Abstract
Introduction
UHMWPE particle-induced osteolysis is one of the major causes of arthroplasty revisions. Recent in vitro findings have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis (Bladed C. L. et al, JBMR B 2012 and 2013). This is of significant importance since VE-stabilized cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear debris. In this study we hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE.
Methodology
Study groups were the following: 1). Radiation cross-linked VE-UHMWPE (0.8% by weight) diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Sham controls. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions (Oak Park, IL) for particle generation. After IACUC approval, C57BL/6 mice (n=12 for each group) received equal amount of particulate debris (3mg) overlying the calvarium and were euthanized after 10 days. Micro-CT scans: High resolution micro-CT scans were performed using a set voltage of 70 kV and current of 70 µA. Topographical Grading Scale: Each calvarial bone was blindly scored using the following scale: 0=No osteolysis, defined as intact bone; 1=Minimal osteolysis, affecting 1/3 or less of the bone area; 2=Moderate osteolysis, affecting at least 2/3 of the bone area; 3=Severe osteolysis, defined as completely osteolytic bone. Histology: H&E and TRAP staining was done on tissue to confirm micro-CT findings and quantify osteoclasts. Statistical Analysis: Inter-rater analysis was done using Cohen's kappa analysis. An inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. P-value<0.05 was considered statistically significant.
Results
More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 µm in mean particle size. There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. Micro-CT findings were confirmed histologically (Fig. 1). A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p=0.002) but no difference in osteoclast counts (p=0.293).
Discussion and Conclusion
This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Arthroplasty procedures using VE-UHMWPE might be less susceptible to peri-prosthetic loosening caused by wear debris.
