Marine mussels are a model for improving strength, stretchiness and adhesion in hydrogels for wound healing

Credit: Pixabay/CC0 public domain
Hydrogels are all around. Hydrogels are water-loving polymers which can absorb and retain water. They can be found in everyday consumer products like soft contact lenses, disposable diapers and certain foods. Due to their biocompatibility, they can eventually degrade and then be absorbed back into the body.

These properties allow hydrogels mimic living tissue to aid in tissue regeneration or replacement. The most important of these uses is to heal wounds. Hydrogels can be used to heal wounds because they are able to hydrate and create a supportive environment. This allows for healing processes such as blood vessel formation, tissue breakdown, activation and pain relief.

Because of their biosafety, gelatin methacryloyl hydrogels (GelMA), are highly recommended for wound healing. Their inherently poor mechanical properties, such as their limited stretchiness, relative stiffness, inflexibility and inability to stick to tissue surfaces, make it difficult to use them. These characteristics can be improved by experimenting with different preparation methods and components.

A gelMA hydrogel can be prepared by dissolving gelatin in water. The result is a dispersion in the water of gelatin polymer chain chains. The solution is then treated with a chemical called a "photo-initiator", which makes the polymer chain sticky and allows them stick together. The photo-initiators are activated by UV light. Polymer chains cross-link with each other to form networks. This is where hydrogels are formed. Water molecules can enter the network and stretch the chains, thereby locking them in place.

You can modify the properties of the gel by either adding chemicals to bind to the polymer chains prior to UV exposure or changing the parameters to adjust the gel's properties. These modifications were used in the past to improve GelMA's physical characteristics.

Another approach was to add additional chemicals to the GelMA solution prior crosslinking. The resultant chemically conjugated Hydrogel showed slight improvements in tissue adhesion. Another approach to strengthening GelMA was to reinforce flexible, thin chemically conjugated GelMA film films with additional chemicals. However, GelMA hydrogels still have challenges in improving three of the mechanical properties of toughness and stretchiness as well as adhesive strength.

Researchers from the Terasaki Institute of Biomedical Innovation have developed a method that simultaneously improves the strength, stretchiness, and adhesive abilities of GelMA hydrogels. Credit: Khademhosseini Laboratory

The Terasaki Institute for Biomedical Innovation has collaborated to develop methods for improving these properties in GelMA Hydrogels using a simple process with tunable fabrication parameters.

In their quest to improve adhesion in hydrogels, the researchers first looked to nature for an example. The strong threads produced by marine mussels can be used to attach and pull ropes to rocks and other irregular surfaces. The mussels create adhesion proteins in an acidic environment. After exposure to slightly alkaline ocean waters, these proteins undergo a chemical reaction that stimulates thread formation.

To increase GelMA's strength, stretchiness and adhesive properties, the TIBI group added large amounts of dopamine to GelMA in a similar fashion. The gelMA adhesive strength was further increased by the team using alkaline conditions.

These results revealed that large amounts of dopamine could be added to GelMA solution to increase its stretchiness by nearly sixfold, and its strength by over threefold. Another experiment showed that dopamine can be strengthened up to fourfold when it is exposed to alkaline conditions prior to crosslinking. Its resistance to shear forces can also be increased by nearly sevenfold.

Hossein Montazarian (Ph.D.), first author of this project, stated that the experiments provided valuable insights into methods for activating toughness in GelMA-based gelgels.

Researchers will continue to explore other chemicals in order to improve GelMA's mechanical properties. This could lead to further improvements in other applications, such as skin-attachable devices and healing and regenerative inner implants.

Ali Khademhosseini Ph.D., TIBI CEO, stated that "the knowledge gained here about the fundamental mechanical characteristics of hydrogels could have far-reaching consequences on biomedical applications." It is just one example of the many impactful research that our biomaterials platform has done.

Hossein Montazerian et. al., Stretchable and Bioadhesive Gelatin Methacryloyl Based Hydrogels Enabled By in Situ DopaminePolymerization, ACS Applied Materials & Interfaces (2021). Journal information: ACS Applied Materials and Interfaces Hossein Montazerian et al, Stretchable and Bioadhesive Gelatin Methacryloyl-Based Hydrogels Enabled by in Situ Dopamine Polymerization,(2021). DOI: 10.1021/acsami.1c10048

Terasaki Institute for Biomedical Innovation