A Double Network Hydrogel with High Mechanical Strength and Shape Memory Properties

Double network (DN) hydrogels as one kind of tough gels have attracted extensive attention for their potential applications in biomedical and load-bearing fields. Herein, we import more functions like shape memory into the conventional tough DN hydrogel system. We synthesize the PEG-PDAC/P(AAm-co-AAc) DN hydrogels, of which the first network is a well-defined PEG (polyethylene glycol) network loaded with PDAC (poly(acryloyloxyethyltrimethyl ammonium chloride)) strands, while the second network is formed by copolymerizing AAm (acrylamide) with AAc (acrylic acid) and cross-linker MBAA (N, N'-methylenebisacrylamide). The PEG-PDAC/P(AAm-co-AAc) DN gels exhibits high mechanical strength. The fracture stress and toughness of the DN gels reach up to 0.9 MPa and 3.8 MJ/m³, respectively. Compared with the conventional double network hydrogels with neutral polymers as the soft and ductile second network, the PEG-PDAC/P(AAm-coAAc) DN hydrogels use P(AAm-co-AAc), a weak polyelectrolyte, as the second network. The AAc units serve as the coordination points with Fe³⁺ ions and physically crosslink the second network, which realizes the shape memory property activated by the reducing ability of ascorbic acid. Our results indicate that the high mechanical strength and shape memory properties, probably the two most important characters related to the potential application of the hydrogels, can be introduced simultaneously into the DN hydrogels if the functional monomer has been integrated into the network of DN hydrogels smartly.     

Effect of polymer entanglement on the toughening of double network hydrogels

The mechanical strength of double network (DN) gels consisting of highly cross-linked poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) as the first component and linear polyacrylamide (PAAm) as the second component has been investigated by varying the molecular weight of the second polymer PAAm, M(w). The experimental results reveal that, for toughening of the DN gels, (1) M(w) is one of the dominant parameters; (2) there is a critical value of M(w) = 10(6) for a remarkable enhancement; (3) the fracture energy of DN gels with a M(w) larger than 10(6) reaches a value as high as 10(3) J/m(2). By plotting the strength of DN gels (fracture stress sigma and fracture energy G) against a characteristic parameter of c[eta], where c is the average concentration of PAAm in the DN gels and [eta] is the intrinsic viscosity of PAAm, it is found that the dramatic increase in the mechanical strength of the DN gels occurs above the region where linear PAAm chains are entangled with each other. Thus, we conclude that the entanglement between the second component PAAm plays an important role of the toughening mechanism of DN gels. This result supports the heterogeneous model, which predicts the presence of "voids" of the first network PAMPS with a size much larger than the radius of the second polymer PAAm.     

Determination of fracture energy of high strength double network hydrogels

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.     

Double network hydrogels with controlled shape deformation: A mini review

Double network hydrogels (DN gels), consisting of two networks with strongly asymmetric network structures and properties, are one of most investigated high strength hydrogels. In most cases, the first network of DN gels is rigid, brittle and tightly crosslinked, while the second network is soft, ductile and loosely crosslinked. Because of the tunable and diverse network structures, DN gels with controlled shape deformation have attracted great attention in recent years. The shape deformation of DN gels can be controlled by first network, second network, or both networks. In this mini review, the shape deformation of DN gels via different networks will be summarized, and the application and future perspectives also are discussed. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1351–1362     

Effect of void structure on the toughness of double network hydrogels

Introduction of soft filler in a hard body, which is one of the common toughening methods of hard polymeric materials, was applied for further toughening of robust double network (DN) hydrogels composed of poly(2‐acrylamido‐2‐methylpropanesulfonic acid) gels (PAMPS gels) as the first component and polyacrylamide (PAAm) as the second component. The fracture energy of the DN gels with the void structure (called void‐DN gels) became twice when the volume fraction of void was 1–3 vol % and the void diameter was much larger than the Flory radius of the PAAm chains. Such toughening was induced by wider range of internal fracture of the PAMPS network derived from partial stress concentration near void structure. Considering the mechanical tests and the dynamic light scattering results, it is implied that the absence of the load‐bearing PAAm structure inside the void is important for the toughening. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1246–1254, 2011     

Rhodamine Mechanophore Functionalized Mechanochromic Double Network Hydrogels with High Sensitivity to Stress

Mechanochromic hydrogels, a new class of stimuli-responsive soft materials, have potential applications in a number of fields such as damage reporting and stress/strain sensing. We prepared a novel mechanochromic hydrogel using a strategy that has been developed to prepare dual-network(DN) hydrogels. A hydrophobic rhodamine derivative(Rh mechanophore) was covalently incorporated into a first network as a cross-linker. This first network embedded with Rh mechanophore within the DN hydrogel was pre-stretched. This guaranteed that the stress could be transferred extensively to the Rh-crosslinked first network once the hydrogel was under an applied force. Interestingly, we found that the threshold stress required to activate the mechanochromism of the hydrogel was less than 200 kPa, and much less than those in previous reports. Moreover, because of the excellent sensitivity of the hydrogel to stress, the DN hydrogel exhibited reversible freezing-induced mechanochromism. Benefiting from the sensitivity of Rh mechanophore to both p H and force, the DN hydrogel showed p H-regulated mechanochromic behavior. Our experimental results indicate that the preparation strategy we used introduces sensitive mechanochromism into the hydrogel and preserves the advantageous mechanical properties of the DN hydrogel. These results will be beneficial to the design and preparation of mechanochromic hydrogels with high stress sensitivity, and foster their practical applications in a number of fields such as damage reporting and stress/strain sensing.     

Electro‐conductive double‐network hydrogels

Novel electro‐conductive and mechanically‐tough double network polymer hydrogels (E‐DN gels) were synthesized by polymerization of 3, 4‐ethylenedioxythiophene in the presence of a double network hydrogel (DN gel) matrix. The E‐DN gels showed not only excellent mechanical performance, having a fracture stress of 1.4–2.1 MPa, but also electrical conductivity as high as 10^?3 S cm^?1, both under dry and water‐swollen states. The fracture stress and fracture energy of the E‐DN gel was increased by 1.7 and 3.4 times, respectively, as compared with the DN gel. From scanning electron microscope and AFM observations, it was found that electro‐conductive poly(3,4‐ethylenedioxythiophene) (PEDOT) was incorporated into DN gel matrix, apparently due to the formation of a poly‐ion complex with sulfonic acid group of the DN gel network. Thus, PEDOT incorporated into the DN gel matrix greatly improves not only electronic conductivity, but also mechanical properties, reinforcing the double network gel matrix. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

SUPER TOUGH GELS WITH A DOUBLE NETWORK STRUCTURE

Living tissues work with fantastic functions in soft and wet gel-like state.Thus,hydrogels have attracted much attention as excellent soft and wet materials,suitable tot making artificial organs for medical treatments.However, conventional hydrogels are mechanically too weak for practical uses.We have created double network (DN) hydrogels with extremely high mechanical strength in order to overcome this problem.DN gels are interpenetrating network (IPN) hydrogels consisting of rigid polyelectrolyte and s...     

Ligament-like tough double-network hydrogel based on bacterial cellulose

Using the double-network (DN) method, bacterial cellulose/polyacrylamide (BC/PAAm) DN gels able to sustain not only high elongation but also high compression have been synthesized by combining BC gel as the first network with PAAm as the second network in the presence of N,N′-methylene bisacrylamide (MBAA) as a cross-linker. This DN gel was obtained by modifying the monomer concentration of the second network, acrylamide monomer (AAm) and MBAA, and by controlling the water content of the first network, BC gel. The mechanical properties are discussed in term of the swelling degree (q), which is independent of the concentration of AAm and MBAA. It was found that, for BC/PAAm DN gels with the first network formed from BC gel with high q (BC _q=120), the tensile and compressive modulus (E) scales with q as E μ q ^{- 2} E \propto q^{ - 2} . The tensile fracture stress, σ _F, of this DN gel was almost independent of q, that is s_\textF μ q⁰, \sigma_{\text{F}} \propto q^{0}, but the compressive fracture stress, σ _F, scaled with q as E μ q ^{- 2} E \propto q^{ - 2} . Meanwhile, the tensile and compressive fracture strain (ε _F) of the gel is almost independent of q, which is caused by AAm concentration change, but linearly increased with q, which is caused by MBAA concentration change. Furthermore, by decreasing the water content of the BC gel prior to polymerization of the second (PAAm) network, a ligament-like tough BC/PAAm DN gel could be obtained with tensile strength of 40 MPa.     

SUPER TOUGH GELS WITH A DOUBLE NETWORK STRUCTURE

 Living tissues work with fantastic functions in soft and wet gel-like state. Thus, hydrogels have attracted much attention as excellent soft & wet materials, suitable for making artificial organs for medical treatments.However, conventional hydrogels are mechanically too weak for practical uses. We have created double network (DN) hydrogels with extremely high mechanical strength in order to overcome this problem. DN gels are interpenetrating network (IPN) hydrogels consisting of rigid polyelectrolyte and soft neutral polymer. Their excellent mechanical properties cannot be explained by the standard fracture theories. In this paper, we discuss about the toughening mechanism of DN gels in accordance with their characteristic behavior, such as large hysteresis and necking phenomenon. We also describe the results on tissue engineering application of DN gels.     

PVA改性PAMPS-PAM超高力学性能双网络水凝胶的制备

采用紫外光引发聚合制备了聚乙烯醇(PVA)改性的聚(2-丙烯酰胺基-2-甲基丙磺酸)-聚丙烯酰胺(PAMPS-PAM)双网络(DN)水凝胶.测定并比较了PVA改性前后PAMPS-PAM双网络水凝胶的溶胀动力学;通过扫描电子显微镜(SEM)观察了单网络水凝胶的结构;测定PVA改性前后PAMPS-PAM双网络水凝胶的压缩及拉伸性能.结果表明,经PVA改性后的PAMPS-PAM双网络水凝胶有较高的溶胀比;0.82%PVA用量的PAMPS-PAM双网络水凝胶在90%压缩形变率下仍保持完整、最大拉伸应力达到0.5 MPa,大幅提高PAMPS-PAM双网络水凝胶的力学性能.     

聚乙二醇对PAMPS/PAM双网络水凝胶性能的影响

采用紫外光引发聚合制备了聚乙二醇(PEG)改性的聚(2-丙烯酰胺-2-甲基丙磺酸)/聚丙烯酰胺(PAMPS/PAM)双网络水凝胶.测定并比较了PEG改性前后双网络水凝胶的溶胀动力学以及单网络水凝胶中丙烯酰胺(AM)的吸收量;用扫描电子显微镜(SEM)观察了单网络水凝胶的结构;测定PEG改性前后双网络水凝胶的压缩及拉伸性能.结果表明,经PEG改性后的双网络水凝胶有较高的溶胀比;改性后单网络水凝胶更易吸收AM;改性后双网络水凝胶压缩形变率达到90%以上、拉伸形变率是未改性双网络水凝胶的2倍.     

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.     

Synthesis of organic‐inorganic hybrid gels by means of thiol‐ene and azide‐alkene reactions

Organic–inorganic hybrid gels have been synthesized from a multi‐vinyl functional cyclic siloxane, 1,3,5,7‐tetravinyltetramethylcyclotetrasiloxane (TVMCTS), or a cubic silsesquioxane, octavinyloctasilasesquioxane (PVOSS), and α,ω‐dithiol compounds, 1,6‐hexanedithiol (HDT), 1,10‐decanedithiol (DDT), using thiol‐ene reaction in toluene. The network structure of the resulting gels, mesh size and mesh size distribution, was quantitatively characterized by means of a scanning microscopic light scattering (SMILS). The gels obtained from TVMCTS‐HDT formed homogeneous network structure with 1.5–1.6 nm mesh. Relaxation peaks derived from large clusters and/or micro gels were detected in the SMILS analysis of the TVMCTS‐DDT, PVOSS‐HDT, and PVOSS‐DDT gels besides those from the small meshes. The organic–inorganic hybrid gels were also synthesized from TVMCTS, PVOSS with α,ω‐diazide compounds, 1,6‐hexanediazide (HDA), 1,10‐decanediazide (DDA), using azide‐alkene reaction in toluene. All the gels obtained with the azide‐alkene reaction formed the homogeneous network structure. Enthalpy relaxation at the glass transition of the dried samples was detected by differential scanning calorimetry to study the network uniformity of the original gels. The gels synthesized by the azide‐alkene reaction showed larger enthalpy than the gels synthesized by the thiol‐ene reaction, indicating homogeneous network structure in the former gels. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2229–2238     

Biomimetic double network hydrogels: Combining dynamic and static crosslinks to enable biofabrication and control cell-matrix interactions

Hydrogels are promising candidates for recapitulation of the native extracellular matrix (ECM), yet recreating molecular and spatiotemporal complexity within a single network remains a challenge. Double network (DN) hydrogels are a promising step towards recapitulating the multicomponent ECM and have enhanced mechanical properties. Here, we investigate DNs based on dynamic covalent and covalent bonds to mimic the dynamicity of the ECM and enable biofabrication. We also investigate the spatiotemporal molecular attachment of a bioactive adhesive peptide within the networks. Using oxidized alginate (dynamic network, Schiff base) and polyethylene glycol diacrylate (static network, acrylate polymerization) we find an optimized procedure, where the dynamic network is formed first, followed by the static network. This initial dynamically cross-linked hydrogel imparts self-healing, injectability, and 3D printability, while the subsequent DN hydrogel improves the stability of the 3D gels and imparts toughness. Rheology and compression testing show that the toughening is due to the combination of energy dissipation (dynamic network) and elasticity (static network). Furthermore, where we place adhesive sites in the network matters; we find distinct differences when an adhesive peptide, Arg-Gly-Asp (RGD), is attached to the different networks. This DN strategy bring us closer to understanding and recreating the complex multicomponent ECM—pushing us past a materials view of cell adhesion—while enabling injectabiltiy and printing of tough hydrogels.     

Microgel,nanogel and hydrogel–hydrogel semi-IPN composites for biomedical applications: synthesis and characterization

Quaternary ammonium salt hydrogels from a cationic monomer, (3-acrylamidopropyl)-trimethylammonium chloride (APTMACl), in a variety sizes such as bulk, micro- and nano- has been prepared. The synthesis of micro- and nanogels were carried out in the microenvironment of water-in-oil microemulsions using two types of surfactants, namely, L-α- phosphatidylcholine (lecithin) and dioctyl sulfosuccinate sodium salt (AOT). Additionally, hydrogel–hydrogel composite semi-interpenetrating polymer networks (semi-IPN) was synthesized by dispersing previously prepared micro/nanogel into neutral monomers such as acrylamide (AAm) or 2-hydroxylethyl methcarylate (HEMA) before network formation. Hydrogel swelling and pH response behaviors have been investigated for bulk gels. Morphology, structure, and size of nano-, micro- and bulk materials were explored utilizing transmission electron microcopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was confirmed with gel electrophoresis that completely charged nanogel form a strong complex with DNA.     

A pH‐sensitive,strong double‐network hydrogel: Poly(ethylene glycol) methyl ether methacrylates–poly(acrylic acid)

We here describe new double network (DN) hydrogels with excellent mechanical strength and high sensitivity to pH changes. The first polymer network has a bottle brush structure and is formed from oligo‐monomers of poly(ethylene glycol) methyl ether methacrylate (PEGMA). Poly(acrylic acid) (PAA) is used as the second network. This double network features strong intermolecular interactions between the neutral poly(ethylene glycol) (PEG) side chains of PPEGMA and the non‐ionized carboxylic acid groups of the PAA second network. When immersed in solutions with a pH below ～4 the DN hydrogels have a low swelling ratio and are opaque as a result of solvent‐polymer phase separation driven by the formation of dense hydrogen‐bonded clusters. The compression strength (～8 MPa) is at least 14 times higher than the analogous single networks. When immersed in solutions with a pH >4, the hydrogels are transparent and exhibit a high swelling ratio with a compression strength of ～1 MPa. The PEG side chain length can be readily controlled without greatly altering the overall DN topology by choosing PEGMA monomers having different PEG side chain lengths. Longer PEG side branches give higher compression and tensile strengths at pH <4 when hydrogen bonded clusters form. The robust nature of these DN gels over a wide pH range may be useful for applications such as artificial muscles and controlled release devices. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

结冷胶与聚乙二醇丙烯酸酯双网络凝胶的制备及生物相容性评价

针对结冷胶脆性较大的问题,将聚乙二醇丙烯酸酯(PEGDA)引入结冷胶,通过紫外交联制备了结冷胶/PEGDA双网络凝胶,并对单组分凝胶和双网络凝胶的溶胀性能、微观形貌、拉伸力学性能、动态压缩性能和流变性能等进行比较.结果表明,双网络凝胶在类生理环境中具有较小的溶胀率和较好的尺寸稳定性,PEGDA的引入能够大幅度提高结冷胶的韧性,双网络凝胶的拉断伸长率可达340%,断裂能达1.01×103J/m2,与天然关节软骨相当.将成纤维细胞种植在凝胶内部进行体外三维立体培养,结果显示,细胞在凝胶内部生存状态良好,双网络凝胶的细胞负载率高于单网络结冷胶,说明该体系在生物医用领域具有良好的应用前景.     

海藻酸盐-壳聚糖复合微/纳米凝胶研究进展

综述了海藻酸盐-壳聚糖复合微/纳米凝胶研究进展.指出海藻酸盐与壳聚糖的生物相容性、黏附性和降解性良好,以其为原料制备微/纳米凝胶具有方法简便安全、对药物包载效果好等优点,且与常规尺寸凝胶相比分散性和透过性较好.两者复合制备微/纳米凝胶主要采用一步交联、两步交联、自组装等方法,与单一组分凝胶相比优势明显,在药物输送等领域具有良好的应用前景.     

Plasmid DNA hydrogels for biomedical applications

In the last few years, our research group has focused on the design and development of plasmid DNA (pDNA) based systems as devices to be used therapeutically in the biomedical field. Biocompatible macro and micro plasmid DNA gels were prepared by a cross-linking reaction. For the first time, the pDNA gels have been investigated with respect to their swelling in aqueous solution containing different additives. Furthermore, we clarified the fundamental and basic aspects of the solute release mechanism from pDNA hydrogels and the significance of this information is enormous as a basic tool for the formulation of pDNA carriers for drug/gene delivery applications. The co-delivery of a specific gene and anticancer drugs, combining chemical and gene therapies in the treatment of cancer was the main challenge of our research. Significant progresses have been made with a new p53 encoding pDNA microgel that is suitable for the loading and release of pDNA and doxorubicin. This represents a strong valuable finding in the strategic development of systems to improve cancer cure through the synergetic effect of chemical and gene therapy.