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In nature, many structures arise spontaneously because small building blocks attract and join each other. Think of the way proteins fold into a fixed shape, or how cells organize themselves into tissue. Scientists use this principle to create so-called supramolecular materials. These are materials built from small building blocks that can arrange themselves into larger structures without being forced to do so.

The ultimate goal of these kinds of materials is use in medicine: mimicking the body's own tissue, influencing the immune system, releasing drugs, or supporting wound healing. In her research, Craenmehr studied the materials at different scales, from tiny fibers to soft gels.

A versatile building block: UPy

A large part of the research centered on a specific building block: ureido-pyrimidinone, abbreviated as UPy. What makes UPy molecules special is that they interact very well with each other. As a result, they can spontaneously grow into fibers and soft gels in water. These soft, water-rich gels are called hydrogels, and they resemble certain tissues in the body. This makes them interesting for applications where you want to mimic the body's own tissue.

To allow UPy materials to also communicate with cells in the body, Craenmehr equipped them with biological molecules. This is called biofunctionalization. She investigated two ways to attach UPy molecules to proteins. The first method attached UPy at multiple random locations on a protein. The second method was far more precise: UPy was attached at exactly one fixed location on the protein. Both methods worked, but each had its own advantages and disadvantages.

Small protein fragments as signal senders

Full proteins are powerful, but they also make the material more complex to produce and understand. Craenmehr therefore turned her attention to shorter variants: mimetic peptides. These are small fragments of protein that can deliver one specific biological signal, such as a signal that prompts cells to grow or attach.

An important finding was that these peptides only worked well when they were presented through a supramolecular structure. The way a peptide was presented to a cell, and how closely the peptides were spaced on the material, determined whether a cell actually responded to it. This showed that not only the content of the material matters, but also how it is structured.

Two new types of hydrogels

In addition to the UPy systems, Craenmehr also developed two new types of supramolecular hydrogels.

The first type was fully synthetic, meaning it was built entirely from artificial molecules with no biological components. From the many variants tested, two promising hydrogels were selected. These were studied in depth, from their smallest molecular building blocks to the behavior of the material as a whole. Craenmehr then tested whether they could hold onto small particles with antibacterial properties and release them slowly. This turned out to be possible.

The second type of hydrogel was inspired by a protein that occurs naturally in the body: apolipoprotein A1. This protein has a distinctive shape and a specific distribution of water-attracting and water-repelling parts. These properties served as inspiration for a new, adaptable peptide hydrogel system. Craenmehr investigated how different modifications to the molecule affected self-assembly and function. She then examined the material at multiple scales and tested whether it could release molecules in a controlled way. A first experiment in living systems was also carried out.

Many routes to smart biomaterials

Finally, Craenmehr brought together all the strategies investigated: fully synthetic materials, materials linked to proteins or peptides, and materials that mimic natural systems. Together, they showed how many different routes exist for designing functional biomaterials.

The insights from this research help in better tailoring supramolecular materials to specific medical applications. In this way, fundamental laboratory research brings the development of smarter, more body-friendly materials for medicine one step closer.

This research was conducted within ICMS (Institute for Complex Molecular Systems) at Eindhoven University of Technology, in the Biomedical Materials and Chemistry research group led by Patricia Dankers. The research was funded by DARTBAC (NWA.1292.19.354).

The PhD thesis will be available as open access from June 5, 2027.