Improving strength, stretchiness and adhesion in hydrogels for wound
healing
Scientists use the adhesive capabilities of mussels as a model for
optimizing hydrogels' mechanical properties

Date:
August 30, 2021
Source:
Terasaki Institute for Biomedical Innovation
Summary:
Scientists use the adhesive capabilities of mussels as a model for
simultaneously optimizing the strength, stretchiness and adhesion
of GelMA hydrogels, a feat not obtained in previous attempts.



FULL STORY ========================================================================== Hydrogels are everywhere. They are water-loving polymers which can absorb
and retain water and can be found in such everyday consumer products
such as soft contact lenses, disposable diapers, certain foods, and even
in agricultural applications. They are also extremely useful in several
medical applications due to their high degree of biocompatibility and
their ability to eventually degrade and be reabsorbed into the body.


========================================================================== These qualities allow hydrogels to simulate living tissue for tissue replacement or regeneration. One of the most useful of these applications
is for healing wounds. Hydrogels are ideal for this purpose, with their
ability to hydrate and form a moist and supportive environment. This facilitates processes beneficial for wound healing, such as blood vessel formation, the breakdown of dead tissue, activation of immune cells, the prevention of live cell and tissue death and even the alleviation of pain.

Natural hydrogels, particularly gelatin methacryloyl (GelMA) hydrogels,
are favored for wound healing due to their biosafety and exceptional biocompatibility. But their usage is hampered by their inherently
poor mechanical properties such as limited stretchiness, relative
brittleness and inflexibility, and their inability to adhere to onto
tissue surfaces. In order to improve upon these characteristics,
variations on preparation methods and components have been attempted.

When a GelMA hydrogel is prepared, a solution of gelatin is made by
mixing and dissolving gelatin in water. This results in a dispersion of
gelatin polymer chains in the water. A chemical called a photo-initiator
is then added to the solution, which makes the polymer chains sticky and
allows them to stick to one another. Exposure to UV light activates the photo-initiators and the polymer chains cross-link to each other to form
a network. Water molecules enter this network, stretching the chains and becoming locked within them; this illustrates the hydrogels' absorptive
powers and is the point where gelation, or solidification, occurs.

The properties of this gel can be modified by adding chemicals that bind
to the polymer chains before UV exposure, or the UV parameters themselves
can be varied to tune the gel's properties. Some of these modifications
have been experimented with in previous attempts to improve GelMA's
physical properties.

One approach was to introduce additional chemicals into the GelMA solution before crosslinking; the resultant chemically conjugated hydrogel showed
a slight improvement in tissue adhesion. Other attempts have been made at strengthening GelMA by reinforcing flexible thin chemically conjugated
GelMA films with additional chemicals. But challenges remain with
improving the three mechanical properties of toughness, stretchiness,
and adhesive strength simultaneously in GelMA hydrogels.



==========================================================================
A collaborative team from the Terasaki Institute for Biomedical Innovation (TIBI) has developed methods for improving all three of these properties
in GelMA hydrogels in a simple procedure with tunable fabrication
parameters.

The researchers first turned to an example found in nature in their
approach to improving adhesion in the hydrogels. Marine mussels secrete
strong threads that are used as attachments and pulling ropes on rocks
and other irregular surfaces. To form these threads, the mussels produce adhesion proteins in an acidic environment; upon exposure to the slightly alkaline ocean water, the proteins undergo a chemical change which spurs
thread formation.

In a corresponding fashion, the TIBI team added large quantities of
dopamine, a chemical analog to mussel adhesion protein, to GelMA to
increase its strength, stretchiness, and adhesive properties. They also subjected the mixture to alkaline conditions to further increase the
GelMA's adhesive strength.

The results showed that the addition of large quantities of dopamine
to the GelMA solution could increase the stretchiness of the
resultant hydrogel by almost six-fold and its strength by more than
three-fold. Other experiments showed that when the dopamine is subjected
to alkaline conditions before the crosslinking step, the adhesive strength could be increased up to four times and its resistance to shear forces
by almost seven-fold.

"The experiments we have conducted provide valuable insight into
procedures for activating toughness and adhesion in GelMA-based
hydrogels," said Hossein Montazarian, Ph.D., first author of the project.

The researchers will continue to experiment with other chemicals to
optimize their effects on GelMA's mechanical properties. This can lead to improvements in additional applications such as skin-attachable wearable devices or healing and regenerative internal implants.

"The knowledge gained here on the fundamental mechanical properties of hydrogels can have far-reaching effects on biomedical applications,"
said Ali Khademhosseini, Ph.D., TIBI's Director and CEO. "It is one of
many examples of impactful research from our biomaterials platform."
This work was supported by funding from the National Institutes of Health (1R01EB023052-01A1, 1R01HL140618-01).

========================================================================== Story Source: Materials provided by Terasaki_Institute_for_Biomedical_Innovation. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Hossein Montazerian, Avijit Baidya, Reihaneh Haghniaz, Elham
Davoodi,
Samad Ahadian, Nasim Annabi, Ali Khademhosseini, Paul S. Weiss.

Stretchable and Bioadhesive Gelatin Methacryloyl-Based Hydrogels
Enabled by in Situ Dopamine Polymerization. ACS Applied Materials &
Interfaces, 2021; DOI: 10.1021/acsami.1c10048 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210830163949.htm

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