Hybrid Double-network Hydrogels Research Articles

Acrylic-grafted nanocellulose hybrid double-network hydrogel with super-high toughness for water shutoff treatments

Hydrogels with high strength are strongly needed to perform such operations as fluid plugging and water shutoff in the oil & gas industry. In this work, a new type of tough hydrogel consisting of the acrylic acid grafted nanocellulose network and the copolymer (AA-co-AM) network was synthesized via one-pot free-radical polymerization, and further cross-linked by using Al3+. The prepared dual-crosslinked double network hydrogel (DN-Poly-X-CNF-g-AA) showed the high compressive strength and toughness at low concentrations of nanocellulose (within 0.2 wt%), i.e., the maximum compressive strength was 2.5 MPa at strains of 90% and the recovery rates exceeded to 90% after 10 compressive cycles. Meanwhile, the grafted nanocellulose endowed the double-network hydrogels with the strong intermolecular forces and the well-ordered hierarchical structure, which exhibited a high thermal decomposition temperature, solid-like elastic behavior and a swelling suppression. Finally, the sand-pack plugging experiments showed that the double-network hydrogels could effectively plug the porous media with different permeability, in which the breakthrough pressure gradient was between 4.9 and 104.63 MPa/m. The results demonstrated that the obtained tough hydrogel has a great potential to be applied as soft materials for water shutoff and conformance control in reservoirs.

Fabrication and Characterization of π-π Stacking Peptide-Contained Double Network Hydrogels.

Since the physical properties are similar to native extracellular matrices, double network (DN) hydrogels have been studied extensively in the tissue engineering. However, the double chemical crosslinked DN hydrogel is limited by poor fatigue resistance. π-π stacking is a non-covalent bonding interaction, which is essential to maintain and self-assemble the three-dimensional structure of biological proteins and nucleic acids. In this study, a robust polyethylene glycol diacrylate (PEGDA)/FFK hybrid DN hydrogel was prepared by Michael addition and π-π stacking. The hybrid DN hydrogels with π-π stacking interactions have excellent mechanical strength and fatigue resistance. The DN FFK/PEGDA hydrogels reveal great biocompatibility and hemocompatibility. The DN hydrogels containing π-π stacking have the potential to fabricate robust hybrid DN hydrogels in drug release and tissue engineering.

Mechanoresponsive Drug Loading System with Tunable Host-Guest Interactions for Ocular Disease Treatment.

Conventional administration of eye drops often requires high dosages and/or repetitive treatments to achieve therapeutic efficacy. This is inefficient and may result in side effects or even toxicity. Although many delivery systems of ophthalmic drugs have been reported, most of them work in a fixed format in which both the type and dose of the loaded drugs cannot be changed upon demand. To overcome this limitation, a hybrid double network hydrogel system composed of methacryloyl gelatin, pluronic F127 diacrylate, and β-cyclodextrin-modified oxidized dextran was developed. The hydrogels presented good mechanical strength and biocompatibility. In vitro assessments demonstrated that the hydrogels loaded with commonly used ophthalmic drugs could sustain the drug release for more than 21 days. This hydrogel system exhibited features of mechanoresponsive drug loading, and the capacity of drug loading could be significantly enhanced by macroscopically mechanical compression. Further in vivo evaluation of the drug delivery capacity showed that a dexamethasone-loaded hydrogel as a fornix insert effectively suppressed upregulation of proangiogenic factors and suture-induced corneal neovascularization in rats. This novel hydrogel system represents a promising drug delivery platform, which could potentially improve the treatments of ocular surface and other diseases.

Articular Cartilage-Inspired Hybrid Double-Network Hydrogels with a Layered Structure and Low Friction Properties

Articular Cartilage-Inspired Hybrid Double-Network Hydrogels with a Layered Structure and Low Friction Properties

Fmoc-phenylalanine as a building block for hybrid double network hydrogels with enhanced mechanical properties, self-recovery, and shape memory capability

Based on thermoreversible sol–gel transitions of simple amino acid, fluorenylmethoxycarbonyl-modified phenylalanine (Fmoc-F), a hybrid double-network (DN) hydrogel, has been fabricated by combining a self-assembled Fmoc-F gel and a covalent polyacrylamide (PAAm) network. Up to 2 wt% Fmoc-F can be incorporated into DN hydrogels (90 wt% water) to form thinner and shorter nanofibers within the PAAm gel network than in pure Fmoc-F hydrogels; this indicates strong interaction between two gelators. Fmoc-F self-assembly also provides sacrificial bonding to effectively dissipate stretching energy, resulting in increased tensile modulus and yield strength of DN gels by 3437% and 737%, respectively, when compared with pure PAAm hydrogel. The relatively small increase of 133% and 177% in tensile strain and strength, respectively, of DN gels could be attributed to the time-independent discontinuous dissociation of the Fmoc-F self-assembly for energy dissipation. DN hydrogels also exhibit temperature-sensitive shape memory and self-recovery performance because of thermoreversible Fmoc-F self-assembly. • A novel DN gel was prepared by introducing thermoreversible Fmoc-F self-assembly into PAAm hydrogel. • A reinforcing mechanism of DN gel was proposed. • Energy dissipation mechanism mainly depends on discontinuous dissociation of Fmoc-F self-assembly. • DN gels exhibit temperature-sensitive shape memory and self-recovery performance.

Hybrid double-network dual-crosslinked hydrogel with self-healing ability and mechanical stability. Synthesis, characterization and application for motion sensors

The growing list of potential applications of soft materials increases the demand for, among others, new multifunctional hydrogels. We propose a hybrid double-network hydrogel based on synthetic poly(acrylic acid) and alginate, a natural polymer. These polymer networks were double crosslinked: chemically and physically. The ferrous ion was used to catalyze the decomposition of the initiator and later, after its oxidation by the initiator to the ferric ion, was coordinated by the carboxylic groups of the polymer networks and acted as a physicochemical crosslinker. The composition of the hydrogel was optimized to get improved mechanical and electrical properties, and the self-healing ability. The introduction of the coordination bond between Fe3+ and the carboxylic groups of AA and alginate molecules created the ability of self-healing of the hydrogels; they could regenerate without any external stimulus and regain their electrical conductivity and mechanical properties.

Structural aspects controlling the mechanical and biological properties of tough, double network hydrogels

Anticipating an increasing demand for hybrid double network (DN) hydrogels in biomedicine and biotechnology, this study evaluated the effects of each network on the mechanical and biological properties. Polyethylene glycol (PEG) (meth)acrylate hydrogels with varied monomer molecular weights and architectures (linear vs. 4-arm) were produced with and without an added ionically bonded alginate network and their mechanical properties were characterized using compression testing. The results showed that while some mechanical properties of PEG single network (SN) hydrogels decreased or changed negligibly with increasing molecular weight, the compressive modulus, strength, strain to failure, and toughness of DN hydrogels all significantly increased with increased PEG monomer molecular weight. At a fixed molecular weight (10 kDa), 4-arm PEG SN hydrogels exhibited better overall mechanical performance; however, this benefit was diminished for the corresponding DN hydrogels with comparable strength and toughness and lower strain to failure for the 4-arm case. Regardless of the PEG monomer structure, the alginate network made a relatively larger contribution to the overall DN mechanical properties when the covalent PEG network was looser with a larger mesh size (e.g., for larger monomer molecular weight and/or linear architecture) which presumably enabled more ionic crosslinking. Considering the biological performance, adipose derived stem cell cultures demonstrated monotonically increasing cell area and Yes-associated protein related mechanosensing with increasing amounts of alginate from 0 to 2 wt.%, demonstrating the possibility for using DN hydrogels in guiding musculoskeletal differentiation. These findings will be useful to design suitable hydrogels with controllable mechanical and biological properties for mechanically demanding applications. Statement of significanceHydrogels are widely used in commercial applications, and recently developed hybrid double network hydrogels have enhanced strength and toughness that will enable further expansion into more mechanically demanding applications (e.g., medical implants, etc.). The significance of this work is that it uncovers some key principles regarding monomer molecular weight, architecture, and concentration for developing strong and tough hybrid double network hydrogels that would not be predicted from their single network counterparts or a linear combination of the two networks. Additionally, novel insight is given into the biological performance of hybrid double network hydrogels in the presence of adipose derived stem cell cultures which suggests new scope for using double network hydrogels in guiding musculoskeletal differentiation.

A high-strength, toughness, self-recovery hydrogel for potential osteochondral repair

Many load-bearing tissues, such as osteochondral and meniscus, show high strength, toughness and rapid recovery. However, incorporating these mechanical properties into similar biomimetic synthetic biomaterials is a fundamental challenge. Here, we demonstrate a strong, tough and self-recovery hydrogel employing double network (DN) strategy and multiple dynamic interactions (such as metal coordination, hydrogen bond, etc.). The hybrid DN hydrogel exhibited remarkable compressive strength of 3.74 MPa, elongation of 418.92%, fracture energy of 9.41 kJ·m−2, excellent cytocompatibility and self-recovery, so it has a great application prospect in osteochondral repair.

Hybrid double-network hydrogel for highly stretchable, excellent sensitive, stabilized, and transparent strain sensors

Nowadays, great effort has been devoted to fabricate flexible wearable sensor with high stretchability, moderate modulus, favorable durability, excellent transparency, and satisfactory sensitivity. In this work, we report the preparation of a hybrid double-network (DN) hydrogel by a simple one-pot method. First, chitosan was added into an AlCl3 solution to form Al3+-chitosan complex (CS-Al3+). Second, the hybrid CS/Al3+-poly(acrylamide) (PAM) DN hydrogels were constructed via in situ polymerization of acrylamide (AM) in present of Al3+-chitosan complex. Thanks to the existence of electrically conductive CS-Al3+ networks, the resulting hybrid DN hydrogel exhibits excellent stretchability, fatigue resistance, transparency, and conductivity. Furthermore, the CS/Al3+-PAM DN hydrogel could be used as strain sensor, and demonstrates many desired virtues, including satisfactory sensitivity (gauge factors of 1.7–12.1), wide detection range (up to 1500%), low limit of discernment (1% strain), high reliability, and excellent durability (1000 cycles). More significantly, the manufactured hydrogel-based strain sensor can be employed as wearable devices to precisely detect various human movements.

A multiscale polymerization framework towards network structure and fracture of double-network hydrogels

Double-network (DN) hydrogels, consisting of two contrasting and interpenetrating polymer networks, are considered as perhaps the toughest soft-wet materials. Current knowledge of DN gels from synthesis methods to toughening mechanisms almost exclusively comes from chemically-linked DN hydrogels by experiments. Molecular modeling and simulations of inhomogeneous DN structure in hydrogels have proved to be extremely challenging. Herein, we developed a new multiscale simulation platform to computationally investigate the early fracture of physically-chemically linked agar/polyacrylamide (agar/PAM) DN hydrogels at a long timescale. A “random walk reactive polymerization” (RWRP) was developed to mimic a radical polymerization process, which enables to construct a physically-chemically linked agar/PAM DN hydrogel from monomers, while conventional and steered MD simulations were conducted to examine the structural-dependent energy dissipation and fracture behaviors at the relax and deformation states. Collective simulation results revealed that energy dissipation of agar/PAM hydrogels was attributed to a combination of the pulling out of agar chains from the DNs, the disruption of massive hydrogen bonds between and within DN structures, and the strong association of water molecules with both networks, thus explaining a different mechanical enhancement of agar/PAM hydrogels. This computational work provided atomic details of network structure, dynamics, solvation, and interactions of a hybrid DN hydrogel, and a different structural-dependent energy dissipation mode and fracture behavior of a hybrid DN hydrogel, which help to design tough hydrogels with new network structures and efficient energy dissipation modes. Additionally, the RWRP algorithm can be generally applied to construct the radical polymerization-produced hydrogels, elastomers, and polymers.

Double-network hydrogels with superior self-healing properties using starch reinforcing strategy

Constructing hybrid double network (DN) hydrogels has become an important strategy to prepare strong and tough hydrogels with good self-healing properties for durable usage. However, the recoverable and self-healing efficiencies of DN hydrogels are usually low. We develop a type of hybrid DN hydrogel, which contain the starch network for generating strong dynamic interactions within the gel matrix. The composite gels show tensile strength over 200 kPa with the elastic modulus of ∼29.7 kPa. Gelatinization of cassava starch is a key procedure that can significantly raise mechanical strengths. The healing efficiency of the composite gel gradually increased to as high as 99 % after 24 h at room temperature. This work shows that dynamic physical bonding in hydrogels can be greatly enhanced by a simple starch reinforcing tactic. The combination of naturally abundant starch with hydrophilic polymers provides a general approach to design functional soft materials for applications in various fields.

Functionalizing Double-Network Hydrogels for Applications in Remote Actuation and in Low-Temperature Strain Sensing.

Multifunctional hydrogels have important applications in various fields such as artificial muscles, wearable devices, soft robotics, and tissue engineering, especially for those with favorable mechanical properties, good low-temperature resistance, and stimuli-responsive capabilities. In the current study, a type of polyacrylamide/sodium alginate/carbon nanotube (PAAm/SA/CNT) double-network (DN) hydrogel was fabricated, which exhibited a high tensile strength of 271.68 ± 6.04 kPa, a favorable conductivity of 1.38 ± 0.17 S·m-1, and a good self-healing ability under heating conditions. In addition, the composite hydrogel exhibited controllable photomechanical deformations under near-infrared irradiation, such as bending, swelling, swimming, and object grasping. To further broaden the applications of the hydrogel in low-temperature environments, calcium chloride (CaCl2) was introduced into such a PAAm/SA/CNT DN hydrogel as an additive. Interestingly, the tensile/compressive strengths as well as elasticity were well-maintained at a temperature as low as -20 °C. In addition, the PAAm/SA/CNT/CaCl2 hydrogel presented excellent conductivity, recoverability, and strain-sensing capability under such extreme conditions. Overall, the investigations conducted in this paper have provided potentially new methods and inspirations for the generation of multifunctional PAAm/SA/CNT/CaCl2 hybrid DN hydrogels toward extended applications.

κ-Carrageenan/poly(N-acryloyl glycinamide) double-network hydrogels with high strength, good self-recovery, and low cytotoxicity

Due to their high mechanical properties and recoverability, hybrid double-network (DN) hydrogels composed with a physically cross-linked network (the first network) and a chemically cross-linked network (the second network) arouse researchers’ interest and attention in various fields. In this work, we have fabricated hybrid double-network hydrogels with ionically cross-linked κ-carrageenan as the first network and covalently cross-linked poly(N-acryloyl glycinamide) (PNAGA) as the second network by using an one-pot method. Because of synergistic interaction between κ-carrageenan and PNAGA polymer chains, the hybrid DN hydrogels exhibit excellent mechanical properties with a breaking stress of 1.7 MPa and a breaking strain of 250%, which are much better than their parent single-network hydrogels. In addition, due to the physical cross-links among κ-carrageenan and PNAGA, the hybrid DN hydrogels show good self-healing ability; and due to the biocompatibility of all components, the hybrid DN hydrogels show low cytotoxicity. All those properties endow the potential application of κ-carrageenan/PNAGA DN hydrogel in bioengineering.

Hybrid double-network hydrogels with excellent mechanical properties

Fabrication of high performance hybrid double-network hydrogels via electrostatic interactions.

Simultaneously improved strength and toughness in κ-carrageenan/polyacrylamide double network hydrogel via synergistic interaction

Hybrid double network (DN) hydrogels have been fabricated by combining a physically cross-linked κ-carrageenan network, where various cations were used as cross-linker, with a covalently cross-linked polyacrylamide (PAAm) network. Compared to monovalent K+ and divalent Ca2+ cations, the presence of K+/Ca2+ mixture cations produced a well interconnected porous structure due to the synergistic effect, which simultaneously improved the strength and toughness of the resulting DN hydrogel. A model has been proposed considering the dissociation asynchronism of double-helical aggregates, which well interpret the fracture process and toughening mechanism of the K+/Ca2+-cross-linked κ-carrageenan/PAAm DN hydrogel. Moreover, the synergistic effect of K+/Ca2+ mixture cations also improved the recovery efficiency at room temperature and self-healing ability of DN hydrogel. The strategy of synergistic interaction presented here provides an alternative view for the fabrication of hybrid DN hydrogels with desirable mechanical performance and functional property.

Antibacterial and Antifouling Hybrid Ionic-Covalent Hydrogels with Tunable Mechanical Properties.

Because of their self-recovery ability and fatigue resistance, double-network (DN) hydrogels with hybrid ionical-covalent cross-linking have received wide attention. In this work, by a simple "one-pot" method, a novel kind of hybrid ionic-covalent chitosan/poly(sulfobetaine methacrylate) (CS/PSBMA) DN hydrogels was prepared. The hydrogels showed high tensile strength (2.0 MPa), strong elastic modulus (0.5 MPa), fast self-recovery ability as well as excellent fatigue resistance, high mechanical strength, and toughness retention rate after soaking in water for 24 h. Additionally, the mechanical properties of the DN gels were enhanced after stretch and relaxation because of the rearrangement of the CS network. More excitingly, because of the antifouling feature of PSBMA and the inherent antibacterial property of CS, the hybrid DN hydrogels demonstrated a "repel and kill" effect on microorganisms. The CS/PSBMA DN hydrogels may find potential applications in biomedical fields, such as artificial connective tissues, implantable devices, and wound dressing.

Fabrication and mechanical behaviors of novel supramolecular/polymer hybrid double network hydrogels

Double network hydrogels (DN gels) are one of most extensively investigated high strength hydrogels. However, most of DN gels are concern to macromolecules, low-molecular-weight gelators (LMWG)-based supramolecular hydrogels are rarely reported to fabricate recoverable DN gels. Owing to the low mechanical properties, LMWG-based supramolecular hydrogels are hardly fabricated as conductive materials for human motion monitoring. Herein, we report a general strategy to fabricate strong, tough and conductive cholate-based supramolecular gels with double network (DN) structure (i.e. La-cholate/PAAm DN gels), consisting of La-cholate supramolecular gel as first network and covalent polyacrylamide gel (PAAm gel) as second network, in which La-cholate supramolecular gel was self-assembled by La3+ ions and sodium cholate under sonication via the synergistic effect of hydrogen bonds, hydrophobic interactions and metal-coordination. At optimal condition, La-cholate/PAAm DN gel exhibited high tensile properties (fracture stress of 0.314 MPa, fracture strain of 29.85 mm/mm, elastic modulus of 90 kPa, and work of extension of 5.678 MJ/m3) and high toughness (tearing energy of 1098 J/m2), which are comparable to conventional chemical or hybrid DN gels. Meanwhile, La-cholate/PAAm DN gel also showed rapid self-recovery property (stiffness recovery of 84% and toughness recovery of 46% after resting for 3 min) at room temperature and λ-dependent luminescent property under UV-light. More importantly, cholate-based supramolecular gels with DN structure could be prepared with various metal ions and monomers. Interestingly, our cholate-based DN gels were ionically conductive, which could be used as strain sensor to finely detect the human motions. We hope our design principles, along with the simple method and cholate-based DN gels, can be generally applied to develop a new generation of strong and tough LMWG-based supramolecular hydrogels with various functionalities.

High strength of hybrid double-network hydrogels imparted by inter-network ionic bonds.

Interaction between networks has been proven to be of importance for mechanical property enhancement of double-network (DN) hydrogels. In this work, inter-network ionically cross-linked hybrid DN hydrogels have been prepared using poly(sodium 2-acrylamide-2-methylpropanesulfonate) (PNaAMPS) as the first network, and a co-polymer of a cationic monomer and acrylamide (AM) as the second network. Ionic complexes were formed between the two oppositely charged networks after dialyzing the hydrogels in water. Near the ion-balance point, hybrid DN hydrogels with enhanced strengths were achieved compared to the unmodified PNaAMPS/polyacrylamide (PAM) DN hydrogel. Synchrotron radiation small-angle X-ray scattering (SAXS) analyses were performed on the DN hydrogels. It was found that large and compact cross-linked domains were formed in the hybrid DN hydrogels, especially near the ion-balance point, as demonstrated by the SAXS results. These large and compact cross-linked domains, which indicate enhanced interactions between networks containing ionic bonds besides physical entanglements, dissipate additional concentrated stress, resulting in high strength of the hybrid DN hydrogels.

In situ bone regeneration enabled by a biodegradable hybrid double-network hydrogel.

Stem cell therapy based on advanced biomaterials provides a promising strategy in bone tissue engineering. Nevertheless, guided bone regeneration which fulfills the criteria in terms of biomechanics, biodegradability and bioactivity is highly appealing but challenging. Inspired by the superior double-network (DN) structure, herein, a biodegradable hybrid DN hydrogel is proposed to promote in situ bone regeneration. The DN hydrogel is constructed by interspersing a methacrylated gelatin (GelMA) network into a well-defined nanocomposite (NC) hydrogel consisting of methacrylated chitosan (CSMA) and polyhedral oligomeric silsesquioxane (POSS) via a two-step photo-crosslinking process. The hybrid DN hydrogel has the following advantageous characteristics: (i) it exhibits enhanced stiffness and toughness benefiting from the inorganic POSS units and unique energy dissipation; (ii) naturally occurring biomacromolecules (chitosan and gelatin) as the hydrogel framework result in an appropriate biodegradation behavior, which can be replaced by newly formed tissues; (iii) it preferentially guides mesenchymal stem cells (MSCs) toward osteogenic differentiation in vitro by detecting the elevated levels of enzyme activity and calcium deposition along with the up-regulated osteogenesis-related genes and proteins; and (iv) accelerated in situ bone regeneration is observed after implanting MSC-loaded hydrogels into rat calvarial defects. Therefore, we provide a new insight to develop functional hydrogels for triggering specific cellular responses toward stem cell therapy and bone-related tissue engineering.

Dual Physically Cross-Linked κ-Carrageenan-Based Double Network Hydrogels with Superior Self-Healing Performance for Biomedical Application.

Chemically linked double network (DN) hydrogels display extraordinary mechanical attributes but mostly suffer from poor self-healing property and unsatisfactory biocompatibility due to the irreversible breaks in their chemical-linked networks and the use of toxic chemical cross-linking agents. To address these limitations, we developed a novel κ-carrageenan/polyacrylamide (KC/PAM) DN hydrogel through a dual physical-cross-linking strategy, with the ductile, hydrophobically associated PAM being the first network, and the rigid potassium ion (K+) cross-linked KC being the second network. The dual physically cross-linked DN (DPC-DN) hydrogels with optimized KC concentration exhibit excellent fracture tensile stress (1320 ± 46 kPa) and toughness (fracture energy: 6900 ± 280 kJ/m3), comparable to those fully chemically linked DN hydrogels and physically chemically cross-linked hybrid DN hydrogels. Moreover, because of their unique dual physical-cross-linking structures, the KC/PAM hydrogels also demonstrated rapid self-recovery, remarkable notch-insensitivity, self-healing capability, as well as excellent cytocompatibility toward stem cells. Accordingly, this work presents a new strategy toward fabricating self-repairing DPC-DN hydrogels with outstanding mechanical behaviors and biocompatibility. The new type of DN hydrogels demonstrates strong potentiality in many challenging biomedical applications such as artificial diaphragm, tendon, and cartilage.