PROVIDENCE, R.I. [Brown University] — Biomedical engineers from Brown University have developed a new wound dressing material that releases antibiotic drugs only when harmful bacteria are present in a wound. In a new study, the researchers show that the material could help rapidly clear wound infections to accelerate healing while reducing the unnecessary use of antibiotics — a major driver of antibiotic resistance and hard-to-treat "superbug" infections that claim tens of thousands of lives worldwide each year.
The new material is a smart hydrogel loaded with an antibiotic cargo that can be placed directly on a wound under a bandage. The hydrogel is sensitive to an enzyme produced by many different types of harmful bacteria. When the enzyme is present, the hydrogel starts to degrade, releasing the antibiotics trapped inside. But when no harmful bacteria are present, the hydrogel stays intact, safely locking its antibiotic cargo away.
"Antimicrobial resistance is a major problem worldwide, so we need better approaches for how we use antibiotics," said Anita Shukla, a professor in Brown's School of Engineering who led the development of the smart hydrogel. "We've developed a material that releases antibiotics only when harmful bacteria are present, so it limits exposure to antibiotics when they're not needed but still provides these important medications when they are needed."
For the study, which is published in Science Advances, the researchers put their hydrogel material to the test, showing that it is highly selective to the presence of the enzymes produced by common wound infection-causing bacteria, and that it may promote better infection clearance and wound healing compared to a hydrogel dressing commonly used in clinical settings today.
Hydrogels are Jell-O-like materials made largely of water and long, spaghetti-like polymer molecules. The polymers are held together by smaller molecules called crosslinkers, which keep the hydrogel intact. For this new material, the researchers used a crosslinker that degrades when it comes into contact with enzymes called beta-lactamases, which are produced by a wide variety of bacteria. That degradation allows the hydrogel structure to fall apart and release the antibiotic cargo inside.
In petri dish experiments, the researchers confirmed that the material only degraded when harmful, beta-lactamase-producing bacteria were present. When only harmless bacteria that do not produce beta-lactamases were present, the material stayed intact and did not lead to antibiotic resistance development over a long-term exposure to the hydrogel dressing.
That selectivity for beta-lactamases is critical, the researchers said. Confirming beta-lactamase specificity means that release of antibiotics only happens in the presence of harmful infection-causing bacteria, and exposure to the healthy skin microbiota can be greatly reduced.
The study also showed that until degradation is triggered, the material holds on tightly to its antibiotic cargo.
"This really is a very stable formulation that doesn't allow the drug to leach out," Shukla said. "It's truly trapped in there until there is a significant amount of beta-lactamase production that can cause hydrogel degradation."
In a series of experiments in mice, the researchers showed that a single application of the hydrogel could fully eradicate bacterial infection in an abrasion wound. The new material also outperformed an antimicrobial dressing that's commonly used today in both bacterial eradication and wound healing.
Taken together, the results suggest a promising new way to fight wound infections while conserving critical antibiotics. Studies suggest that more than 1 million people worldwide die each year as a result of infections that are resistant to common antibiotics. The problem is expected to get worse, nearing 10 million annual deaths associated with antimicrobial resistance by 2050, if steps are not taken to reduce antibiotic overuse.
"Our findings suggest that these bacterial enzyme-responsive smart hydrogels have the potential to provide targeted, on-demand infection eradication while minimizing unnecessary exposure to antibiotics," the researchers conclude. "By releasing the antibiotic only in the presence of beta-lactamase-producing bacteria, our hydrogel system provides effective treatment while minimizing susceptibility to antibiotic resistance."
The research team has patented the new material and is working toward further advancement of the technology for potential future commercialization.
The work was supported by the Dr. Ralph and Marian Falk Medical Research Trust.
