A Next-Generation Approach for Managing Periprosthetic Joint Infection in Total Joint Arthroplasty
In This Article
- Total knee arthroplasty is associated with periprosthetic infections in 2% of cases and heightened mortality rates at five-, 10-, and 15-year follow-up
- A solution under development at Massachusetts General Hospital's Harris Lab incorporates gentamicin sulfate directly into ultra-high-molecular-weight polyethylene for use in joint replacements
- Orhun Muratoglu, PhD, director of the Harris Orthopaedics Lab, expects to receive FDA clearance for the technology platform by mid-2026
Researchers at the Harris Orthopaedics Laboratory at Massachusetts General Hospital, led by director Orhun K. Muratoglu, PhD, and deputy director Ebru Oral, PhD, are developing an ultra-high-molecular-weight polyethylene (UHMWPE) temporary spacer capable of delivering localized gentamycin sulfate. Their goal is to improve infection control during two-stage revision arthroplasty while maintaining joint function and enhancing patient mobility throughout the interim treatment period.
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Periprosthetic joint infection (PJI), which occurs in approximately 2% of total knee arthroplasties (TKAs), is one of the most difficult complications encountered in arthroplasty. A 2023 study reported a 2% infection rate following primary TKA, while a 2025 registry analysis found mortality rates of 16%, 34%, and 53% at five-, 10-, and 15-year follow-up, respectively.
Two-stage revision arthroplasty remains the accepted standard for chronic PJI yet presents significant clinical limitations. Removal of well-fixed implants is often technically demanding. Temporary poly(methyl methacrylate), or PMMA, spacers lack stable articulation and are prone to mechanical failure. Antibiotic release from cement is inconsistent and often insufficient, requiring prolonged systemic antibiotics that expose patients to risks such as nephrotoxicity and hepatotoxicity. Reinfection remains common, with reported rates of 23% at one year and 62% at five years; meanwhile, mortality at three years approaches 11%.
These challenges motivated Drs. Muratoglu and Oral, in collaboration with Mass General Brigham colleagues Jeremy Suhardi, MD, PhD, Harry E. Rubash, MD, Andrew A. Freiberg, MD, and Henrik Malchau, MD, PhD, to develop a load-bearing, antibiotic-eluting UHMWPE spacer as a functional alternative to PMMA-based constructs.
Embedding Gentamycin Directly Into UHMWPE
UHMWPE is well-established as a durable, wear-resistant bearing material in joint arthroplasty. Unlike PMMA, UHMWPE offers excellent mechanical strength, predictable wear characteristics, and the ability to articulate safely under physiologic loading. Embedding gentamycin directly into UHMWPE enables sustained, high, local antibiotic concentrations at the infection site while minimizing systemic toxicity. It also enhances patient mobility during the spacer phase.
Early efforts to create an antibiotic-eluting UHMWPE material revealed challenges when conventional gentamycin sulfate was blended directly with polyethylene powder, as larger antibiotic agglomerates interfered with polymer consolidation and weakened the mechanical properties of the final material. Mehmet Asik, PhD, then a postdoctoral fellow, proposed a breakthrough: reducing the size of gentamycin particles from ~250 microns to the submicron range and embedding them within the natural porosity of polyethylene.
"The idea was to hide the particles within the polyethylene matrix so they wouldn't interfere with consolidation or weaken the material," Dr. Muratoglu says.
This insight allowed the team to create a formulation in which approximately 8% gentamycin sulfate is integrated throughout the polymer matrix while preserving more than 90% of baseline UHMWPE mechanical strength. The material also demonstrated excellent wear resistance and sustained, therapeutic levels of antibiotic release substantially greater than that achieved with PMMA.
The development and characterization of this antibiotic-eluting UHMWPE, including evaluations of mechanical performance, wear behavior, and elution kinetics, were published in The Journal of Bone & Joint Surgery. This peer-reviewed publication provided foundational validation that antibiotics can be incorporated into UHMWPE without compromising durability, establishing the feasibility of a load-bearing antibiotic-eluting spacer for staged revision arthroplasty.
Progressing Toward Clinical Application
The first planned clinical application of this technology is a UHMWPE tibial-femoral temporary spacer for two-stage revision TKA. Because both components are made of UHMWPE, articulation more closely resembles that of a definitive implant, weight-bearing is supported more reliably, and mechanical complications such as fracture or dislocation are less likely than with PMMA spacers. The spacer is designed to remain in place for up to six months before reimplantation and intended to deliver high local gentamycin concentrations without the systemic toxicity associated with prolonged intravenous antibiotics.
Under the leadership of Drs. Muratoglu and Oral, the project is progressing toward clinical translation. Preclinical testing is ongoing, FDA submission for a Class II device took place in January 2026, clearance is anticipated in mid-2026, and first clinical use is expected in late 2026. The researchers also envision extensions of this technology to hip and shoulder PJI spacers.
"If clinical results mirror preclinical performance, this technology has the potential to improve infection control during the spacer phase, reduce the need for systemic antibiotics, decrease spacer-related mechanical complications, enhance interim mobility and patient comfort, and ultimately reduce reinfection rates in staged revision procedures," Dr. Muratoglu notes. Importantly, he adds, the device integrates directly into existing surgical workflows and requires no modifications to operative technique.