Biomedical engineers at Brown University have developed a hydrogel-based wound dressing that releases antibiotics only in the presence of infection-causing bacteria, offering a potential new method for treating wound infections while limiting unnecessary use of antibiotic. The research findings, published in Science Advances, show how the team developed a β-lactamase–responsive hydrogel wound dressing that detect enzymes produced by infection-causing bacteria and then trigger localized antibiotic release. The wound dressing remains intact in the absence of these bacterial enzymes but undergoes selective degradation when β-lactamases are present, releasing ciprofloxacin that had been encapsulated in liposomes within the hydrogel matrix.
“Antimicrobial resistance is a major problem worldwide, so we need better approaches for how we use antibiotics,” said senior author Anita Shukla, PhD, 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.”
The need for new ways to treat wound infections is driven by rising rates of antimicrobial resistance. The researchers noted that roughly 50% of wound infections are now resistant to potent antimicrobials such as third-generation cephalosporins and global projections estimate that antibiotic-resistant infections could cause 10 million deaths annually by 2050 if no action is taken.
Current approaches to managing wound infections rely heavily on systemic or topical antibiotics and antimicrobial dressings that release drugs passively. These methods can be indiscriminate, affecting both the pathogens, but also exposing healthy microbiota to antibiotics. “…current clinically used antimicrobial hydrogel dressings predominantly operate via a passive release mechanism, resulting in a lack of precise control over drug delivery and diminished specificity, leading to suboptimal therapeutic outcomes and contributing to the spread of antibiotic-resistant superbugs,” the researchers wrote.
In order to move from a passive approach, the Brown turned to a “smart” hydrogel that responds to β-lactamases, enzymes that produced by many common when wounds become infected. These enzymes are contribute to resistance because they break down β-lactam antibiotics. By using this bacterial feature as a trigger, the researchers designed a method that activates only when harmful bacteria are present.
The design of this method first encapsulates the antibiotic ciprofloxacin in liposomes which is then embedded within the hydrogel. This two-step containment was necessary to prevents passive leakage of the antibiotic. When β-lactamases are present, the hydrogel degrades and releases the liposomes, which then deliver the drug at the infection site.
The Brown team’s approach builds on prior work by other researcher teams to develop stimuli-responsive hydrogels. Earlier methods explored triggers such as pH or reactive oxygen species, but these signals can also appear in noninfected wounds. The researchers instead focused on bacterial enzymes, which provide a more precise signal.
When tested, the investigators showed that their hydrogel remained stable in the absence of infection and released antibiotics only when exposed to β-lactamase-producing bacteria. In laboratory and animal models, including a murine wound infection model, a single application eradicated infection and improved healing outcomes compared to a commonly used silver-based dressing. The researchers wrote that the system “provides a precise, infection-triggered antibiotic delivery platform that can improve the treatment of wound infections and mitigate antimicrobial resistance.”
Being able to both control antibiotic delivery, and limit unnecessary delivery of antibiotics, is tied to how resistance develops. “It is widely recognized that the bactericidal activity of antibiotics is concentration dependent, with higher concentrations achieving optimal therapeutic outcomes, while subinhibitory levels can promote the development of drug resistance and recurrence of infections,” the researchers wrote. Releasing high concentrations only when needed avoids the low-level exposures that can drive resistance.
Next steps to further develop this smart wound dressing include evaluating the hydrogel in chronic and polymicrobial wound settings, where multiple bacterial species interact and biofilms are common. The team also noted the need to test additional antibiotics, assess immune responses, and use clinical bacterial isolates to better reflect real-world infections.
