Hydrogels are water-rich polymer networks that behave partly like solids and partly like liquids. Their polymer chains form a three-dimensional framework, while the spaces within that framework hold large amounts of water. This combination gives hydrogels a soft, tissue-like character, allowing them to interact with cells and transport dissolved molecules. It also makes them attractive for tissue engineering, controlled drug delivery, wearable sensors and bioelectronic interfaces, where materials must remain flexible while supporting mechanical or electrical functions.

Yet many synthetic hydrogels are produced as randomly crosslinked, structurally uniform networks. In such materials, polymer chains and crosslinks are distributed without a clear organization across different length scales. When the gel is stretched or compressed, stress can become concentrated around weak regions, triggering cracks or permanent deformation. Random structures may also lack continuous pathways for the movement of water, ions or therapeutic compounds. In conductive hydrogels, deformation can interrupt electrical routes, causing signals to weaken or disappear precisely when the material is being used.

The review, led by researchers from Nanjing University, Nanjing University of Information Science & Technology and Nantong University, presents an architecture-based approach to solving these problems. The authors describe “high-order structures” as deliberately organized arrangements that extend from the molecular scale to the nanoscale, mesoscale and overall polymer network. At each level, the structure can influence how the material carries force, transports molecules and communicates with living cells. The central idea is that chemistry supplies the building blocks, while architecture determines how those components cooperate.

At the molecular level, interactions such as hydrogen bonding, electrostatic attraction, metal coordination and host–guest recognition can provide reversible connections between polymer chains. Unlike permanent covalent crosslinks, these dynamic bonds can break under stress and reform afterward, allowing a gel to dissipate energy and recover its shape. When such interactions are incorporated into larger, organized structures, they can create materials that are both tough and adaptable. The network does not simply resist damage; it can redistribute stress and use molecular rearrangement to limit the growth of cracks.

One route highlighted in the review is phase separation, in which chemically different components organize into distinct domains. These domains can act as reinforcing regions, soft energy-dissipating zones or interconnected channels. A carefully controlled phase-separated structure may prevent stress from concentrating at a single point while preserving continuous routes for water and solutes. In a drug-delivery system, for example, the size and connectivity of these domains could influence how quickly a therapeutic molecule diffuses through the gel. In a sensor, the same organization could help maintain stable pathways during repeated stretching.

Molecular self-assembly provides another route to high-order organization. Under the right conditions, small molecules, peptides or polymer segments can spontaneously arrange into fibers, ribbons, sheets or other supramolecular structures. These assemblies may function as internal scaffolds that guide the transfer of mechanical stress through the hydrogel. Because many supramolecular interactions are reversible, the structures can also reorganize in response to force, temperature, pH or chemical signals. This responsiveness could allow a hydrogel to adjust its properties as its environment changes, a feature especially relevant to implanted materials and responsive medical devices.

The review also examines nanocomposite integration and polymer crystallization. Nanoparticles, nanosheets, nanotubes or other nanoscale reinforcements can strengthen a hydrogel network and help preserve conductive or mechanically active pathways. Their effectiveness depends not only on their presence but also on their dispersion, alignment and connection to the surrounding polymer. Polymer crystallization can create strong physical crosslinks that reinforce the gel without eliminating its flexibility. When these strategies are combined with dynamic molecular bonds or phase-separated domains, the resulting material may gain several functions at once: toughness, elasticity, conductivity, controlled transport and biological compatibility.

Such structural control could have a direct impact on emerging technologies. In wearable sensors, an organized hydrogel may maintain electrical continuity while being stretched, twisted or compressed against the body. In bioelectronic interfaces, its mechanical softness could help reduce the mismatch between rigid electronics and living tissue, while its internal pathways support the movement of ions that carry biological signals. For drug delivery, domain structure and network density could be tuned to regulate diffusion and release. In tissue engineering, cells could encounter controlled combinations of stiffness, porosity and biochemical cues rather than the relatively featureless environments offered by many conventional gels.

The researchers caution, however, that high-order architecture also introduces new manufacturing and stability challenges. A structure formed during processing may change when the hydrogel dries, absorbs physiological fluids, encounters oxygen or undergoes repeated loading. Small differences in temperature, mixing, solvent removal or reaction time can alter phase evolution, molecular alignment and crystallinity. These changes may produce large differences in performance, making it difficult to reproduce laboratory results at industrial scale. For clinical translation, manufacturers will need methods that can monitor and control heat transfer, mass transport and structural organization throughout production.

The authors propose that automated experimentation, multiscale modeling and artificial intelligence could help overcome these barriers. By linking processing conditions to molecular organization and final performance, researchers may be able to predict how a hydrogel will behave over time rather than testing each formulation through trial and error. Such tools could accelerate the search for materials that remain stable in the complex chemical and mechanical environment of the human body. The broader message of the review is that biomedical hydrogels should be designed as hierarchical systems, where structure at every scale contributes to function. If that approach can be translated into reliable manufacturing, high-order hydrogels could become tougher, smarter and more versatile platforms for medicine, wearable technology and next-generation bioelectronics.

Subject of Research: Biomedical hydrogels and their hierarchical, high-order internal structures

Article Title: Hydrogel with high-order structures: from hierarchical engineering to flexible biomedical applications

Web References: https://doi.org/10.1016/j.supmat.2026.100140

References: Xue, B. et al., “Hydrogel with high-order structures: from hierarchical engineering to flexible biomedical applications,” Supramolecular Materials, DOI: 10.1016/j.supmat.2026.100140

Image Credits: Hongru Wang, Xuelei Chen, Ying Li, Wenxu Sun, Bin Xue, Yi Cao

Keywords

Hydrogels, supramolecular materials, biomedical materials, hierarchical structures, polymer networks, tissue engineering, drug delivery, wearable sensors, bioelectronics, nanocomposites, molecular self-assembly, phase separation, polymer crystallization, biomaterials, nanotechnology

Hydrogels — soft, water-rich materials that maintain their three-dimensional form — are pivotal in a broad spectrum of medical and personal care applications, including wound dressings, drug delivery patches, contact lenses, and cosmetic formulations. Their ability to closely adhere to biological tissues and serve as reservoirs for therapeutic agents makes them indispensable in advanced healthcare. However, a persistent challenge has been enhancing the toughness and adhesiveness of these gels while tuning their degradation profiles to meet clinical demands. The KAIST team’s breakthrough addresses these issues by revisiting the chemistry of κ-Carrageenan, a sulfate-rich natural polymer harvested from red seaweed, widely recognized for its thickening properties in food products.

The molecular architecture of κ-Carrageenan carries numerous sulfate groups that inherently repel each other due to negative charges, impeding the formation of tightly cross-linked networks. This electrostatic repulsion has historically limited the mechanical robustness and adhesive capacity of κ-Carrageenan hydrogels, constraining their biomedical utility. Recognizing this barrier, the researchers turned to tannic acid, a polyphenolic compound capable of multivalent binding through its galloyl groups. These multiple binding sites enable tannic acid to act as a molecular bridge, potentially neutralizing sulfate group repulsions and reinforcing the hydrogel’s internal network.

Rigorous experimental analyses confirmed that instead of being a hindrance, the sulfate groups serve as critical binding sites for tannic acid, effectively transforming a molecular vulnerability into an asset. This interaction results in a significantly denser and more cohesive gel matrix. Quantitatively, the hydrogel’s storage modulus—a measure of its elasticity and firmness—increased from approximately 294 pascals in pure κ-Carrageenan gels to nearly 1,632 pascals when tannic acid was introduced. This fivefold enhancement reflects a substantial leap in structural integrity, allowing the hydrogel to resist deformation under mechanical stress, a vital characteristic for materials intended to remain intact on dynamic biological surfaces.

Moreover, the study highlighted the versatility of tannic acid’s reinforcing effect, demonstrating that its introduction at any stage of hydrogel formation consistently bolstered the microscopic gel network architecture. This dynamic cross-linking capacity affords flexibility in manufacturing and application, potentially simplifying processes for producing hydrogel devices that require specific mechanical and adhesive profiles.

Perhaps one of the most compelling aspects of this innovation is the simultaneous achievement of rapid biodegradability and strong adhesion—a combination rarely seen in synthetic or natural hydrogels. Simulating the harsh chemical environments of the human stomach and intestines, researchers observed that the tannic acid-enhanced hydrogels degraded timely, ensuring that they would not persist beyond their therapeutic window. Concurrently, these hydrogels exhibited robust adhesion to skin and irregular tissue surfaces, guaranteeing that they remain securely in place during therapeutic intervention, such as wound healing or targeted drug administration.

This balance is especially significant in medical applications where dressings or drug patches must endure bodily movements and moisture without premature detachment, yet degrade completely once their function is fulfilled to avoid secondary procedures or complications. The tannic acid-κ-Carrageenan composite thus portends a new class of bioresponsive polymers that can be finely tuned without extraneous chemical modifications, relying solely on food-grade, naturally derived components.

The research extends beyond the immediate medical domain, offering promising implications for food technology, cosmetic science, and regenerative medicine. By formulating a material platform that leverages biocompatible, antioxidant-rich natural compounds, there is an opportunity to engineer safer, environmentally friendly products that fulfill rigorous functional criteria. Potential applications include edible coatings that protect food or prolong freshness, skin-adhering cosmetic treatments, scaffolds that support tissue regeneration, and vehicles for controlled nutrient or drug release.

Professor Haeshin Lee, leading the research team from KAIST’s Department of Chemistry, emphasized the broader significance of their findings. He remarked that their work provides a paradigm for designing hydrogels whose mechanical properties, adhesiveness, and degradation pathways can be seamlessly orchestrated via natural polymer chemistry. This approach not only reduces reliance on synthetic materials but also aligns with trends toward biocompatibility and sustainability in material science.

Published in the peer-reviewed journal Biomimetics on April 21st, this study, authored by lead researcher Han-Yeol Yang and colleagues, underscores the transformative potential of polyphenol intervention in hydrogel technology. The findings were made possible with funding support from Polyphenol Factory Inc., a KAIST faculty-led startup, reflecting a successful synergy between academic research and industry.

Beyond the compelling technical advancements, this work invites further exploration into other natural polyphenols and polymer combinations to broaden the functionality and applicability of hydrogels. Its integration into practical healthcare solutions could markedly improve patient compliance and therapeutic efficacy, underscoring the pivotal role of interdisciplinary research bridging chemistry, biology, and materials engineering.

In summary, the KAIST team’s innovative use of tannic acid to overcome longstanding physicochemical challenges in κ-Carrageenan hydrogels heralds a new chapter in the design of soft, adhesive biomaterials. This advancement promises to accelerate the development of next-generation wound care products, drug delivery platforms, and biocompatible scaffolds—ushering in a future where natural polymers and bioinspired chemistry harmonize to meet complex medical needs.

Subject of Research: Not applicable

Article Title: Adhesive κ-Carrageenan Hydrogels by Polyphenol Intervention

News Publication Date: June 9, 2023

Web References: http://dx.doi.org/10.3390/biomimetics11040290

References: Yang, H.-Y., Seo, J., Choi, W., Kim, E., Yeo, S., Park, S., & Lee, H. (2023). Adhesive κ-Carrageenan Hydrogels by Polyphenol Intervention. Biomimetics, 11(4), 290. https://doi.org/10.3390/biomimetics11040290

Image Credits: KAIST

Keywords

κ-Carrageenan, tannic acid, hydrogel, adhesion, biodegradation, polyphenols, mechanical strength, biomaterials, wound healing, drug delivery, natural polymers, bioengineering