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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