Yuki Akagi

“Nonswellable” Hydrogel Without Mechanical Hysteresis

Optimizing Injectable Hydrogels Injectable hydrogels are showing promise as scaffolds in regenerative medicine because they can be injected in liquid form and transform in situ into the gel state. However, when exposed to ionic solutions, such as those found in the body, hydrogels can increase in volume by a factor of 2, which can weaken the material. Kamata et al. (p. 873) added a thermoresponsive component to a hydrogel so that the thermoresponsive component would tend to collapse in shape when heated and counteract the hydrogels tendency to swell. Indeed, the resulting gel retained its unswollen volume following immersion in a physiological solution and retained its mechanical strength during repeated stretching or compression. Addition of a thermoresponsive component to a hydrogel counters its tendency to swell and improves its mechanical properties. Hydrogels are three-dimensional polymer networks that contain a large amount of water inside. Certain hydrogels can be injected in solution and transformed into the gel state with the required shape. Despite their potential biomedical applications, the use of hydrogels has been severely limited because all the conventional hydrogels inevitably “swell” under physiological conditions, which drastically degrades their mechanical properties. We report the synthesis of injectable “nonswellable” hydrogels from hydrophilic and thermoresponsive polymers, in which two independently occurring effects (swelling and shrinking) oppose each other. The hydrogels can endure a compressive stress up to 60 megapascals and can be stretched more than sevenfold without hysteresis. Our results demonstrate that the suppression of swelling helps retain the mechanical properties of hydrogels under physiological conditions.

Highly Elastic and Deformable Hydrogel Formed from Tetra-arm Polymers

After decades of efforts by many researchers, we have succeeded in realizing a near-ideal polymer network. This network, the Tetra network, is made by cross-end-coupling of tetra-arm polymer modules. The mechanical energy dissipation was extremely low (tan δ ≈ 10(-4) ). The macroscopic stress-strain relationship of the Tetra network was in good agreement with that of microscopic elastic blobs. The maximum breaking strength was extremely high (≥27 MPa). These results indicate that the Tetra network is closer to an ideal polymer network than any other conventional model networks. Because the Tetra network can be treated as uniformly packed elastic blobs, it should help apply the knowledge of single polymer chains seamlessly to the design of polymer materials and help further develop the theory of rubber elasticity.

Fracture energy of polymer gels with controlled network structures

We have investigated the fracture behaviors of tetra-arm polyethylene glycol (Tetra-PEG) gels with controlled network structures. Tetra-PEG gels were prepared by AB-type crosslink-coupling of mutually reactive tetra-arm prepolymers with different concentrations and molecular weights. This series of controlled network structures, for the first time, enabled us to quantitatively examine the Lake-Thomas model, which is the most popular model predicting fracture energies of elastomers. The experimental data showed good agreement with the Lake-Thomas model, and indicated a new molecular interpretation for the displacement length (L), the area around a crack tip within which the network strands are fully stretched. L corresponded to the three times of end-to-end distance of network strands, regardless of all parameters examined. We conclude that the Lake-Thomas model can quantitatively predict the fracture energy of polymer network without trapped entanglements, with the enhancement factor being near 3.

Autonomous viscosity oscillation by reversible complex formation of terpyridine-terminated poly(ethylene glycol) in the BZ reaction

Autonomous viscosity oscillation by the reversible complex formation of terpyridine-terminated PEG and/or terpyridine-terminated TetraPEG in the BZ reaction was achieved. The BZ reaction induces the periodical binding/dissociation of the Ru–terpyridine complex and causes periodical molecular changes to result in viscosity changes.

Effect of swelling and deswelling on the elasticity of polymer networks in the dilute to semi-dilute region

The Obukhov model is known as the model describing the dependence of the elastic modulus of polymer networks on the concentration and solvent class. In the Obukhov model, the Panyukov model, which assumed the Hookes law of elasticity, was adopted for describing the elastic energy of a network strand. In this study, we for the first time extended both models from the semi-dilute to concentrated region to the dilute to semi-dilute region. To evaluate the extended model, we used Tetra-PEG gel, which has near-ideal network structure, as a model system. The experimental results are well described by the extended model. It is strongly suggested that the Panyukov model and the Obukhov model are valid in dilute to semi-dilute good solvent systems.

Ultimate elongation of polymer gels with controlled network structure

Tetra-PEG gel, which is a polymer gel with a well-controlled network structure, was utilized to examine the model predicting the ultimate elongation ratio of elastomeric materials, i.e., the Kuhn model. The effect of polymer fraction, degree of polymerization of network strands, and connectivity of the Tetra-PEG gel was discussed. The ultimate elongation ratio was estimated from the stress-elongation curves using the extended Gent model. The ultimate elongation ratio of the Tetra-PEG gels with different structural parameters did not obey the Kuhn model at all. Instead, we proposed a new semi-empirical model predicting the ultimate elongation ratio of Tetra-PEG gel.

Co-lyophilized Aspirin with Trehalose Causes Less Injury to Human Gastric Cells and Gastric Mucosa of Rats

BackgroundAspirin is one of the most popular NSAIDs worldwide because of its anti-inflammatory and anticoagulant effects, and however, gastrointestinal injury remains a major complication. We previously reported co-lyophilized aspirin/trehalose (Lyo A/T) decreased the aspirin-induced gastric lesions in dogs.AimThis study investigated the mechanism of gastroprotective effects of trehalose in vitro and in vivo.MethodsThe apoptotic assays were performed in a human gastric carcinoma cell line, which was treated with aspirin, mixed aspirin/trehalose (Mix A/T) or Lyo A/T. Gastric ulcer severity was examined after oral administration of drugs in rats. In addition, the mucosal tissue apoptotic status in drug-treated rats was evaluated. Molecular dynamics simulations and laser Raman spectroscopy were performed in order to examine the molecular properties of Lyo A/T.ResultsDNA fragmentation was detected in AGS cells that were treated with aspirin and Mix A/T, but not in the Lyo A/T-treated cells. There were fewer apoptotic cells in the Lyo A/T-treated cells than in the other cells. Gastric injury was reduced in rats that received oral Lyo A/T compared with the others, while PGE2 synthesis was equally decreased in all groups. TUNEL assay and immunohistochemistry of cleaved caspase-3 in the mucosal tissues also revealed that Lyo A/T treatment induced less apoptosis than the others. The Lyo A/T spectrum showed clear differences in several Raman bands compared with that of Mix A/T.ConclusionsOur data showed that co-lyophilization of aspirin with trehalose reduced gastric injury, potentially through suppression of aspirin-induced mucosal cell apoptosis while retaining its anti-inflammatory effects.