Advancing Joint Infection Treatment: Long-Term Animal Implantation of Submicron Gentamicin-Loaded UHMWPE

Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty, often necessitating two-stage revision surgery with antibiotic-loaded bone cement (ALBC) spacers, which cannot maintain therapeutic local antibiotic concentrations over time. This study evaluated the long-term stability, antimicrobial efficacy, and biocompatibility of an alternative material, submicron gentamicin sulfate-loaded ultrahigh molecular weight polyethylene (SM-GS/UHMWPE), in vitro and in vivo by using a subcutaneous rat model. SM-GS/UHMWPE implants containing 6 wt% and 10 wt% gentamicin sulfate (GS) were fabricated and tested in vitro and simultaneously in vivo by subcutaneous implantation in rats for 4, 8, and 26 weeks. Gentamicin stability was assessed using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS/MS). Antimicrobial efficacy against Staphylococcus aureus was determined via bacterial culture assays. Mechanical integrity was evaluated using tensile testing in vitro. Systemic toxicity was assessed through liver and kidney function markers, and histological analysis of kidney and skin tissues was performed. NMR and LC-MS/MS confirmed that gentamicin remained chemically stable over 26 weeks in vivo and in vitro. Antimicrobial testing showed sustained bacterial inhibition, with implants containing 10% GS achieving a 3.5-log reduction in bacterial counts for 6 months. Mechanical testing demonstrated minimal changes in tensile properties over time. Serum biochemical markers remained within normal ranges, and histological evaluation showed no significant inflammation or tissue damage. Gentamicin elution profiles indicated sustained release, maintaining intraarticular levels above 100 times the minimum inhibitory concentration (MIC) of S. aureus for 6 months. SM-GS/UHMWPE implants demonstrated prolonged antibiotic release while maintaining mechanical integrity, antimicrobial efficacy, and biocompatibility. These findings support the potential use of SM-GS/UHMWPE as a next-generation antibiotic-eluting spacer for PJI treatment, offering an alternative to ALBC for sustained drug release and reduced systemic toxicity risks.