Maths, medicine and microbiology : preventing periprosthetic infection

Introduction: Periprosthetic implant infection develops weeks to months after orthopaedic surgery. Infections caused by bacterial biofilms are difficult to treat, with revision surgery often necessary. This delays recovery and prolongs hospital stays, meaning new solutions for prevention are critical. Antibiotic-eluting biodegradable polymeric coatings are a potential solution, but they require optimisation. This study characterised the long-term in vitro release profiles and antimicrobial efficacy of rifampicin and poly(lactic-co-glycolic acid) (PLGA) coatings.
Methods: Three ratios of PLGA:rifampicin (50:50, 60:40, and 75:25) were dip-coated onto stainless steel samples and submerged in PBS (37°C) for 16 weeks. Elution was measured by UV-vis spectrophotometry. A subset of 50:50 coated samples were removed from PBS at selected elution time points and incubated in Staphylococcus aureus suspension at 37°C for 24h. Adhered bacteria were removed by sonication and enumerated by standard microbiological methods.
Results: All coatings demonstrated distinct elution behaviour (P<0.05). The 50:50 and 60:40 coatings displayed a ‘burst’ release within the first 24h, while the 75:25 had very little release before 28 days, after which a slow release was observed. Release from the 50:50 coating was >99% complete by 7 days while 60:40 and 75:25 continued to release up to at least 16 weeks. Preliminary analysis suggests that the release is dominated by diffusion, although other mechanisms may also have an influence. Bacterial inhibition >99% was maintained up to 12 weeks by the 50:50 coating, demonstrating bacterial attachment is significantly inhibited (P<0.05) by surface rifampicin even when elution has mostly completed.
Conclusions: The developed coatings provide a means of tuning drug release kinetics, which with further optimisation, may provide protection against infection that can be tailored to particular clinical scenarios. This can be informed by in silico modelling work which is now underway, opening up future opportunities for better prevention of infections in orthopaedic implants.