Researchers at the Technical University of Munich (TUM) have developed hollow microspheres made of mucus and polydopamine using a simple and scalable production method. These tiny spheres are intended to serve as packaging for therapeutic substances, for example in joints or on the oral mucosa. Their properties and mode of action can be adjusted by the choice of materials and are also influenced by the surrounding biological environment.
Andreas Heddergott / TUM Oliver Lieleg, Professor of Biopolymer Materials, and his team are harnessing the diverse properties of mucins - the key components of the natural linings such as those found in the oral mucosa or the stomach - to create technological solutions in biomedicine. Their latest development is a multifunctional microsphere made of mucin and polydopamine. The microsphere is designed to enable a retarded release of molecular cargoes at body sites where adhesion of such drug carriers is otherwise difficult, such as on the oral mucosa or on cartilage.
This good adhesion has been tested on animal tissue and is brought about by the strong adhesive properties of polydopamine. At the same time, mucin adds valuable features: it renders the spheres more adjustable regarding their pore size, and allows them to act as a natural lubricant. "In joints, for example, this could help prevent damage created by joint movements. It may also provide a protective coating on injured tissue in the mouth, another advantage in addition to the microspheres' function as drug delivery agents" explains Di Fan, first author of the study.
The hollow spheres are easy to produce, load, and seal
Production of the new hollow spheres starts with an established process: a core is first coated with the desired materials and then removed, leaving behind a hollow structure. With other materials, the spheres sometimes shrink or even collapse when the core is dissolved. In contrast, the microspheres made from polydopamine and mucin remain structurally stable. Their surface is porous. This allows the cargo to be added after microsphere production and to enter the spheres by diffusion, as shown with model cargo molecules in the study.
The next step is new and crucial: the researchers apply an additional component to the surface, which partially seals the shells of the spheres. This helps keep more of the cargo inside the sphere after loading while ensuring that it is gradually released over time. A range of materials can be used for this locking step, but the approach proved particularly effective with silver ions - positively charged atoms of silver.
Protect or destroy: how material selection and the biological setting determine the effect
The choice of sealing material for sealing is also crucial for the effects of the microspheres. "If silver ions are used, the microspheres help kill cells. This could be particularly useful in treating tumors," says Di Fan, who demonstrated different effects in cell cultures.
In contrast, without silver ions, the anti-inflammatory properties of polydopamine take effect and protect cells from chemical stress instead. This is especially useful in tissue suffering from inflammation, with potential applications in cases such as osteoarthritis or chronic wounds. Both the type of sealing agent used and the biological setting influence how quickly the cargo is released.
"With the hollow microsphere system, we have created a versatile drug release system that is easy to produce, scalable, and adaptable," explains project leader Lieleg. "Our chosen combination of mucin and polydopamine brings together many advantages offered by those biomolecules that go beyond the typical tasks of a classical drug release system; for example, it can protect or eliminate cells - depending on the envisioned application."
Di Fan, Chiara Gunnella, Yukun Wang, Luca Reichert, Pedro Henrique da Rosa Braun, Jan Torgersen, Oliver Lieleg: Multi-Functional Polydopamine-Mucin Hollow Particles Provide Tunable Shell Permeability, ROS Scavenging, Tissue Adhesion, and Lubricity for Biomedical Applications. Small (2025). https://doi.org/10.1002/smll.202503238
- Oliver Lieleg is Professor of Biopolymer Materials at the TUM School of Engineering and Design .
- He conducts research at the TUM Center for Functional Protein Assemblies (CPA ) and the Munich Institute of Biomedical Engineering (MIBE) at TUM.
- MIBE is an Integrative Research Institute where researchers specializing in medicine, the natural sciences, engineering, and computer science join forces to develop new methods for preventing, diagnosing or treating diseases. The activities cover the entire development process - from the study of basic scientific principles through to their application in new medical devices, medicines and software.
