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A novel presurgical vaccine strategy may prevent dangerous periprosthetic joint infections (PJI) in patients receiving hip, knee, and other joint replacements.

A multidisciplinary team, led by Alexander Tatara, MD, PhD, from UT Southwestern and David Mooney, PhD, from Harvard University, created an injectable scaffold designed to stimulate the immune system.

The scaffold acts as a potent immunotherapy against bacterial infections of the bones and joints, including those caused by methicillin-resistant Staphylococcus aureus (MRSA).  S. aureus is the leading cause of PJIs in orthopaedic devices.

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In the team’s study, published in Proceedings of the National Academy of Sciences, the scaffold-based vaccine triggered a robust immune reaction in a mouse model, reducing bacteria levels over 100 times more than conventional soluble vaccine formulations.

Preventing Biofilm Formation

“In the U.S. alone, orthopaedic surgeons perform more than a million knee and hip replacements each year, and 2% to 3% of those implanted devices become infected,” Dr. Tatara said.

“Those infections are the result of bacteria that attach to the surface of the replacement joint, producing a sticky, layered substance called biofilm that is resistant to most antibiotics.”

Because biofilms resist traditional treatments – and artificial joints made of metal or plastic lack blood flow to deliver immune cells – post-surgical infections can be difficult to control and even life-threatening, particularly for patients with weakened immune systems. Researchers believe a scaffold vaccination given in advance of surgery could prime the body’s natural immune defense and prevent the formation of biofilm.

“Orthopaedic hardware infections often require multiple additional surgeries and long courses of antibiotics to treat, including lifelong oral antibiotics in some cases,” Dr. Tatara said.

“Recovery can take up to a year, and successful treatment depends heavily on early intervention. If we can bring this technology from the laboratory to the patient, we can better protect those who benefit from orthopedic implants.”

Stimulating an Immune Response

Scaffold vaccinations work by creating a 3D framework made from porous, biocompatible materials such as cryogels or silica rods. These biomaterials are loaded with bacterial antigens to draw in and activate immune cells, stimulating the body’s natural response. As the immune response builds, the scaffold slowly degrades.

The study found this localized, sustained approach to be far more effective than liquid vaccines, which disperse rapidly.

“With the rise in antibiotic resistance, treatments that don’t rely on traditional antibiotics are more important than ever,” Dr. Tatara said.

“The scaffold vaccine works like a temporary construction platform, concentrating and training the immune system to recognize bacteria such as Staphylococcus aureus. It may allow us to ‘front-load’ immune protection before surgery, especially for patients at higher risk of infection.”

This study was funded by grants from the National Institutes of Health, Harvard Catalyst|The Harvard Clinical and Translational Science Center, the Wyss Institute, Harvard University, and the National Cancer Institute.

Source

Tatara AM, Lightbown S, Kang S, et al. Scaffold vaccination for prevention of orthopedic device infection. Proc Natl Acad Sci U S A. 2025 Nov 11;122(45):e2409562122. doi: 10.1073/pnas.2409562122. Epub 2025 Nov 3.