Despite advances in orthopaedic materials, the development of drug-eluting bone and joint implants that can sustain the delivery of the drug and maintain the necessary mechanical strength to withstand loading has remained elusive. Here, we demonstrate that modifying the eccentricity of drug clusters and the percolation threshold in ultra-high molecular weight polyethylene (UHMWPE) results in maximized drug elution and the retention of mechanical strength. The optimized UHMWPE eluted antibiotic at a higher concentration for longer than the clinical gold standard antibiotic-eluting bone cement, while retaining the mechanical and wear properties of clinically used UHMWPE joint prostheses. Treatment of lapine knees infected with Staphylococcus aureus with the antibiotic-eluting UHMWPE led to complete bacterial eradication and the absence of detectable systemic effects. We argue that the antibiotic-eluting UHMWPE joint implant is a promising candidate for clinical trials.
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We are grateful to G. Wojkiewicz and B. Tricot from the Center for Systems Biology, Massachusetts General Hospital (MGH) for their assistance with the bioluminescence imaging. This work was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network (NNN), which is supported by the National Science Foundation (NSF) under NSF award no. ECS-0335765. The CNS is part of Harvard University. This study was supported in part by the Harris Orthopedics Lab Sundry Fund, MGH Orthopedics Departmental Fund, US National Institutes of Health grants P01-HL120839 and P41-EB015903.
The authors declare no competing financial interests.
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Suhardi, V., Bichara, D., Kwok, S. et al. A fully functional drug-eluting joint implant. Nat Biomed Eng 1, 0080 (2017). https://doi.org/10.1038/s41551-017-0080
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