Editors' ChoiceTissue Engineering

Eccentric implants stand alone

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Science Translational Medicine  05 Jul 2017:
Vol. 9, Issue 397, eaan8199
DOI: 10.1126/scitranslmed.aan8199

Abstract

Controlling antibiotic drug clustering in replacement joint material provides a single-step strategy to clear infection while maintaining the mechanical strength needed for load bearing.

Logic is a cornerstone of science, but many discoveries occur by accident. To name a few: pacemakers, microwaves, and don’t forget Play-Doh—first created to clean wallpaper! A touch of eccentricity can ensure that these moments of opportunity are capitalized on. In their recent article, Suhardi et al. exploit a different type of eccentricity to design implantable joints that could enable safer, faster intervention during joint implant infection.

Prosthetic joint infection is one of the most common complications of joint replacement. The current two-step procedure for addressing infections involves removing the infected implant, placing temporary bone cement loaded with antibiotics to clear the infection, and then implanting a new prosthetic joint after 1 to 2 months. Existing bone cements exhibit large spherical drug clusters aimed at eluting drug over this 2-month interval. Unfortunately, these high concentrations can be toxic for some antibiotics and diminish mechanical properties, which severely limit patient mobility during the first phase.

Here, the authors forced an eccentric drug cluster arrangement of small, nonspherical clusters throughout ultra-high molecular weight polyethylene (UHMWPE). Polymer processing was used to promote drug dispersion, with optimal elution achieved at 7% drug loading by weight, compared with 40 to 60% required in existing materials. UHMWPE loaded with antibiotics provided longer term release compared with clinical antibiotic-releasing bone cements and maintained clinically acceptable mechanical properties owing to the lower proportion of drug in the UHMWPE. Importantly, this approach eliminated the need for bone cement, resulting in a one-step corrective surgery instead of two. After one year incubation in buffer, drug-loaded UHMWPE still prevented Staphylococcus aureus growth in vitro. Implants with eccentric drug dispersions eradicated bacteria when implanted in the knee joint in rabbits before infection or when implanted near titanium plugs precoated with biofilms. All drug-loaded UHMPWE-treated animals survived, whereas all animals in groups treated with common drug-loaded bone cement formulations succumbed. Greater than 95% of the biofilm was eradicated and no mechanical failures were observed with the eccentric implants, nor were there systemic impacts on kidney and liver function.

Although the authors propose design criteria for human trials, some important questions remain unanswered. Will these implants maintain the minimum drug levels needed to avoid antibiotic resistance—and for long enough to clear infection? Existing antibiotic-releasing materials face both of these challenges. Nevertheless, the work described here could help patients to their feet faster by achieving durable drug release without sacrificing mechanical properties.

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