Methods for Sterilizing Clinically Relevant Wear Particles Isolated from Metal-on-Metal Hip Implants

Ernest S Fung,Kenneth M Unice,Brent L Finley,Michael Kovochich,Dennis J Paustenbach

doi:10.1038/s41598-017-18239-4

Ernest S Fung, Kenneth M Unice + Show 3 more

Open Access

https://doi.org/10.1038/s41598-017-18239-4

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Abstract

Engineered or incidental particles may contain endotoxin from contaminated environments associated with generation, production, or handling activities. Endotoxins are ubiquitous contaminants that may yield false positive responses in immunological assays if present. The purpose of this study was to develop a sterilization method for removal of endotoxin from clinically relevant wear particles isolated from metal-on-metal (MoM) hip implant lubricant. In this case, the goal of particle sterilization was to sufficiently reduce endotoxin levels to acceptable levels for sensitive biological assays while retaining the physical and chemical characteristics of the original particles. Optimization of treatment with 0.05 NaOH in 50% ethanol successfully achieved a 5-log (>99.999%) reduction of endotoxin content while retaining the size and chemistry of MoM hip implant wear particles. Using the optimized method, the concentration of endotoxin was reduced from 161,000 to 1.19 EU/mL. As particle types can vary, sterilization strategies will also differ to optimize endotoxin removal while retaining key particle characteristics. To our knowledge, this study represents the first published sterilization method for clinically relevant MoM hip implant wear particles isolated from serum-rich lubricant.

Highlights

There is an extensive amount of ongoing research focused on the potential contribution of metal particles and ions released from metal-on-metal (MoM) hip implants to observed biological responses[1,2]
The goal of “depyrogenation” is to reduce endotoxin content to levels that do not elicit an inflammatory response. The purpose of this communication, is to describe an optimized sterilization method for effective endotoxin removal from clinically relevant MoM wear particles isolated from serum-rich lubricant
Initial testing showed that 0.05 M sodium hydroxide treatment efficiently reduced the endotoxin content without altering the physical and chemical characteristics of the wear debris particles

Summary

Introduction

There is an extensive amount of ongoing research focused on the potential contribution of metal particles and ions released from metal-on-metal (MoM) hip implants to observed biological responses[1,2]. Many previous toxicological studies have utilized particles with physical and chemical characteristics that differ from particles released from MoM implants under normal wear conditions[1,2]. Numerous studies have evaluated the biological responses (in vitro and in vivo) induced by metal particles collected from hip simulators that were operated in an aqueous solution with no protein lubricant[3,4,5,6]. The main limitation of this study design is that the wear particles that are generated in water display significant chemical differences (more cobalt) compared to particles that are generated under physiologically relevant conditions with serum-containing lubricant solution[1,2]

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