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Reducing Infection in Total Joint Replacements with Drug-Eluting Implants

In This Article

  • A novel drug-eluting biomaterial in implants for substantially reducing the acute infections seen in total joint patients is described utilizing ultra-high molecular weight polyethylene (UHMWPE)
  • Antibiotics can be added to UHMWPE in eccentric rather than spherical arrangements to allow drug clustering and percolation effects that improve drug delivery control in the joint
  • Complete biofilm eradication in joints is documented, as published in Nature Biomedical Engineering, with experimental treatment of rabbit knees infected with the bacteria Staphylococcus aureus and treated with the antibiotic-eluting UHMWPE implant

Joint infection is a serious and disabling potential complication of total joint replacement surgery. As the population ages and stays active longer across the lifespan, total joint replacement (TJR) is increasingly common, because joints are subjected to more years of arthritis, fractures, sports injuries and prolonged stress. For example, according to the Agency for Healthcare Research and Quality, more than 300,000 total hip replacements are performed each year in the United States, and the AAOS reports that the infection rate is approximately 1 in 100.

To eliminate infection and restore comfort, function and quality of life, patients typically undergo months of medical management with antibiotics and often, two surgeries. In the first operation, the surgeon removes the infected implant, cleans the surrounding tissue and implants a temporary drug-eluting spacer of bone cement to stabilize and disinfect the joint for six months. In the second operation, the surgeon removes the spacer and the patient receives a new implant.

Iterative Innovation

Given the significant total joint patient population at risk, the need to prevent or reduce joint infections is urgent. To address this, Orhun Muratoglu, PhD, director of Massachusetts General Hospital’s Harris Orthopaedics Laboratory, Harvard/MIT MD/PhD Student Jeremy Vincentius Suhardi, Ebru Oral, PhD, associate director of biomaterials and colleagues developed a promising new drug-eluting joint implant technology.

A key advance of the new technology is the team’s discovery of how to add antibiotics to ultra-high molecular weight polyethylene (UHMWPE) material. The solution hinges on the polyethylene trait that enables drug clusters that are eccentric, not spherical. This modifies a property known as the percolation threshold, which affects drug delivery control.

“When the aspects are just right and have the correct fractional loading, you get percolation of domains that connects them to each other,” Dr. Muratoglu says. Importantly, percolation enables physicians to sustain drug delivery at the right level and duration to the joint.

Evidence for Advantages of UHMWPE

Experimental data show the new implant technology offers multiple advantages. Among them are:

  • Ability to sustain the deliv­ery of the drug and maintain the necessary mechanical strength to withstand loading stresses patients need in a fully functional joint implant
  • Substantially reduce the acute infections seen in total joint patients, as the team reported in 2017 in the journal Nature Biomedical Engineering: the treatment of rabbit knees infected with the bacteria Staphylococcus aureus with the antibiotic-eluting UHMWPE led to complete biofilm eradication
  • Potentially reducing the need for patients to undergo multiple surgeries
  • Effectiveness against multiple bacterial strains
  • High-concentration of antibiotic delivery. This minimizes the development of resistant bacterial strains by delivering combined antibiotics at the desirable rate to eliminate bacteria and the formation of highly destructive pathogenic biofilms

“The driver for us was to come up with a technology to prevent infection,” Dr. Muratoglu explains. “Now we can have the implant do the sustained elution of the right antibiotic—or combination of antibiotics—at the correct concentration. This is new, and potentially very powerful in terms of reaching the holy grail of one day eliminating infections in total joint replacements.”

His clinical care and co-developer colleague Andrew A. Freiberg, MD, chief of the Center for Hip and Knee Replacement, adds, “This completely novel approach can change the treatment paradigm for patients with an infection around an implant. Now that we have developed new materials that can release antibiotics in a functional joint replacement, patients will someday have a chance at a better infection cure.”

Breaking the Implant-Infection Linkage

The persistent problem with the current generation of total joint replacements is that “artificial material attracts bacteria the body is not adapted to fight effectively,” Dr. Muratoglu says. Artificial material embedded in the body promotes the formation of pathogenic slime-like biofilms on implants.

This is why a seemingly distant input years after successful implant surgery, such as a dental root canal, a scrape or a cut, can endanger an implant patient. It introduces bacteria into the body that eventually seeks and colonizes the implant.

As a result, joint implant patients are at continual risk of infection—the scenario the Mass General Harris Lab team seeks to change. As the drug-eluting UHMWPE hip implant technology moves toward clinical testing and patient use, Dr. Muratoglu is optimistic that a new generation of infection-free, fully functional total joint replacements may be near.

300K
total hip replacements are performed each year in the United States

1
Rate of infection in every 100 THA surgeries

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