Breaking through the bacterial barrier in chronic therapy-resistant wounds

Researchers from the UNC School of Medicine’s Department of Microbiology and Immunology and the UNC-NC Collaborative Department of Biomedical Engineering have developed a new strategy to improve drug delivery to chronic wound infections.

A chronic wound is an open ulcer or tissue injury that does not heal properly. These types of wounds are notoriously difficult to treat because of bacterial infections such as: Staphylococcus aureusagain Staphylococcus aureus.In addition, bacterial infections that are highly resistant to antibiotics, such as methicillin-resistant bacteria Staphylococcus aureus (MRSA) is one of the leading causes of life-threatening infections in hospitalized patients.

To protect our immune system and other threats, Staphylococcus aureus They can band together to create a smooth, slimy force field around themselves — a biofilm. The biofilm barrier is so thick that neither immune cells nor antibiotics can penetrate and neutralize harmful bacteria.

Researchers from the UNC School of Medicine and the UNC-NC Joint Department of Biomedical Engineering have developed a novel method that combines palmitoleic acid, gentamicin, and noninvasive ultrasound to improve drug delivery to infected chronic wounds. Staphylococcus aureus.

Dr. Sarah Lowkonlon

Researchers used a new strategy to successfully reduce the challenging MRSA infection in diabetic mouse wounds by 94%. We were able to completely disinfect the wounds of some mice, and the remaining mice had a greatly reduced bacterial burden. their result is cell chemical biology.

“When chronic wounds are not completely cleared of bacteria, patients are at increased risk of recurring infections or developing secondary infections,” says Sarah, lead author and associate research professor in the Department of Microbiology. Dr. Lowkonron said: immunology. “This therapeutic strategy has the potential to improve outcomes and reduce recurrence of chronic wound infections in patients. We are excited about the potential clinical application of this and are currently exploring it.” is.”

Biofilms act as physical barriers to many classes of antibiotics. Dr. Virginie Papadopoulou, research associate professor at the UNC-NCSU Joint School of Biomedical Engineering, wanted to know if non-invasive cavitation-enhanced ultrasound could induce enough agitation to create spaces within biofilms to facilitate drug delivery. I was thinking.

A droplet that can be activated by ultrasound, called a phase-change contrast agent (PCCA), is applied topically to the wound. When the ultrasonic transducer is focused on the wound and turned on, the liquid within the droplet expands and transforms into fine gas-filled microbubbles that move rapidly.

Vibration of these microbubbles agitates the biofilm, mechanically disrupting the biofilm as well as increasing fluid flow. Ultimately, the combination of biofilm disruption and increased penetration of drugs across biofilms allowed drugs to enter and kill bacterial biofilms with very high efficiency.

“Microbubbles and phase-change contrast agents act as local amplifiers of ultrasound energy, so they can be precisely targeted to wounds and areas of the body to achieve therapeutic results not possible with standard ultrasound. ‘ said Dayton, William R. Kennan Jr. Distinguished Professor. Head of the UNC-NCSU Joint Department of Biomedical Engineering. “We hope to use similar techniques to locally administer chemotherapy to stubborn tumors or to deliver new genetic material to damaged cells.”

Dr. Paul Dayton

When bacterial cells become trapped within biofilms, they have little access to nutrients and oxygen. To conserve resources and energy, they go dormant or sleepy. Bacteria in this state are known as persistent cells and are highly resistant to antibiotics.

The researchers chose gentamicin, a topical antibiotic that is generally ineffective. Staphylococcus aureus It is caused by widespread antibiotic resistance and reduced activity against persister cells. The researchers also introduced a new antibiotic adjuvant, palmitoleic acid, into the model.

Palmitoleic acid, an unsaturated fatty acid, is a natural product of the human body and has strong antibacterial properties. Fatty acids are embedded in the membrane of bacterial cells, and the authors found that they facilitate the entry of antibiotics into the cell membrane. Staphylococcus aureus It can kill persister cells and reverse antibiotic resistance.

Overall, the research team believes that new topical, non-commercial treatments may provide scientists and physicians with more tools to combat antibiotic resistance and reduce the severe side effects of taking oral antibiotics. We are passionate about invasive approaches.

“Systemic antibiotics, such as those administered orally or intravenously, work very well, but often come with great risks, such as toxicity and destruction of the gut microbiome. C. difficile It’s an infection,” said Lowe-Conlon. “Using this system, topical drugs can work effectively and can be applied to the site of infection at very high concentrations without the risks associated with systemic delivery.”

Media contact: Kendall DanielsCommunications Specialist, UNC Health | UNC School of Medicine

About UNC School of Medicine

The UNC School of Medicine (SOM) is the state’s largest medical school, graduating over 180 new doctors each year. Consistently ranked among the top medical schools in the United States, he includes five colleges among Overall Primary Care by US News & World Report, and 6th For research between public universities. More than half of the school’s 1,700 faculty members have served as Principal Investigators for the Active Research Award in 2021. Two UNC SOM faculty members have been awarded Nobel Prizes.

About Joint Department of Biomedical Engineering

The Integrative Faculty is ranked among the top 10 biomedical engineering programs in the United States by the Blue Ridge Institute of Medicine and among the top 20 biomedical engineering programs in the world by the Shanghai Academic Ranking of World Universities.d is among the top five institutions for total Bachelor’s degrees awarded in Biomedical Engineering (ASEE).

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