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

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.

Figure 1

Endotoxin reduction and particle yield as a function of time. Log reduction of endotoxin content and percentage yield (total mass) in MoM wear particles was determied over time after treatment with 0.05 M NaOH.

Figure 2

0.05 M NaOH-treatment does not alter physical characteristics of MoM Wear Particles. TEM analysis was performed to assess MoM wear particles: (A) prior to treatment at 10X and 20X magnification; (B) after 0.05 M NaOH treatment for 24 hours at 10X and 20X magnification.

Figure 3

0.05 M NaOH treatment for 24 hours does not alter physical characteristics of MoM Wear Particles. (A) Primary particle size for MoM wear particles was measured by TEM before and after 24 hour treatment with 0.05 M NaOH and plotted as distribution by number. (B) Primary particle size for MoM wear particles was measured by TEM before and after 24 hour treatment with 0.05 M NaOH and plotted as distribution by volume.