Antibiotic‐Loaded Ultrahigh Molecular Weight Polyethylenes

Abstract

The occurrence of periprosthetic joint infections (PJI) after total joint replacement constitutes a great burden for the patients and the healthcare system. Antibiotic‐loaded polymethylmethacrylate (PMMA) bone cement is often used in temporary spacers during antibiotic treatment. PMMA is not a load‐bearing solution and needs to be replaced by a functional implant. Elution from the ultra‐high molecular weight polyethylene (UHMWPE) bearing surface for drug delivery can combine functionality with the release of clinically relevant doses of antibiotics. In this study, the feasibility of incorporating a range of antibiotics into UHMWPE is investigated. Drug stability is assessed by thermo‐gravimetric analysis and nuclear magnetic resonance spectroscopy. Drug‐loaded UHMWPEs are prepared by compression molding, using eight antibiotics at different loading. The predicted intra‐articular concentrations of drugs eluted from UHMWPE are above minimum inhibitory concentration for at least three weeks against Staphylococci, which are the major causative bacteria for PJI. The antibacterial efficacy is confirmed for samples covering 2% of a representative knee implant in vitro over 72 hours, showing that a small fraction of the implant surface loaded with antibiotics might be sufficient against Staphylococci.This article is protected by copyright. All rights reserved

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms

“…Based on the antibiotic susceptibility data from the three different infection models, a high initial dosing of antibiotics (>100 × MIC) is required during the early stages of infection that should be sustained for a prolonged period irrespective of the susceptibility profiles of the bacterial strain. Antibiotic-loaded implant materials that have been developed to locally release high antibiotic concentrations in a sustained manner could be best suited for this application [60][61][62]. For inherently resistant infections, it is advisable to use stronger tools such as the synergistic use of antibiotic and non-antibiotic compounds to enhance the antibacterial activity as early as possible to achieve effective eradication [36,63,64].…”

Irradiation Behavior of Analgesic and Nonsteroidal Anti-Inflammatory Drug-Loaded UHMWPE for Joint Replacement

“…10−15 Leveraging the UHMWPE component in total joint replacement as a delivery device has recently emerged as a potential avenue of investigation. 16,17 In previous studies, it was shown that UHMWPE can be loaded with analgesics to treat postoperative pain and provide prophylaxis against periprosthetic joint infection (PJI). 18−20 Specifically, bupivacaine-loaded UHMWPE implants could release clinically relevant drug doses for pain management in the immediate postoperative period.…”

“…Local drug delivery and delivery systems for nonopioid analgesics and NSAIDs may enhance their benefits by increasing the bioavailability of the drugs at the targeted site while decreasing systemic exposure. − Leveraging the UHMWPE component in total joint replacement as a delivery device has recently emerged as a potential avenue of investigation. , In previous studies, it was shown that UHMWPE can be loaded with analgesics to treat postoperative pain and provide prophylaxis against periprosthetic joint infection (PJI). − Specifically, bupivacaine-loaded UHMWPE implants could release clinically relevant drug doses for pain management in the immediate postoperative period . Clinically, intraarticular bupivacaine is widely used as a bolus injection and in a sustained-delivery formulation (Exparel, Pacira Pharmaceuticals, CA) to effectively manage postoperative pain associated with total joint replacement .…”