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A fully functional drug-eluting joint implant

Nature Biomedical Engineering volume 1, Article number: 0080 (2017) Cite this article

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Abstract

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.

More than one million joint replacements are performed annually in the United States1. Five to ten percent of joint replacements are revised within seven years2, with prosthetic joint infection (PJI) being one of the most common reasons for revision (Fig. KT29 in ref. 3). PJI is an increasing healthcare burden4 with a recurrence rate of 16% (ref. 5) and a mortality rate of 2.5% (ref. 6). End-stage treatments are severely morbid, including multiple revisions, resection arthroplasty, arthrodesis and amputation7.

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Figure 1: Highly eccentric drug-eluting polyethylene.
Figure 2: Highly eccentric drug cluster morphology influences the mechanical and elution properties of the implant material.
Figure 3: Influence of the highly eccentric morphology of modified UHMWPE on its drug elution and mechanical properties.
Figure 4: In vivo evaluation of VPE in joint infection model.
Figure 5: In vitro evaluation of RVPE.
Figure 6: In vivo evaluation of RVPE in a lapine joint infection model.

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Acknowledgements

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.

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Authors and Affiliations

  1. Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

    V. J. Suhardi, D. A. Bichara, O. K. Muratoglu & E. Oral

  2. Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA

    V. J. Suhardi, D. A. Bichara, A. A. Freiberg, H. Rubash, H. Malchau, O. K. Muratoglu & E. Oral

  3. Department of Medical Engineering and Medical Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    V. J. Suhardi, S. J. J. Kwok & S. H. Yun

  4. Wellmann Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

    S. J. J. Kwok & S. H. Yun

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  1. V. J. Suhardi
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Contributions

V.J.S., D.A.B, E.O., O.K.M., H.R., A.A.F., H.M., S.J.J.K. and S.H.Y. designed the experiments. V.J.S., D.A.B. and S.J.J.K. performed the experiments. All authors were involved in the analyses and interpretation of the data. V.J.S., D.A.B., S.J.J.K., E.O. and O.K.M. wrote the paper, with the help of the co-authors.

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Correspondence to E. Oral.

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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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