Injectable Extracellular Matrix-Inspired Hemostatic Hydrogel Composed of Hyaluronan and Gelatin with Shear-Thinning and Self-Healing.

Injectable ECM-inspired hydrogels composed of hyaluronic acid and gelatin are biocompatible and potentially useful for various medical applications. We developed injectable hydrogels composed of monoaldehyde-modified hyaluronic acid (HA-mCHO) and carbohydrazide-modified gelatin (GL-CDH), "HA/GL gel", whose ratios of HA-mCHO to GL-CDH were different. The hydrogels exhibited gelation times shorter than 3 s. In addition, the hydrogels showed strong shear-thinning and self-healing properties, mainly because of the dynamic covalent bonding of Schiff bases between HA-mCHO and GL-CDH. This hydrogel degraded in the mice's peritoneum for a week and showed excellent biocompatibility. Moreover, the hydrogel showed a higher breaking strength than fibrin glue in the lap shear test of porcine skin. Finally, the hydrogels decreased bleeding to as low as fibrin glue without using thrombin and fibrinogen in a mouse liver bleeding model in both single- and double-barreled syringe administrations. HA/GL gels have the potential for excellent biocompatibility and hemostasis in clinical settings.

Injectable, Shear-Thinning, Self-Healing, and Self-Cross-Linkable Benzaldehyde-Conjugated Chitosan Hydrogels as a Tissue Adhesive.

Benzaldehyde-conjugated chitosan (CH-CBA) was synthesized by a coupling reaction between chitosan (CH) and carboxybenzaldehyde (CBA). The pH-sensitive self-cross-linking can be achieved through the Schiff base reaction. The degree of substitution (DS) of CH-CBA was controlled at 1.4-12.7% by optimizing the pH and reagent stoichiometry. The dynamic Schiff base linkages conferred strong shear-thinning and self-healing properties to the hydrogels. The viscosity of the 2 wt/v % CH-CBA hydrogel decreased from 5.3 × 107 mPa·s at a shear rate of 10-2 s-1 to 2.0 × 103 mPa·s at 102 s-1 at pH 7.4. The CH-CBA hydrogel exhibited excellent biocompatibility in vitro and in vivo. Moreover, the hydrogel adhered strongly to porcine small intestine, colon, and cecum samples, comparable to commercial fibrin glue, and exhibited effective in vivo tissue sealing in a mouse cecal ligation and puncture model, highlighting its potential as a biomaterial for application in tissue adhesives, tissue engineering scaffolds, etc.

Tri-branched gels: Rubbery materials with the lowest branching factor approach the ideal elastic limit.

Unlike hard materials such as metals and ceramics, rubbery materials can endure large deformations due to the large conformational degree of freedom of the cross-linked polymer network. However, the effect of the network's branching factor on the ultimate mechanical properties has not yet been clarified. This study shows that tri-branching, which entails the lowest branching factor, results in a large elastic deformation near the theoretical upper bound. This ideal elastic limit is realized by reversible strain-induced crystallization, providing on-demand reinforcement. The enhanced reversible strain-induced crystallization is observed in the tri-branched and not in the tetra-branched network. A mathematical theory of structural rigidity is used to explain the difference in the chain orientation. Although tetra-branched polymers have been preferred since the development of vulcanization, these findings highlighting the merits of tri-branching will prompt a paradigm shift in the development of rubbery materials.

Temperature Dependence of Polymer Network Diffusion.

The swelling dynamics of polymer gels are characterized by the (collective) diffusion coefficient D of the polymer network. Here, we measure the temperature dependence of D of polymer gels with controlled homogeneous network structures using dynamic light scattering. An evaluation of the diffusion coefficient at the gelation point D_{gel} and the increase therein as the gelation proceeds ΔD≡D-D_{gel} indicates that ΔD is a linear function of the absolute temperature with a significantly large negative constant term. This feature is formally identical to the recently discovered "negative energy elasticity" [Y. Yoshikawa et al. Phys. Rev. X 11, 011045 (2021)PRXHAE2160-330810.1103/PhysRevX.11.011045], demonstrating a nontrivial similarity between the statics and dynamics of polymer networks.

Structure-property relationship of a model network containing solvent.

For the application of polymer gels, it is necessary to control independently and precisely their various physical properties. However, the heterogeneity of polymer gels hinders the precise control over the structure, as well as the verification of theories. To understand the structure-property relationship of polymer gels, many researchers have tried to develop a homogeneous model network. Most of the model networks were made from polymer melts that did not have a solvent and had many entanglements in the structure. Because the contribution of entanglements is much larger than that of chemical crosslinking, it was difficult to focus on the crosslinking structure, which is the structure considered in conventional theories. To overcome such a situation, we have developed a new model network system that contains much solvent. Specifically, we fabricated the polymer gel (Tetra-PEG gel) by mixing two types of solutions of tetra-armed poly(ethylene glycol) (Tetra-PEG) with mutually reactive end groups (amine (-PA) and activated ester (-HS)). Because the existence of a solvent strongly reduces the effect of entanglements, the effect of the crosslinking structure on the physical properties can be extracted. In this review, we present the structure-property relationship of Tetra-PEG gel. First, we show the structural homogeneity of Tetra-PEG gels. Then, we explain gelation reaction, elastic modulus, fracture energy and kinetics of swelling and shrinking of Tetra-PEG gels by comparing the theories and experimental results.

Three cooperative diffusion coefficients describing dynamics of polymer gels.

Cooperative diffusion coefficient (Dcoop) describes the dynamics of a polymer network in a gel, and is estimated by three independent methods. We measured three Dcoop's of a model polymer network system (Tetra-PEG gels), and obtained the experimental evidence to fundamentally understand the dynamics of polymer gels.