CHAMPAIGN, Ill. — Newly developed microparticles can infiltrate stubborn bacterial matrices and release tiny oxygen bubbles to clean surfaces and wounds more efficiently than hydrogen peroxide or other cleaning agents alone, researchers at the University of Illinois Urbana-Champaign report. In two papers they demonstrated the bubble-generating particles' ability to clean tenacious biofilms from surgical instruments and, when embedded within bandages, to clean infected wounds and speed healing.
"Biofilms are a dense matrix of bacterial cells and proteins. While sterilizing agents can kill bacteria, the matrix protects them, making it much harder to treat or clean with chemicals. For example, hydrogen peroxide has been used for centuries but only cleanses the surface and does not penetrate the film," said Illinois chemical and biomolecular engineering professor Hyunjoon Kong , the research team's leader. "We take a mechanical approach: Our particles infiltrate the biofilm first and then generate bubbles inside the matrix, disrupting it."
Kong's group developed tiny cylinders made of biosilica coated in manganese dioxide, a catalyst which releases tiny oxygen bubbles when exposed to a hydrogen peroxide solution. The bubbles accumulate within the hollow cylinder, then are released, propelling the microparticles even deeper into the matrix where they continue to produce bubbles, said graduate student Joo Hun Lee, the first author of the first paper. The researchers watched the bubbles form and rupture, the particles move and biofilm disperse using high-speed cameras and Optical Coherence Tomography in collaboration with Stephen Boppart , a U. of I. professor of bioengineering and professor of biomedical and translational sciences in the Carle Illinois College of Medicine .
As well as describing the microparticles in the first paper, published in the journal ACS Applied Materials and Interfaces, the researchers demonstrated the microparticles' ability to clean stubborn biofilms from surgical instruments.
While the standard method of cleaning surgical tools involves enzymatic detergents combined with autoclaving — a process using steam at high heat and pressure — biofilms can stubbornly cling to tiny crevasses or serrations in the tools, Lee said.
The Illinois team compared the biofilms remaining within the serrations of surgical instruments after the typical protocol with those remaining after treatment with the microparticles. They found a similar or better efficacy with the microparticles. As an additional boost, the microparticle cleaning can be combined with autoclaving, Kong said.
"We show a five-fold reduction in remaining biofilm with our particles at higher temperature. And then on top of that, we saw that in the teeth of forceps — a model surgical instrument — the enzymatic surfactant does not easily go into confined areas and cannot remove the bacterial film from those areas. But with our particle system, we actually could remove the films in those spaces. That's a huge difference," Kong said.
In the second paper, published in the journal Advanced Science, the researchers embedded the microparticles into bandages to dress persistent wounds, another place where biofilms frequently form.
"Chronic wounds affect millions of patients, including about 10.5 million Medicare beneficiaries in the United States, and biofilms are found in 60-80% of chronic wounds," Kong said.
The researchers embedded the microparticles in the bandages beneath a mesh that steadily releases hydrogen peroxide, activating the particles. They called the bandage assembly a "microblasting wound dressing," as it localizes the microbubble generation at the wound site, continually blasting the wound surface with tiny scrubbing bubbles, said postdoctoral researcher Yujin Ahn, the first author of the paper.
Just as with the surgical instruments, the microparticles and the bubbles they generated dislodged complex biofilms on the wound surface. On mouse wounds with antibiotic-resistant films of the kinds seen often in human patients, the microblasting wound dressing greatly reduced the biofilm present and accelerated healing, with reduced inflammation and skin and hair regrowth, Ahn said. It also enabled antibiotics to penetrate the disrupted biofilm, preventing regrowth even at antibiotic doses ten times lower than standard.
"The central lesson from this work is that treatment-resistant wounds can be understood as a biofilm problem," Kong said. "Dense polymicrobial biofilm matrices limit drug penetration and shield bacteria from therapy. By confining self-propelling bubble generators beneath a hydrogen peroxide-releasing mesh, we remove the biofilm barrier, improving antibiotic efficacy while reducing inflammation during wound healing."
Next, the researchers plan to test their microparticle technology on cleaning surgical endoscopes, whose inner hollow tubes make for very difficult cleaning, as well as applying the bandages to chronic wounds in large animals, Ahn said. The researchers also have obtained a patent for the bubble-generating microparticle technology and are working with partners to explore manufacturing at larger scales.
"We think this has many applications, both clinical and industrial. Biofilms form in many places, and this is a technology that can disrupt them mechanically without harsh chemicals or special equipment," Kong said.
The U.S. National Science Foundation, U.S. National Institutes of Health, the Chan Zuckerberg Biohub Chicago and the Korean Ministry of Trade, Industry and Energy supported this work.
