RESEARCH

 
Tetra Gel

A hydrogel is a three-dimensional polymer network containing water as a solvent. It has a structure similar to that of living soft tissues. Due to such similarities, we expect to apply hydrogels as a biomaterial used in vivo.

  • Hydrogel, made by Toyoichi Tanaka

  • Ronnie Coleman, from his instagram


Biomaterials are required to realize various functions in vivo. Controlling the physical properties of hydrogels is essential for the design of truly useful biomaterials.

To control the physical properties of the hydrogels, precise control of the network structures is necessary. However, conventional polymer networks have a heterogeneous network structure, making it challenging to control hydrogels' physical properties.
 
Heterogeneous network structure

We succeeded in designing the hydrogel with an extremely uniform structure. Specifically, we synthesized two types of tetra-armed polymers with mutually reactive functional groups and made hydrogels from them. We named this hydrogel consisting of four-branched Polyethyleneglycol (PEG) Tetra gel.

Tetra gel is a model system for revealing the correlation between structure and physical properties due to its simple design. One of our primary goals is to investigate hydrogels' structure and physical properties and strengthen the theoretical system of gels.
 

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Make hydrogel

Please think of jelly, a type of hydrogel. You can somehow realize that hydrogel has solid-like and liquid-like properties.

A hydrogel, however, does not flow, which is clear evidence of a solid. Thus, when making a gel, since it is a liquid that is not originally a gel, the liquid becomes a solid. This change is called sol-gel transition, or simply gelation.

Since it is a liquid before gelation, it can be taken out of a syringe or placed in a mold to transform it into any shape. On the other hand, after gelation, it becomes solid and cannot be taken out of the syringe or deformed significantly. For example, when necessary to mold a hydrogel, if the gelation time is too early, the time required for molding will not be available.
When using a hydrogel to stop bleeding, the solution will flow before it hardens if the gelation time is too long. That is, we need to control the gelation time appropriately.




Besides, the biocompatibilities of the constitutive polymers and the gelation reaction are crucial for fabricating hydrogels in vivo.
Furthermore, it is essential to control the solution's viscosity before gelation to apply hydrogel to the tissue surface appropriately.
Controlling gelation is an essential factor in hydrogels' practical application.
One of our primary objectives is to control gelation without impairing the controllability of physical properties.


 

Cure with hydrogel

There are many roles that hydrogels can play in the body. For example, "release the drug," "become a cell scaffold," or "replace soft tissue." In any role, it is at least necessary not to damage the surrounding tissues.

For biosafety, it is necessary to use a chemical substance that is less irritating to the living body. Still, it is also essential to consider the effects of the physical properties on the living body.

One of them is the stiffness (elastic modulus) of the hydrogel. The gel needs to have a modulus close to that of the surrounding tissue.  It can damage the surrounding tissue if it is much stiffer than the surrounding tissue.

The other is the swelling pressure of the hydrogel. Water is abundant in our bodies. Hydrogels generally tend to swell in water. Thus, we should take care of it when using gels, especially in confined spaces. The swelling pressure is high enough to damage surrounding tissue.
 
Highly stretchable hydrogels

As you see, even for biosafety, we should take care of the hydrogel's physical properties. For practical use, it is necessary to control the higher-order functions such as the controlled release of substances, promoting cell growth, and maintaining high mechanical properties while ensuring safety. It is impossible to make a gel with the desired function by ad hoc design.

To control these functions independently, we investigate the correlation among the network structure, the physical properties, and functions. We start by constructing a theoretical system of the hydrogel.

Recently, it is becoming possible to make gels with complicated functions, such as "Nonswellable Hydrogel Without Mechanical Hysteresis."





 

Disintegrate the hydrogel

Let's think about what happens after the hydrogel is inserted into the body.
For example, when we use the hydrogels as artificial cartilage or a cell scaffold in regenerative medicine.
Will it remain in the body in the same state for the rest of its life?
It does not.
Hydrogels are gradually damaged in the body, swell progressively, and finally dissolve.
Generally speaking, hydrogels break down through this mechanism called bulk degradation.
For this reason, the effects of gel degradation must always be considered when thinking about long-term use.

On the other hand, there are cases where the hydrogel does not need to be present in the body for very long, for example, in wound dressing, anti-adhesion, and cell scaffolding.
In these cases, the material will disintegrate within a week to six months. Especially in cell scaffolds, it is ideal that they break down in synchronization with cell proliferation.

From these examples, controlling the degradability of the hydrogel is extremely important.
Precise control of the degradability of hydrogels is one of our primary goals.


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