Injuries could be treated more efficiently with a dressing that releases medication as soon as an infection starts in a wound. Empa researchers are currently working on polymer fibers that soften as soon as the environment heats up due to an infection, thereby releasing a germicidal agent.
It is not possible to tell from the outside whether a wound will heal smoothly under the dressing or whether bacteria will penetrate the injured tissue and cause inflammation. To be on the safe side, disinfectant ointments or antibiotics are therefore applied to the wound before a dressing is applied. However, these preventative measures are not always necessary. As a result, medication is wasted and wounds are "over-treated".
Worse still, the wasteful use of antibiotics promotes the development of multi-resistant germs, which represent a huge problem in global healthcare. Empa researchers from the two Empa laboratories "Biointerfaces" and "Biomimetic Membranes and Textiles" in St. Gallen want to change this. They are developing a bandage that autonomously administers antibacterial drugs only when they are actually needed. The idea of the interdisciplinary team led by Qun Ren and Fei Pan: the bandage should be "loaded" with medication and also react to environmental stimuli. "In this way, wounds could be treated precisely and at the right moment," explains Fei Pan. The team chose a well-known effect as an environmental stimulus: the rise in temperature in an infected, inflamed wound.
Perfect mixture
The team now had to design a material that would react appropriately to this rise in temperature. A skin-compatible polymer composite made from several components was developed for this purpose: Acrylic glass (polymethyl methacrylate, PMMA for short), which is used for spectacle lenses and in the textile industry, for example, and Eudragit, a biocompatible polymer mixture that is used to coat tablets, for example. Electrospinning was used to process the plastic mixture into a fine membrane of nanofibers. Finally, octenidine could be encapsulated in the nanofibers as a medically effective component. Octenidine is a disinfectant that acts quickly against bacteria, fungi and some viruses. In medicine, it can be used on the skin, on mucous membranes and to disinfect wounds.
Signs of inflammation as a trigger
Empa researcher Fei Pan is working on a membrane made of nanofibers that only releases medication when the material heats up (Photos: Empa)The Greek physician Galen described the signs of inflammation back in ancient times. The five Latin technical terms are still valid today: dolor (pain), calor (warming), rubor (redness), tumor (swelling) and functio laesa (limited function) are the classic signs of inflammation. In an infected skin wound, the local warming can be up to five degrees. This temperature difference can be used as a trigger: Suitable materials change their consistency in this area and can release therapeutic substances.
Splintering glove
"To ensure that the membrane acts as a 'smart bandage' and actually releases the disinfectant when the wound heats up due to an infection, we put together the polymer mixture of PMMA and Eudragit in such a way that we were able to set the glass transition temperature appropriately," says Empa researcher Fei Pan. This is the temperature at which a plastic changes from a solid consistency to a rubbery-tough state. The effect is often described metaphorically in reverse: If you place a rubber glove in liquid nitrogen at minus 196 °C, it changes its consistency and becomes so hard that you can shatter it like glass with a single blow.
The desired glass transition temperature of the polymer membrane, on the other hand, was in the region of 37 °C. When inflammation occurs and the skin heats up above its normal temperature of 32-34 °C, the polymer changes from its solid to a softer state. In laboratory experiments, the team was able to observe how the disinfectant is released from the polymer at 37 °C, but not at 32 °C. Another advantage is that the process is reversible and can be repeated up to five times, as the process always "switches itself off" when it cools down. Following these successful tests, the Empa researchers now want to fine-tune the effect. Instead of a temperature range of 4-5 °C, the smart bandage should then switch itself on and off at smaller temperature differences.
Smart and gentle
Further laboratory experiments are now underway to investigate the effectiveness of the nanofiber membranes against wound germs. Team leader Qun Ren has long been working on germs that settle in the boundary layers between surfaces and the environment, such as on a skin wound. "In this biological setting, a kind of no man's land between the body and the dressing material, bacteria find a perfect biological niche," says the Empa researcher. Infectious pathogens such as staphylococci or Pseudomonas bacteria can cause severe wound healing disorders here. It was precisely these wound germs that the team allowed to make the acquaintance of the smart dressing in the Petri dish. And indeed: the number of bacteria was reduced by a factor of 1000 when octenidine was released from the smart dressing.
"With octenidine, we have achieved a 'proof of principle' for the controlled release of medication through an external stimulus," says Qun Ren. In the future, the technology could also be used for other types of medication, which could increase the efficiency and precision of their dosage.
The smart association
Empa researchers are working in interdisciplinary teams on various approaches to improve medical wound treatment. For example, liquid sensors on the outside of the dressing should make it visible when a wound is healing poorly by changing color. Critical glucose and pH values serve as biomarkers here.
In order to combat bacterial infections directly in the wound, the researchers are also working on a polymer foam loaded with anti-inflammatory substances and a skin-friendly membrane made from plant material. The cellulose membrane is equipped with antimicrobial protein building blocks and kills bacteria extremely efficiently in laboratory tests.
In addition, digitalization can achieve more economical and efficient dosages in wound care: Empa researchers are developing digital twins of the skin that allow the course of therapy to be controlled and predicted using real-time modeling.
