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Drug eluting prosthetic joints through drug cluster morphology control

Author(s)
Suhardi, Vincentius Jeremy
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Harvard--MIT Program in Health Sciences and Technology.
Advisor
Ebru Oral.
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MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582
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Abstract
More than one million joint replacements are performed in the USA annually. However, around 10 % of patients require revision surgery within 10 years with prosthetic joint infections (PJI) as a common reason. PJI has a recurrence rate of 16 %, a mortality rate of 2.5 %, and end-stage treatments involving arthrodesis and amputation. Most drug eluting polymers that were in development to address this problem failed due to toxic degradation products, insufficient drug release, and insufficient mechanical strength. The gold standard of treatment uses antibiotic eluting bone cement which has a mechanical failure rate of 26-60 % within 49-54 months if used under load bearing conditions. Therefore, despite advances in orthopedic materials, development of drug-eluting devices with effective, sustained delivery with the necessary mechanical strength for a fully load bearing joint implant has been elusive. Here, we report the synthesis and application of a drug eluting, fully load bearing, and articulating joint prosthesis that has superior mechanical strength and drug elution profile compared to the clinical gold standard, antibiotic eluting bone cement. We modified the eccentricity of drug clusters and percolation threshold in the polymeric matrix of Ultra-High Molecular Weight Polyethylene (UHMWPE), which resulted in maximized drug elution and mechanical strength retention. The optimized antibiotic eluting UHMWPE elutes antibiotic at a higher concentration for a longer period of time than antibiotic eluting bone cement while retaining the mechanical and wear properties of clinically used UHMWPE joint prosthesis. After drug elution, the empty drug clusters in the polymer were filled with biological lubricants during articulation, which through a combination of weeping and elastohydrodynamic lubrication, reduced the overall wear rate of the UHMWPE. Treatment of Staphylococcus aureus infected lapine knee with the antibiotic eluting UHMWPE showed complete bacterial eradication without any detectable systemic side effect. Taken together, our study showed that the drug-eluting UHMWPE joint implants in this study are promising candidates for further clinical trial and as the next generation prosthetic joints.
Description
Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2017.
 
Cataloged from PDF version of thesis.
 
Includes bibliographical references (pages 299-330).
 
Date issued
2017
URI
http://hdl.handle.net/1721.1/111323
Department
Harvard University--MIT Division of Health Sciences and Technology
Publisher
Massachusetts Institute of Technology
Keywords
Harvard--MIT Program in Health Sciences and Technology.

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