A new review suggests that the next generation of biomedical hydrogels could be designed less like uniform gels and more like precisely engineered miniature landscapes, with organized structures that control how forces, water, ions, drugs and biological signals move through the material. Published in Supramolecular Materials, the study argues that the internal architecture of a hydrogel may be just as important as its chemical ingredients—and could determine whether the material succeeds or fails in demanding medical and electronic applications.

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

Tags: advanced polymer network designbioelectronic interface materialsBiomedical hydrogel designcontrolled drug delivery hydrogelsforce and signal transmission in soft materialshierarchical hydrogel structuresmechanically resilient biomedical gelsmolecular building blocks in hydrogelsstructure-property relationships in hydrogelssupramolecular hydrogel architecturetissue engineering hydrogelswater transport in hydrogels