Hydrogels have attracted considerable attention for applications ranging from wound dressings and drug delivery systems to cosmetics and wearable sensors. While synthetic hydrogels such as polyethylene glycol (PEG) and polyvinyl alcohol (PVA) offer excellent strength and durability, naturally derived hydrogels are particularly appealing for materials intended for human use due to their inherent biocompatibility, low toxicity, and biodegradability.

Kappa-carrageenan (κ-CRG) is a polysaccharide, extracted from red seaweeds, that forms thermo-reversible hydrogels. Widely used as a food thickener and gelling agent, κ-CRG has also attracted interest for applications in drug delivery, wound dressings, and soft tissue engineering. However, these hydrogels are mechanically fragile and have limited resistance to repeated deformation, restricting their use in demanding biomedical and cosmetic environments.

Existing strategies for strengthening κ-CRG hydrogels often rely on salts, additional polymer networks, or complex formulations. While effective, these approaches can compromise the simplicity and naturally derived character of the material.

A new study published in the Open Access journal Biomimetics demonstrates how a plant derived polyphenol, tannic acid (TA), can act as a “molecular glue” to strengthen κ-CRG hydrogels. Using only naturally sourced materials, the researchers demonstrate a previously underexplored strategy for tuning the mechanical robustness and degradation behaviour of these food-grade materials.

Professor Haeshin Lee, lead author of the study, explains:

“This study is an example showing that the mechanical strength, adhesiveness, and degradation behaviour of hydrogel can be designed together using only naturally derived materials,”

Supramolecular chemistry provides a dynamic network

Supramolecular materials are complex materials that are built from discrete, individual building blocks held together by reversible, non-covalent interactions. This allows molecules to spontaneously self-assemble into highly structured architectures with desirable features. Understanding these interactions allows researchers to design smart materials that can be used in a range of fields.

Electrostatic forces are among the most common supramolecular interactions. Much like magnets, oppositely charged regions of different molecules can attract one another, while like charges repel. These dynamic interactions allow materials to self-organize and respond to their environment, making supramolecular chemistry an attractive strategy for designing functional materials.

κ-CRG is structurally similar to agarose, as both polysaccharides share a related galactan backbone. However, κ-CRG contains negatively charged sulfate groups (Figure 1). Hydrogel formation occurs through the assembly of polymer chains into helical structures, which then associate to form a three-dimensional network. The sulfate groups along the κ-CRG backbone generate electrostatic repulsion between neighbouring helices, limiting how closely they can pack together and ultimately reducing the strength of the resulting gel.

Figure 1: A comparison of the molecular structures of both κ-CRG and agarose.

The researchers hypothesized that TA, a plant-derived polyphenol composed of multiple galloyl groups, could act as a “molecular glue”. Through interactions between its galloyl groups and the sulfate groups of κ-carrageenan, TA was expected to bridge neighbouring polymer chains and reinforce the hydrogel network without requiring chemical modification or synthetic crosslinkers.

To test this idea, the team investigated whether these proposed sulfate–galloyl interactions could strengthen the hydrogel network by altering how κ-CRG helices form and associate.

Tannic acid strengthens κ-carrageenan hydrogels

To determine whether the tannic acid was interacting specifically with the sulfate groups of κ-CRG, the researchers compared its behaviour with agarose, a structurally similar polysaccharide that lacks the negatively charged sulfate substituents. Although both materials share a related galactan backbone, they responded differently to the addition of TA.

Even small amounts of TA disrupted the formation of agarose hydrogel, causing the material to become cloudy and form precipitated aggregates. In contrast, κ-CRG retained its transparent gel structure even at much higher TA concentrations.

This difference in outcomes can be explained by preferential TA binding with the sulfate functionalities in κ-CRG. In the presence of sulfate groups, in agarose, TA is thought to associate directly with the polymer backbone. This interaction prevents helices from forming a hydrogel and causes the observed precipitation.

This was further confirmed using infra-red (IR) spectroscopy which revealed shifts in the sulfate-associated bands, supporting the presence of sulfate-galloyl interactions. These insights provide molecular-level evidence that TA was associating with negatively charged sulfate groups along the polymer backbone.

Mechanical testing then proved that these interactions reinforce the hydrogel network. This was done through measuring the storage modulus, which determines a material’s elastic behaviour. As the concentration of TA was increased, the storage modulus of κ-CRG hydrogels rose steadily from 294 Pa for the untreated gel to more than 1600 Pa at the highest TA loading of 15 wt%. This represents a higher than fivefold increase.

Together, these findings support the idea that TA acts as a molecular glue, reducing electrostatic repulsion between neighbouring helices and promoting the formation of a denser, mechanically stiffer hydrogel network.

Valency is the key for strengthened hydrogels

In chemistry, valency refers to the number of interactions a molecule can form at the same time. Molecules with a low valency can bind to only one or a few sites, whereas multivalent molecules contain multiple binding groups that allow them to connect several targets simultaneously. This ability to form many interactions at once often leads to stronger and more cooperative supramolecular networks.

To understand whether the strengthening effect originated from galloyl chemistry alone or from the multivalent structure of TA, the researchers compared TA with pyrogallol, a much smaller molecule containing only a single galloyl unit.

Pyrogallol also strengthened κ-CRG hydrogels, but the effect was considerably smaller than that observed with TA. This indicates that galloyl groups alone can reinforce the network through local sulfate interactions, but the dramatic increase in stiffness requires the multivalent architecture of TA, which can bridge multiple polymer chains simultaneously. This allows it to link multiple chains together to create a denser and mechanically stronger network.

What this means in real-world conditions

Hydrogels used in biomedical and cosmetic applications must withstand exposure to water, dissolved ions, and changing pH conditions. The researchers examined how the modified hydrogels performed in simulated physiological environments, including their ability to adhere to skin as wound-dressing materials.

Pyrogallol-containing hydrogels

• Moderate increase in stiffness.
• Gradual weakening in aqueous environments.
• Limited surface adhesion.

TA-containing hydrogels

• More than fivefold increase in stiffness.
• Faster disintegration under aqueous environments.
• Nearly tenfold higher adhesion strength than native κ-CRG gels.

One of the most striking differences between the two systems was their behaviour on surfaces. Native κ-CRG gels and pyrogallol-containing gels detached readily from rough substrates and skin, whereas TA-containing hydrogels remained firmly attached even under repeated movement. Quantitative testing showed that TA increased adhesion strength by nearly tenfold. The researchers attribute this to exposed galloyl groups at the hydrogel surface, which can form multiple non-covalent interactions with other biological molecules on the skins surface, such as proteins and carbohydrates.

Together, these results show that molecular valency controls more than mechanical strength. By acting as a molecular glue, tannic acid simultaneously influences stiffness, degradation behaviour, and adhesion to biological and synthetic surfaces.

Making smarter hydrogels from natural ingredients

This study demonstrates a novel design principle for tuning hydrogel properties. By using only food-grade natural components and avoiding the addition of synthetic chemicals, the system allows increased gel strength and adhesion within a single material platform. The key insight is that molecular valency can be used as a practical design handle to switch between stable, slowly eroding networks and more dynamic, highly adhesive systems.

Looking forward, this approach has clear potential across a range of bio- and healthcare-related applications. These include capsules and coating materials for foods, skin-adhering cosmetics and skincare products, wound dressings, drug delivery patches, and scaffolds for tissue engineering.

More studies on hydrogels and technologies made from natural products can be found across the Open Access journals Gels and Biomimetics. Alternatively, you can access the full MDPI journal list here.