BACKGROUND Hydrogels are formed through the cross-linking of hydrophilic polymer chains within an aqueous microenvironment. The gelation can be achieved through a variety of mechanisms, spanning physical entanglement of polymer chains, electrostatic interactions, and covalent chemical cross-linking. The water-rich nature of hydrogels makes them broadly applicable to many areas, including tissue engineering, drug delivery, soft electronics, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. The lack of desired dynamic cues and structural complexity within the hydrogels has further limited their functions. Broadened applications of hydrogels, however, require advanced engineering of parameters such as mechanics and spatiotemporal presentation of active or bioactive moieties, as well as manipulation of multiscale shape, structure, and architecture. ADVANCES Hydrogels with substantially improved physicochemical properties have been enabled by rational design at the molecular level and control over multiscale architecture. For example, formulations that combine permanent polymer networks with reversibly bonding chains for energy dissipation show strong toughness and stretchability. Similar strategies may also substantially enhance the bonding affinity of hydrogels at interfaces with solids by covalently anchoring the polymer networks of tough hydrogels onto solid surfaces. Shear-thinning hydrogels that feature reversible bonds impart a fluidic nature upon application of shear forces and return back to their gel states once the forces are released. Self-healing hydrogels based on nanomaterial hybridization, electrostatic interactions, and slide-ring configurations exhibit excellent abilities in spontaneously healing themselves after damages. Additionally, harnessing techniques that can dynamically and precisely configure hydrogels have resulted in flexibility to regulate their architecture, activity, and functionality. Dynamic modulations of polymer chain physics and chemistry can lead to temporal alteration of hydrogel structures in a programmed manner. Three-dimensional printing enables architectural control of hydrogels at high precision, with a potential to further integrate elements that enable change of hydrogel configurations along prescribed paths. OUTLOOK We envision the continuation of innovation in new bioorthogonal chemistries for making hydrogels, enabling their fabrication in the presence of biological species without impairing cellular or biomolecule functions. We also foresee opportunities in the further development of more sophisticated fabrication methods that allow better-controlled hydrogel architecture across multiple length scales. In addition, technologies that precisely regulate the physicochemical properties of hydrogels in spatiotemporally controlled manners are crucial in controlling their dynamics, such as degradation and dynamic presentation of biomolecules. We believe that the fabrication of hydrogels should be coupled with end applications in a feedback loop in order to achieve optimal designs through iterations. In the end, it is the combination of multiscale constituents and complementary strategies that will enable new applications of this important class of materials.

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Advances in engineering hydrogels

It is a challenge to synthesize materials that possess the properties of biological muscles-strong, elastic and capable of self-healing. Herein we report a network of poly(dimethylsiloxane) polymer chains crosslinked by coordination complexes that combines high stretchability, high dielectric strength, autonomous self-healing and mechanical actuation. The healing process can take place at a temperature as low as -20 °C and is not significantly affected by surface ageing and moisture. The crosslinking complexes used consist of 2,6-pyridinedicarboxamide ligands that coordinate to Fe(III) centres through three different interactions: a strong pyridyl-iron one, and two weaker carboxamido-iron ones through both the nitrogen and oxygen atoms of the carboxamide groups. As a result, the iron-ligand bonds can readily break and re-form while the iron centres still remain attached to the ligands through the stronger interaction with the pyridyl ring, which enables reversible unfolding and refolding of the chains. We hypothesize that this behaviour supports the high stretchability and self-healing capability of the material.

A highly stretchable autonomous self-healing elastomer

As swollen polymer networks in water, hydrogels are usually brittle. However, hydrogels with high toughness play critical roles in many plant and animal tissues as well as in diverse engineering applications. Here we review the intrinsic mechanisms of a wide variety of tough hydrogels developed over the past few decades. We show that tough hydrogels generally possess mechanisms to dissipate substantial mechanical energy but still maintain high elasticity under deformation. The integrations and interactions of different mechanisms for dissipating energy and maintaining elasticity are essential to the design of tough hydrogels. A matrix that combines various mechanisms is constructed for the first time to guide the design of next-generation tough hydrogels. We further highlight that a particularly promising strategy for the design is to implement multiple mechanisms across multiple length scales into nano-, micro-, meso-, and macro-structures of hydrogels.

Multi-scale multi-mechanism design of tough hydrogels: building dissipation into stretchy networks

A 3D printable and highly stretchable tough hydrogel is developed by combining poly(ethylene glycol) and sodium alginate, which synergize to form a hydrogel tougher than natural cartilage. Encapsulated cells maintain high viability over a 7 d culture period and are highly deformed together with the hydrogel. By adding biocompatible nanoclay, the tough hydrogel is 3D printed in various shapes without requiring support material.

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3D Printing of Highly Stretchable and Tough Hydrogels into Complex, Cellularized Structures

In many animals, the bonding of tendon and cartilage to bone is extremely tough (for example, interfacial toughness ∼800 J m(-2); refs ,), yet such tough interfaces have not been achieved between synthetic hydrogels and non-porous surfaces of engineered solids. Here, we report a strategy to design tough transparent and conductive bonding of synthetic hydrogels containing 90% water to non-porous surfaces of diverse solids, including glass, silicon, ceramics, titanium and aluminium. The design strategy is to anchor the long-chain polymer networks of tough hydrogels covalently to non-porous solid surfaces, which can be achieved by the silanation of such surfaces. Compared with physical interactions, the chemical anchorage results in a higher intrinsic work of adhesion and in significant energy dissipation of bulk hydrogel during detachment, which lead to interfacial toughness values over 1,000 J m(-2). We also demonstrate applications of robust hydrogel-solid hybrids, including hydrogel superglues, mechanically protective hydrogel coatings, hydrogel joints for robotic structures and robust hydrogel-metal conductors.

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Tough bonding of hydrogels to diverse non-porous surfaces

Hydrogels attract great attention as biomaterials as a result of their soft and wet nature, similar to that of biological tissues. Recent inventions of several tough hydrogels show their potential as structural biomaterials, such as cartilage. Any given application, however, requires a combination of mechanical properties including stiffness, strength, toughness, damping, fatigue resistance and self-healing, along with biocompatibility. This combination is rarely realized. Here, we report that polyampholytes, polymers bearing randomly dispersed cationic and anionic repeat groups, form tough and viscoelastic hydrogels with multiple mechanical properties. The randomness makes ionic bonds of a wide distribution of strength. The strong bonds serve as permanent crosslinks, imparting elasticity, whereas the weak bonds reversibly break and re-form, dissipating energy. These physical hydrogels of supramolecular structure can be tuned to change multiple mechanical properties over wide ranges by using diverse ionic combinations. This polyampholyte approach is synthetically simple and dramatically increases the choice of tough hydrogels for applications.

https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/56662/1/Gong-Manuscript-1.pdf

Physical hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity

https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/44832/1/Saito%20Soft%20Matter%20Article-template100921.pdf

Robust bonding and one-step facile synthesis of tough hydrogels with desirable shape by virtue of the double network structure

Our recent study has revealed that neutral polyampholytes form tough physical hydrogels above a critical concentration Cm,c by forming ionic bonds of wide strength distribution. In this work, we systematically investigate the behavior of a polyampholyte system, poly(NaSS-co-DMAEA-Q), randomly copolymerized from oppositely charged monomers, sodium p-styrenesulfonate (NaSS) and acryloyloxethyltrimethylammonium chloride (DMAEA-Q) without and with a slight chemical cross-linking. A phase diagram of formulation has been constructed in the space of monomer concentration Cm and cross-linker density CMBAA. Three phases are observed for the as-synthesized samples: homogeneous solution at dilute Cm, phase separation at semi-dilute Cm, and homogenous gel at concentrated Cm. Above a critical Cm,c, the polyampholyte forms a supramolecular hydrogel with high toughness by dialysis of the mobile counter-ions, which substantially stabilizes both the intra- and inter chain ionic bonds. The presence of the chemical cross-linker (CMBAA > 0) brings about a shift of the tough gel phase to lower Cm,c. The tough polyampholyte gel, containing ∼50 wt% water, is highly stretchable and tough, exhibits fracture stress of σb ∼ 0.4 MPa, fracture strain of eb ∼ 30, and the work of extension at fracture Wext ∼ 4 MJ m−3. These values are at the level of most tough soft materials. Owing to the reversible ion bonds, the poly(NaSS-co-DMAEA-Q) gels also exhibit complete self-recovery (100%) and high fatigue resistance upon repeated large deformation.

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A phase diagram of neutral polyampholyte – from solution to tough hydrogel

The friction between two like-charged polyelectrolyte gels in pure water is measured by using a normal strain-controlled rheometer with a parallel-plates geometry. The effects of normal stress, gel elasticity and sample thickness on the velocity dependence of friction between the gels are investigated. The frictional stress demonstrates strong velocity dependence (liquid-like) when the gel is soft and thick, while it demonstrates a weak or even no velocity dependence (solid-like) when the gel is rigid and thin. The former is interpreted by a combined mechanism of boundary lubrication and hydrated lubrication, wherein the thickness of the lubricating layer is velocity-independent, due to the formation of an electric double layer at the soft and repulsive interfaces. On the other hand, the latter is interpreted by a combined mechanism of boundary lubrication and elastohydrodynamic lubrication, wherein the thickness of the lubricating layer is velocity-enhanced by the water entrainment during sliding. The friction of the soft, thick sample is related to micro-contact while that of the rigid, thin sample is related to macroscopic geometric effect. This work may contribute to the science of friction between two soft and repulsive interfaces in water.

Shinya Kuroda

Papers

Physical hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity

Robust bonding and one-step facile synthesis of tough hydrogels with desirable shape by virtue of the double network structure

A phase diagram of neutral polyampholyte – from solution to tough hydrogel

Friction between like-charged hydrogels—combined mechanisms of boundary, hydrated and elastohydrodynamic lubrication