Novel Drug-eluting Polymer May Improve Treatment of Prosthetic Joint Infection

More than one million joint replacements are performed annually in the U.S. Five to ten percent of these procedures require revision within seven years, and prosthetic joint infection is one of the most common reasons. Moreover, prosthetic joint infection recurs in 16% of cases.

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When a prosthetic joint becomes infected, the standard treatment involves two surgeries. First to remove the implant and insert an antibiotic-eluting bone cement spacer, and, after six to eight weeks (when the infection is cleared), a second to replace the implant. Patients have limited mobility between surgeries, and the spacers made of drug-eluting cement often fracture or become dislocated because they are not designed for continuous load bearing.

In addition, the drug-elution rate from bone cement spacer is low. As a result, antibiotic concentrations often fall below the minimum required to completely eradicate bacteria, which can result in antibiotic resistance.

Now, the Harris Orthopaedic Laboratory at Massachusetts General Hospital has developed an antibiotic-releasing polymer that addresses these shortcomings, explained in a study published in Nature. Implants made from this load-bearing material may someday greatly simplify the treatment of prosthetic joint infection by eliminating the need to place temporary antibiotic-eluting spacers.

David A. Bichara, MD, physician investigator; Andrew Freiberg, MD, chief of the Center for Hip and Knee Replacement; Henrik Malchau, MD, PhD, director emeritus of the Harris Lab; Orhun Muratoglu, PhD; director of the Harris Lab; Ebru Oral, PhD, associate director, Biomaterials, Harris Lab; Harry Rubash, MD, emeritus chief of the Department of Orthopaedic Surgery, and colleagues produced an optimized form of ultrahigh molecular weight polyethylene (UHMWPE), which has a long track record of safety and efficacy when used in joint implants. In the novel polymer, the antibiotic clusters are irregularly shaped instead of spherical. This design is intended to allow the material to release more effective drug doses over more extended periods of time without compromising its strength.

In head-to-head laboratory tests, the modified polymer released vancomycin at a higher concentration, and for longer, than the standard antibiotic-eluting bone cement. Furthermore, the novel material retained the mechanical and wear properties of currently available joint prostheses.

The researchers then tested the new polymer in vivo in animal model knees. They placed osteochondral plugs that contained the polymer imbued with vancomycin, the polymer without vancomycin, or standard bone cement. They then injected the knees with a solution of Staphylococcus aureus. Three weeks later, there was no bacterial growth on joint tissues or implants of the animals that received the polymer with vancomycin, whereas substantial amounts of live bacteria were found in all animals that received bone cement.

In a similar experiment, the researchers inserted titanium rods covered by S. aureus biofilms, which are notoriously resistant to antibiotics, into rabbit tibia. This time, the animals had plugs implanted that contained the polymer imbued with both rifampin and vancomycin, the polymer without antibiotics, or standard bone cement. Several days after surgery, the infected knees in animals that received the antibiotic-eluting polymer were less swollen, retracted and passive than those in the two comparison groups. At autopsy, no mechanical failure was observed in any implants.

For the next step, researchers recommend conducting a clinical trial of the antibiotic-eluting polymer as a joint implant. It has the potential, they say, to eliminate the use of temporary antibiotic-eluting spacers, thereby simplifying the standard two-stage treatment for prosthetic joint infection into a single surgery.

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