Friday, April 10, 2020

Potential new treatment for joint infections

A new therapy could help overcome joint infections in horses. Researchers at North Carolina State University developed a platelet-rich plasma (PRP) lysate that, when teamed with antibiotics, can eradicate bacterial biofilms common in joint infections. The work, which received funding from the Morris Animal Foundation, has been published in the Journal of Orthopaedic Research.

"This could really provide a more effective way of clearing a joint infection quickly so that the horse does not suffer long-term consequences of joint damage," said Dr. Lauren Schnabel, Associate Professor of Equine Orthopaedic Surgery at North Carolina State University, a primary investigator of the study. "For any horse's well-being, it's important to make them as comfortable as possible, as quickly as possible to avoid laminitis and other complications."

Penetrating wounds of the joint in horses are potentially life-threatening. Joint infection is a challenge to overcome, frequently requiring repeated flushing and prolonged antibiotic treatment. Even if the infection is cleared, it may leave permanent damage, resulting in degenerative joint disease.

Successful treatment is hindered by the tendency for some bacteria to form biofilms in the joint. A biofilm is a sticky, slimy shield that forms around bacteria. It protects them from the body’s immune cells. The bacteria in the biofilm tend to be metabolically inactive, which makes them more resistant to antibiotics.

Platelets are a rich source of protein growth factors that promote healing. Platelet Rich Plasma (PRP) is made by processing a sample of the patient’s own blood to increase the number of platelets and growth factors it contains. PRP has found various uses in regenerative medicine, including the treatment of tendon and ligament injuries.

To create their PRP lysate, the research team took blood from their small herd of horses and isolated the platelets. Then they packed 50 times the number of platelets that would be found in an equal amount of blood into their product. This is over 10x the concentration of platelets typically found in conventional PRP. They felt that this super-concentrated product would be more effective at stopping infections.

The researchers lysed the platelets to release antimicrobial peptides - proteins that attack bacteria. They separated out the antimicrobial peptides and then, after testing them against common bacteria, all the horses' peptides were pooled together for one lysate product. 

Then, samples of synovial fluid were seeded with bacteria in the laboratory to produce bioflilms.
The researchers tested three methods to attack the biofilms; antibiotics alone, lysate alone and a combination of antibiotics and lysate.

They found that antibiotics alone were completely ineffective. The lysate alone significantly decreased the bacterial load. The antibiotic and lysate combination, however, completely eradicated the biofilms and bacteria.

Dr. Schnabel added that her team has used this experimental therapy on horses with great results. Because the process to create the lysate is both complicated and expensive, her team is trying to find a way to produce it more efficiently. They also are trying to identify the exact peptides responsible for the antibacterial properties, so they can be synthesized and production scaled up to reach the greatest number of horses.

If successful, this approach also has the potential to help other species, including humans. For example, biofilm formation and infection are a significant problem for people with metal implants, such as those used in joint replacement surgeries.

Dr. Jessica Gilbertie, first author on this publication and former Morris Animal Foundation Fellowship trainee under the mentorship of Dr. Schnabel, is working on making PRP lysate from other species, including dogs, because they also can suffer from biofilm formations related to surgical procedures.

For more details, see:

Platelet‐rich plasma lysate displays antibiofilm properties and restores antimicrobial activity against synovial fluid biofilms in vitro
Jessica M. Gilbertie, Thomas P. Schaer, Alicia G. Schubert, Megan E. Jacob, Stefano Menegatti, R. Ashton Lavoie, Lauren V. Schnabel
Journal of Orthopaedic Research (2020)

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