Xuanhe Zhao

Highly stretchable and tough hydrogels

Hydrogels are used as scaffolds for tissue engineering, vehicles for drug delivery, actuators for optics and fluidics, and model extracellular matrices for biological studies. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels have achieved stretches in the range 10–20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m−2 (ref. 8), as compared with ∼1,000 J m−2 for cartilage and ∼10,000 J m−2 for natural rubbers. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties; certain synthetic gels have reached fracture energies of 100–1,000 J m−2 (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ∼90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ∼9,000 J m−2. Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels’ toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.

Active scaffolds for on-demand drug and cell delivery

Porous biomaterials have been widely used as scaffolds in tissue engineering and cell-based therapies. The release of biological agents from conventional porous scaffolds is typically governed by molecular diffusion, material degradation, and cell migration, which do not allow for dynamic external regulation. We present a new active porous scaffold that can be remotely controlled by a magnetic field to deliver various biological agents on demand. The active porous scaffold, in the form of a macroporous ferrogel, gives a large deformation and volume change of over 70% under a moderate magnetic field. The deformation and volume variation allows a new mechanism to trigger and enhance the release of various drugs including mitoxantrone, plasmid DNA, and a chemokine from the scaffold. The porous scaffold can also act as a depot of various cells, whose release can be controlled by external magnetic fields.

Method to analyze electromechanical stability of dielectric elastomers

Subject to an electric voltage, a layer of a dielectric elastomer reduces its thickness, so that the voltage induces a high electric field. The positive feedback may cause the elastomer to thin down drastically, resulting in an electrical breakdown. The authors show that the electromechanical instability occurs when the Hessian of the free-energy function ceases to be positive definite. Their calculation shows that the stability of the actuator is markedly enhanced by prestresses, agreeing with existing experimental observations.

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

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.

Maximal energy that can be converted by a dielectric elastomer generator

Mechanical energy can be converted to electrical energy by using a dielectric elastomer generator. The elastomer is susceptible to various modes of failure, including electrical breakdown, electromechanical instability, loss of tension, and rupture by stretch. The modes of failure define a cycle of maximal energy that can be converted. This cycle is represented on planes of work-conjugate coordinates and may be used to guide the design of practical cycles.

Electrostriction in elastic dielectrics undergoing large deformation

We develop a thermodynamic model of electrostriction for elastic dielectrics capable of large deformation. The model reproduces the classical equations of state for dielectrics at small deformation, but shows that some electrostrictive effects negligible at small deformation may become pronounced at large deformation. The model is then specialized to account for recent experiments with an elastomer, where the electric displacement is linear in the electric field when the strain of the elastomer is held fixed, but the permittivity changes appreciably when the strain changes. Our model couples this quasilinear dielectric behavior with nonlinear elastic behavior. We explore the consequence of the model by deriving conditions under which the deformation-dependent permittivity suppresses electromechanical instability.

Electrical breakdown and ultrahigh electrical energy density in poly(vinylidene fluoride-hexafluoropropylene) copolymer

This paper investigates the electrical breakdown of a polar fluoropolymer, poly(vinylidene fluoride-hexafluoropropylene) which exhibits an exceptionally high discharged electrical energy density (>25 J/cm3). It is shown that above room temperature, the breakdown strength decreases with temperature. It is further shown that such a temperature dependence of breakdown strength is consistent with the electromechanical breakdown model by taking into consideration of the plastic deformation of semicrystalline polymers.

A theory of constrained swelling of a pH-sensitive hydrogel†‡

Many engineering devices and natural phenomena involve gels that swell under the constraint of hard materials. The constraint causes a field of stress in a gel, and often makes the swelling inhomogeneous even when the gel reaches a state of equilibrium. This paper develops a theory of constrained swelling of a pH-sensitive hydrogel, a network of polymers bearing acidic groups, in equilibrium with an aqueous solution and mechanical forces. The condition of equilibrium is expressed as a variational statement of the inhomogeneous field. A free-energy function accounts for the stretching of the network, mixing of the network with the solution, and dissociation of the acidic groups. Within a Legendre transformation, the condition of equilibrium for the pH-sensitive hydrogel is equivalent to that for a hyperelastic solid. The theory is first used to compare several cases of homogenous swelling: a free gel, a gel attached to a rigid substrate, and a gel confined in three directions. To analyze inhomogeneous swelling, we implement a finite element method in the commercial software ABAQUS, and illustrate the method with a layer of the gel coated on a spherical rigid particle, and a pH-sensitive valve in microfluidics.

Ultrasound-triggered disruption and self-healing of reversibly cross-linked hydrogels for drug delivery and enhanced chemotherapy

Significance Drug-releasing polymers give clinicians the ability to deliver chemotherapy directly to tumors, sparing the rest of the body from toxic side effects. Most devices deliver a constant, unchangeable drug dose over time. However, we found that cancer cells are more sensitive to short-term, high-dose “bursts” of the chemotherapeutic mitoxantrone than to constant doses over longer periods, suggesting a benefit for implantable devices that allow external control over dose and timing. Biocompatible, injectable alginate hydrogels displayed the ability to self-heal damage induced by ultrasound pulses, enabling on-demand delivery of mitoxantrone, in vitro and in vivo, and mitoxantrone-loaded gels implanted near tumors were more effective at eliminating tumor growth when a daily pulse of ultrasound was applied. Biological systems are exquisitely sensitive to the location and timing of physiologic cues and drugs. This spatiotemporal sensitivity presents opportunities for developing new therapeutic approaches. Polymer-based delivery systems are used extensively for attaining localized, sustained release of bioactive molecules. However, these devices typically are designed to achieve a constant rate of release. We hypothesized that it would be possible to create digital drug release, which could be accelerated and then switched back off, on demand, by applying ultrasound to disrupt ionically cross-linked hydrogels. We demonstrated that ultrasound does not permanently damage these materials but enables nearly digital release of small molecules, proteins, and condensed oligonucleotides. Parallel in vitro studies demonstrated that the concept of applying temporally short, high-dose “bursts” of drug exposure could be applied to enhance the toxicity of mitoxantrone toward breast cancer cells. We thus used the hydrogel system in vivo to treat xenograft tumors with mitoxantrone, and found that daily ultrasound-stimulated drug release substantially reduced tumor growth compared with sustained drug release alone. This approach of digital drug release likely will be applicable to a broad variety of polymers and bioactive molecules, and is a potentially useful tool for studying how the timing of factor delivery controls cell fate in vivo.

Formation of creases on the surfaces of elastomers and gels

When a block of an elastomer is bent, the compressed surface may form a crease. The critical strain for creasing measured experimentally is known to disagree with that predicted by linear perturbation analysis. This paper calculates the critical strain by comparing the elastic energy in a creased body and that in a smooth body. This difference in energy is expressed by a scaling relation. Critical conditions for creasing are determined for elastomers subject to general loads and gels swelling under constraint. The theoretical results are compared with existing experimental observations.