked hydrogels were also prepared, and their swelling and mechanical properties were evaluated. It was found that the introduction of cross-linkers could lead to a decrease in the amount of physical cross-links in chemical hydrogels. In order to improve the mechanical properties of SBMA hydrogels, linear polySBMA was introduced to the network of chemically cross-linked polySBMA gels, creating a chemical-physical double network (DN) with both chemical and physical cross-links. The chemical-physical DN provides a desirable method to improve the mechanical properties of zwitterionic hydrogels without introducing other hydrophobic moieties.     

Fracture Behavior of Two Highly Stretchable Double Network Hydrogels

The static and dynamic mechanical behavior of two double network (DN) hydrogels, alginate/polyacrylamide (PAAm) hybrid hydrogel and sodium poly(2-acrylamido-2-methylpropanesulfonic acid) PNaAMPS/PAAm, is presented to understand the role played by different cross-linked networks on fracture and recovery properties. Although with a smaller modulus, alginate/PAAm hybrid hydrogel had a much higher stretchability, whether with or without notches, in the tensile tests. Continuous step strain measurement by using a strain-controlled parallel-plate rheometer showed that alginate/PAAm can immediately recover its mechanical properties after breakdown, while PNaAMPS/PAAm didn't show mechanical recovery at all.     

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.     

DNA-based supramolecular hydrogels: From construction strategies to biomedical applications

DNA-based supramolecular hydrogels are important and promising biomaterials for various applications due to their inherent biocompatibility and tunable physicochemical properties. The three-dimensional supramolecular matrix of DNA formed by non-covalently dynamic cross-linking provides exceptional adaptability, self-healing, injectable and responsive properties for hydrogels. In addition, DNA hydrogels are also ideal bio-scaffold materials owing to their tissue-like mechanics and intrinsic biological functions. Technically, DNA can assemble into supramolecular networks by pure complementary base pairing; it can also be combined with other building blocks to construct hybrid hydrogels. This review focuses on the development and construction strategies of DNA hydrogels. Assembly and synthesis methods, diverse responsiveness and biomedical applications are summarized. Finally, the challenges and prospects of DNA-based supramolecular hydrogels are discussed.     

A facile way to tune mechanical properties of artificial elastomeric proteins-based hydrogels

Protein-based hydrogels have attracted considerable interests due to their potential applications in biomedical engineering and material sciences. Using a tandem modular protein (GB1)(8) as building blocks, we have engineered chemically cross-linked hydrogels via a photochemical cross-linking strategy, which is based on the cross-linking of two adjacent tyrosine residues into dityrosine adducts. However, because of the relatively low reactivity of tyrosine residues in GB1, (GB1)(8)-based hydrogels exhibit poor mechanical properties. Here, we report a Bolton-Hunter reagent-based, facile method to improve and tune the mechanical properties of such protein-based hydrogels. Using Bolton-Hunter reagent, we can derivatize lysine residues with phenolic functional groups to modulate the phenolic (tyrosine-like) content of (GB1)(8). We show that hydrogels made from derivatized (GB1)(8) with increased phenolic content show significantly improved mechanical properties, including improved Young's modulus, breaking modulus as well as reduced swelling. These results demonstrate the great potential of this derivatization method in constructing protein-based biomaterials with desired macroscopic mechanical properties.     

Hybrid hydrogels based on cross-linked polyacrylic acid and polyvinyl alcohol as electrically controlled artificial muscles

A procedure was developed for preparing hybrid hydrogel specimens of preset configuration from cross-linked polyacrylic acid and polyvinyl alcohol. The specimens exhibit higher mechanical characteristics compared to hydrogels of cross-linked polyacrylic acid. Hydrogel specimens fabricated in the form of elastic rings demonstrate an electromechanical response, contraction on passing electric current through their cross section. This effect is more pronounced for the specimens swollen in a sodium sulfate solution than for those swollen in distilled water. The results obtained show that the hydrogels can be used as a linearly operating mechanical force generator (artificial muscle).     

Viscoelastic and fractal characteristics of a supramolecular hydrogel hybridized with clay nanoparticles

The supramolecular hydrogels derived from low-molecular-mass gelators represent a unique class of soft matters and have important potential applications in biomedical fields, separation technology and cosmetic science. However, they suffer usually from weak mechanical and viscoelastic properties. In this work, we carry out the in situ hybridization of clay nanoparticles (Laponite RD) into the supramolecular hydrogel formed from a low-molecular-mass hydrogelator, 2,6-di[N-(carboxyethyl carbonyl)amino]pyridine (DAP), and investigate the viscoelastic and structural characteristics of resultant hybrid hydrogel. It was found that a small concentration of Laponite RD could lead to a significant increase in the storage modulus, loss modulus or complex viscosity. Compared with neat DAP hydrogel, the hybrid hydrogel has a greater hydrogel strength and a lower relaxation exponent. In particular, the enhancement of the clay nanoparticles to the viscoelastic properties of the DAP hydrogel is more effective in the case of higher DAP concentration. By relating its macroscopic elastic properties to a scaling fractal model, such a hybrid hydrogel was confirmed to be in the strong-link regime and to have a more complex network structure with a higher fractal dimension when compared with neat DAP hydrogel.     

Dual cross-linked networks hydrogels with unique swelling behavior and high mechanical strength: based on silica nanoparticle and hydrophobic association

A series of physically cross-linked hydrogels composed poly(acrylic acid) and octylphenol polyoxyethylene acrylate with high mechanical strength are reported here with dual cross-linked networks that formed by silica nanoparticles (SNs) and hydrophobic association micro-domains (HAMDs). Acrylic acid (AA) and octylphenol polyoxyethylene acrylate with 10 ethoxyl units (OP-10-AC) as basic monomers in situ graft from the SNs surface to build poly(acrylic acid) hydrophilic backbone chains with randomly distributed OP-10-AC hydrophobic side chains. The entanglements among grafted backbone polymer chains and hydrophobic branch architecture lead to the SNs and HAMDs play the role of physical cross-links for the hydrogels network structure. The rheological behavior and polymer concentration for gelation process are measured to examine the critical gelation conditions. The correlation of the polymer dual cross-linked networks with hydrogels swelling behavior, gel-to-sol phase transition, and mechanical strength are addressed, and the results imply that the unique dual cross-linking networks contribute the hydrogels distinctive swelling behavior and excellent tensile strength. The effects of SNs content, molecular weight of polymer backbone, and temperature on hydrogels properties are studied, and the results indicate that the physical hydrogel network integrity is depended on the SNs and HAMDs concentration.     

Injectable supramolecular hybrid hydrogels formed by MWNT‐grafted‐poly(ethylene glycol) and α‐cyclodextrin

Poly(ethylene glycol)‐grafted‐multiwalled carbon nanotube (MWNT‐g‐PEG) was synthesized by a coupling reaction and formed inclusion complexes (ICs) after selective threading of the PEG segment of the MWNT‐g‐PEG through the cavities of α‐cyclodextrins (α‐CDs) units. The polypseudorotaxane structures of the as‐obtained hydrogels were confirmed by ¹H NMR, X‐ray diffraction and DSC analyses. The complexation of the PEG segments with α‐CDs and the hydrophobic interaction between the MWNT resulted in the formation of supramolecular hybrid hydrogels with a strong network. Thermal analysis showed that the thermal stability of the hydrogel was substantially improved by up to 100 °C higher than that of native hydrogel. The resultant hybrid hydrogels were found to be thixotropic and reversible, and could be applied as a promising injectable drug delivery system. The mechanical strength of the hybrid hydrogels was greatly improved in comparison with that of the corresponding native hydrogels. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3145–3151, 2010     

Multi-bond network hydrogels with robust mechanical and self-healable properties

Multi-bond network(MBN) which contains a single network with hierarchical cross-links is a suggested way to fabricate robust hydrogels. In order to reveal the roles of different cross-links with hierarchical bond energy in the MBN, here we fabricate poly(acrylic acid) physical hydrogels with dual bond network composed of ionic cross-links between carboxylFe3+ interactions and hydrogen bonds, and compare these dually cross-linked hydrogels with singly and ternarily cross-linked hydrogels. Simple models are employed to predict the tensile property, and the results confirm that the multi-bond network with hierarchical distribution in the bond energy of cross-links endows hydrogel with effective energy-dissipating mechanism. Moreover, the dually cross-linked MBN gels exhibit excellent mechanical properties(tensile strength up to 500 k Pa, elongation at break ~ 2400%) and complete self-healing after being kept at 50 °C for 48 h. The factors on promoting self-healing are deeply explored and the dynamic multi-bonds are regarded to trigger the self-healing along with the mutual diffusion of long polymer chains and ferric ions.     

Fibrous crystalline hydrogels formed from polymers possessing a linear poly(ethyleneimine) backbone

Novel thermoreversible physical hydrogels formed from polymers with linear and star architectures possessing a linear poly(ethyleneimine) (PEI) backbone have been investigated. The hydrogelation occurred simply upon natural cooling of hot aqueous solutions of PEIs to room temperature. The X-ray diffraction and differential scanning calorimetry measurements for the resultant hydrogels unambiguously indicated that the hydrogelation originated from the formation of dihydrate crystalline structures of PEI. These crystalline hydrogels are structurally unique and hierarchical. Microscopic images revealed that the morphologies of the crystalline hydrogels depend on their molecular architectures. The linear PEI resulted in branched fibrous bundles organized by unit crystalline nanofibers with a width of ca. 5-7 nm. The six-armed star with benzene ring core produced fanlike fibrous bundles while the four-armed star with porphyrin core assembled into asterlike aggregates. The critical concentration of gelation (C(G)) was low (about 0.2 approximately 0.3%) and the thermoreversible gel-sol transition temperatures (T(G)) were controllable from approximately 43 to approximately 79 degrees C. The hydrogels formed in the presence of the various aqueous additives including organic solvents, hydrophilic polymers, physical cross-linker, chemical cross-linker, and base enabling modification and functionalization during synthesis. The mechanical properties of the hydrogels could be improved by chemical cross-linking of preformed hydrogels by glutaraldehyde. Physically and physical/chemical cross-linked hydrogels served as excellent template roles in biomimetic silicification, which produced silica-PEI hybrid powder or monolith constructed by nanofibers.     

Gelator-polysaccharide hybrid hydrogel for selective and controllable dye release

In this paper, 1,4-bi(phenylalanine-diglycol)-benzene (PDB) based Low-Molecular-Weight-Gelator (LMWG) hydrogels are modified using hydrophilic polysaccharide (sodium alginate). A set of techniques including Fourier transform infrared (FT-IR) spectroscopy, ¹H Nuclear Magnetic Resonance (¹H NMR), X-ray powder diffraction (XRD), Ultraviolet-Visible (UV-Vis), and circular dichroism (CD) had confirmed a β-turn arrangement of PDB gelators and a semi-interpenetrating network (semi-IPN), which was formed through hydrogen bonds between LMWG fibers and polysaccharide chains. The evaluation of physicochemical properties of hydrogels indicates that gelator-polysaccharide hybrid hydrogels possess better mechanical and water retention properties than LMWG hydrogels. The release study of dyes (model drug) from both LMWG and hybrid hydrogels was carried out. Compared with PDB based hydrogels, hybrid hydrogels show a selective and controllable release property for certain dyes. The results suggest LMWG-polysaccharide hybrid gels may find potential applications as promising drug delivery vehicles for drug molecules.     

Preparation and characterization of a novel stimuli-responsive nanocomposite hydrogel with improved mechanical properties

A novel stimuli-responsive organic/inorganic nanocomposite hydrogel (NC hydrogel) with excellent mechanical properties was synthesized by in situ polymerization of 2-(2-methoxyethoxy) ethyl methacrylate (MEO(2)MA), oligo (ethylene glycol) methacrylate (OEGMA) and acrylic acid (AAc), as the polymeric matrix (PMOA), and fibrillar attpulgite (AT), as the reinforcer and cross-linker. The effect of the AT content on the mechanical properties for the swollen and dried NC hydrogels was determined by tensile testing and dynamic mechanical analysis (DMA), respectively. The tensile testing results showed that the incorporation of AT nanoparticles significantly enhanced the mechanical properties of NC hydrogels. As the content of AT increased, the tensile strength, tensile modulus and effective cross-linked chain density increased. The DMA results showed that the storage modulus of AT/PMOA NC hydrogels was increased and the glass transition temperatures shifted to higher temperature compared to the pure PMOA hydrogel, which further indicated that the enhancement of mechanical property depended upon the presence and content of AT. In addition, the faster swelling rates of the NC hydrogels were observed in comparison with the corresponding physically cross-linked PMOA hydrogel, except for 1% AT/PMOA sample. However, the deswelling kinetics of NC hydrogels was obviously retarded.     

A new polymer/clay nano-composite hydrogel with improved response rate and tensile mechanical properties

A new type of stimuli-responsive organic/inorganic nano-composite hydrogel was prepared by introducing fibrillar attapulgite into poly(2-hydroxyethyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate-co-methacrylic acid) network, in which the nanosized attapulgite fibril worked as the cross-linker instead of conventional chemical cross-linker. In the preparation process, a prepolymerization route was adopted to effectively stabilize the dispersion of attapulgite. The structure and morphology of the nano-composite hydrogels were characterized by SEM, FTIR and DSC. The swelling/deswelling behaviors and tensile mechanical properties of the nano-composite hydrogels were compared with that of the corresponding chemically cross-linked hydrogel. The results showed that the nano-composite hydrogels had much greater equilibrium-swelling ratio, much faster response rate to pH and significantly improved tensile mechanical properties. As the content of AT increased, the tensile strength, effective cross-link chain density and glass transition temperature increased, while the equilibrium swelling ratio, deswelling rate and elongation at break decreased.     

强韧型自愈合水凝胶的研究进展

水凝胶作为一种由大量水和与众不同的三维网状结构构成的智能软材料,已经广泛应用于许多领域,如药物输送、软骨修复、废物处理及电子设备等。然而,水凝胶不良的机械性能及自愈合性极大地限制了它们的潜在应用。目前已报道的韧性水凝胶通常不具有或只有很弱的自修复性,而自修复水凝胶通常机械性能非常弱。因此,研发具有高效自修复性能和优异机械性能的水凝胶材料,无论是从学术角度还是工业角度都是非常重要的。本文总结了近些年来强韧型自愈合水凝胶的最新研究进展,从其制备方法、性能等方面进行了简要介绍,并对未来的发展前景进行了展望。     

Stimulus-responsive hydrogels made from biosynthetic fibrinogen conjugates for tissue engineering: structural characterization

Nanostructured hydrogels based on "smart" polymer conjugates of poloxamers and protein molecules were developed in order to form stimulus-responsive materials with bioactive properties for 3-D cell culture. Functionalized Pluronic F127 was covalently attached to a fibrinopeptide backbone and cross-linked into a structurally versatile and mechanically stable polymer network endowed with bioactivity and temperature-responsive structural features. Small angle X-ray scattering and transmission electron microscopy combined with rheology were used to characterize the structural and mechanical features of this biosynthetic conjugate, both in solution and in hydrogel form. The temperature at which the chemical cross-linking of F127-fibrinopeptide conjugates was initiated had a profound influence on the mechanical properties of the thermo-responsive hydrogel. The analysis of the scattering data revealed modification in the structure of the protein backbone resulting from increases in ambient temperature, whereas the structure of the polymer was not affected by ambient temperature. The hydrogel cross-linking temperature also had a major influence on the modulus of the hydrogel, which was rationally correlated to the molecular structure of the polymer network. The hydrogel structure exhibited a small mesh size when cross-linked at low temperatures and a larger mesh size when cross-linked at higher temperatures. The mesh size was nicely correlated to the mechanical properties of the hydrogels at the respective cross-linking temperatures. The schematic charts that model this material's behavior help to illustrate the relationship that exists between the molecular structure, the cross-linking temperature, and the temperature-responsive features for this class of protein-polymer conjugates. The precise control over structural and mechanical properties that can be achieved with this bioactive hydrogel material is essential in designing a tissue-engineering scaffold for clinical applications.     

Self-assembly in magnetic supramolecular hydrogels

Most recent advances in the synthesis of supramolecular hydrogels based on low molecular weight gelators (LMWGs) have focused on the development of novel hybrid hydrogels, combining LMWGs and different additives. The dynamic nature of the noncovalent interactions of supramolecular hydrogels, together with the specific properties of the additives included in the formulation, allow these novel hybrid hydrogels to present interesting features, such as stimuli-responsiveness, gel-sol reversibility, self-healing and thixotropy, which make them very appealing for multiple biomedical and biotechnological applications. In particular, the inclusion of magnetic nanoparticles in the hydrogel matrix results in magnetic hydrogels, a particular type of stimuli-responsive materials that respond to applied magnetic fields. This review focuses on the recent advances in the development of magnetic supramolecular hydrogels, with special emphasis in the role of the magnetic nanoparticles in the self-assembly process, as well as in the exciting applications of these materials.     

Stimuli-responsive nanocomposite gels

A new class of polymer hydrogels, nanocomposite hydrogels (NC gels), consisting of a unique organic (polymer)/inorganic (clay) network structure, was synthesized by in situ free-radical polymerization in the presence of exfoliated clay nanoparticles in an aqueous system. The resulting NC gels overcame most of the disadvantages associated with chemically cross-linked hydrogels, such as mechanical fragility, structural heterogeneity, and slow de-swelling rate. By using thermo-sensitive poly(N-isopropylacrylamide) (PNIPA) as a constituent polymer, NC gels with remarkable mechanical, optical, and swelling properties as well as thermo-sensitivity were obtained. The various properties of NC gels, such as transparency, gel volume, cell culturing, and surface friction changed significantly in response to the temperature and surrounding conditions. All the excellent properties and new stimuli-responsive characteristics of NC gels are attributed to the unique PNIPA/clay network structure. The thermo-sensitivities and the transition temperature can largely be controlled by varying the clay content and by the addition of solutes.     

Evaluation of the degree of cross-linking of cellulose-based superabsorbent hydrogels: a comparison between different techniques

Three different techniques have been applied to the evaluation of the degree of cross-linking of superabsorbent cellulose-based hydrogels obtained from water solutions of carboxymethylcellulose sodium salt (CMCNa) and hydroxyethylcellulose (HEC), chemically cross-linked with divinyl sulfone. These polyelectrolyte hydrogels are biodegradable and have the same sorption capacity as acrylate-based superabsorbents on the market. A ¹³C solid state NMR analysis was carried out on dry samples of hydrogel to obtain the degree of cross-linking, an important parameter that affects the swelling and mechanical properties of a hydrogel. Dynamic mechanical analysis was performed during the hydrogel cross-linking using a parallel plate rheometer under oscillatory deformations in order to monitor the evolution of the hydrogel viscoelastic properties during the synthesis. The value of |G*| and the slope of the stress-deformation ratio plots from uniaxial compression tests were used to evaluate the elastically effective degree of cross-linking according to classical rubber elasticity theory. Moreover, a dynamic mechanical analysis was carried out on cross-linked hydrogels at different degrees of swelling in order to investigate the influence of the swelling on the mechanical properties and the application of rubber elasticity theory to swollen hydrogels.     

Hierarchically structured free-standing hydrogels with liquid crystalline domains and magnetic nanoparticles as dual physical cross-linkers

Here we report a modular strategy for preparing physically cross-linked and mechanically robust free-standing hydrogels comprising unique thermotropic liquid crystalline (LC) domains and magnetic nanoparticles both of which serve as the physical cross-linkers resulting in hydrogels that can be used as magnetically responsive soft actuators. A series of amphiphilic LC pentablock copolymers of poly(acrylic acid) (PAA), poly(5-cholesteryloxypentyl methacrylate) (PC5MA), and poly(ethylene oxide) (PEO) blocks in the sequence of PAA-PC5MA-PEO-PC5MA-PAA were prepared using reversible addition-fragmentation chain transfer polymerization. These pentablock copolymers served as macromolecular ligands to template Fe(3)O(4) magnetic nanoparticles (MNPs), which were directly anchored to the polymer chains through the coordination bonds with the carboxyl groups of PAA blocks. The resulting polymer/MNP nanocomposites comprised a complicated hierarchical structure in which polymer-coated MNP clusters were dispersed in a microsegregated pentablock copolymer matrix that further contained LC ordering. Upon swelling, the hierarchical structure was disrupted and converted to a network structure, in which MNP clusters were anchored to the polymer chains and LC domains stayed intact to connect solvated PEO and PAA blocks, leading to a free-standing LC magnetic hydrogel (LC ferrogel). By varying the PAA weight fraction (f(AA)) in the pentablock copolymers, the swelling degrees (Q) of the resulting LC ferrogels were tailored. Rheological experiments showed that these physically cross-linked free-standing LC ferrogels exhibit good mechanical strength with storage moduli G' of around 10(4)-10(5) Pa, similar to that of natural tissues. Furthermore, application of a magnetic field induced bending actuation of the LC ferrogels. Therefore, these physically cross-linked and mechanically robust LC ferrogels can be used as soft actuators and artificial muscles. Moreover, this design strategy is a versatile platform for incorporation of different types of nanoparticles (metallic, inorganic, biological, etc.) into multifunctional amphiphilic block copolymers, resulting in unique free-standing hybrid hydrogels of good mechanical strength and integrity with tailored properties and end applications.