Abstract
We have demonstrated that erythromycin (EM) inhibits wear debris-induced macrophage activation and osteo-clastogenesis (both in vitro and in vivo) through targeting NF-κB signalling. Our clinical trial further verified that oral EM can be efficiently delivered to periprosthetic tissue and improve local inflammation. The purpose of this study was to assess the efficacy of periprosthetic EM delivery in a rat osteolysis model.
The PA coated titanium (Ti) pin (Stryker) was loaded with EM (8 μl = 2.8 mg/pin). Drug release assay showed around 25% of loaded EM was remained in the PA layer 24 hours after loading. Rats were divided into three groups:
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saline control (n=5);
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UHMWPE particle injection (n=7), and
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UHMWPE particle injection with EM treatment (n=7).
Uncoated Ti pins were pressfit inserted into right tibia following the injection 200 μl of either UHMWPE particles (5 mg/ml) or saline (control). The revision surgeries were performed 6 weeks after the first surgery. The previous implanted pins were replaced with new Ti pins either with or without EM coating. Rats were then sacrificed one month after “revision surgery”, and the knee joint samples were collected for μCT and histology analysis.
μCT analysis showed that the value of bone volume (bv/tv) in the group treated with EM (0.26 ± 0.07) was significantly higher than the group untreated (0.14 ± 0.04), while there was no significant difference between EM treated group and the saline control group (0.15 ± 0.11). The parameters of cancellous bone structure all pointed a trend of better structure in EM treated group than other two groups. However, this difference did not reach statistical significance. Histology analysis (H& E staining) demonstrated that in the saline control the tibia retained a smooth endocortical surface with a prominent periprosthetic membrane. In the EM-treated group, endocortical erosion was reduced and the peri-prosthetic tissue appeared thinner than uncoated pins.
The overall cellularity of periprosthetic membranes from the EM-treated group was decreased compared to the untreated group. Analysis of membrane thickness revealed a significantly thinner membrane in EM-treated group compared with untreated group and saline control (p< 0.05).
The results of this study seem to indicate that an EM coated Ti pin provided a sufficient drug source to effectively treat wear debris-induced periprosthetic inflammation and osteolysis.
Correspondence should be addressed to Diane Przepiorski at ISTA, PO Box 6564, Auburn, CA 95604, USA. Phone: +1 916-454-9884; Fax: +1 916-454-9882; E-mail: ista@pacbell.net
