Polyethylene Loaded With Dual Analgesics Has Synergistic Effects Against Staphylococci
- In this study, blocks of ultra-high molecular weight polyethylene (UHMWPE) were loaded with bupivacaine, tolfenamic acid, or both therapeutic agents
- UHMWPE loaded with either tolfenamic acid or bupivacaine had pronounced antibacterial activity against the adhesion of methicillin-sensitive Staphylococcus aureus and S. epidermidis
- UHMWPE loaded with both drugs yielded at least 1 to 2 log additional reduction of bacteria compared with UHMWPE loaded with one drug, indicative of antibacterial synergy
- This material is proposed for use as part of the bearing surface in total joint implants, providing post-arthroplasty pain management and short-term antibacterial prophylaxis
Periprosthetic joint infection after total joint arthroplasty is frequent and devastating, and surgeons commonly provide multimodal prophylaxis. This normally involves bolus and IV administration of various antibiotics and, in some cases, antibiotic-impregnated bone cement, all of which raise concerns about promoting bacterial resistance.
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In previous in vitro research published in the Journal of Orthopaedic Research, Massachusetts General Hospital researchers loaded ultra–high-molecular-weight polyethylene (UHMWPE) with bupivacaine, usually intended for post-arthroplasty pain relief, and detected pronounced activity against methicillin-sensitive Staphylococcus aureus.
A similar study published in Materialia showed UHMWPE loaded with another analgesic, tolfenamic acid, was effective against various strains of Staphylococci.
Now the team has found UHMWPE loaded with both agents provides substantially higher in vitro antibacterial activity compared with the single-drug counterparts. Dmitry Gil, PhD, formerly a research fellow in the Harris Orthopaedics Laboratory at Mass General, Ebru Oral, PhD, associate director of the Laboratory, and colleagues report in the Journal of Biomedical Materials Research, Part B.
Blocks of medical-grade UHMWPE were loaded with tolfenamic acid and/or bupivacaine, and their antibacterial activity was assessed with the "daughter cell" method. That assay measures the ability of a material to hinder bacterial adhesion, maturation of biofilms, and subsequent release of planktonic bacteria—daughter cells—in the acute postsurgical period.
The key observations were that:
- UHMWPE loaded with either tolfenamic acid or bupivacaine had pronounced antibacterial activity against the adhesion of methicillin-sensitive S. aureus and S. epidermidis
- UHMWPE loaded with both drugs yielded at least 1 to 2 log additional reduction of daughter cells compared with single-drug UHMWPE, indicative of antibacterial synergy
- Tensile and wear testing showed the mechanical and wear properties of the dual-therapeutic eluting UHMWPE were feasible for incorporation with joint replacement implants
- Osteoblast viability in the presence of the dual drug–loaded UHMWPE was higher than 70%, so the material is not expected to be cytotoxic
All tested formulations of dual drug–loaded UHMWPE showed similar antimicrobial activity, suggesting the observed synergy doesn't depend on the drug ratio when eluted at the range of concentrations studied.
If confirmed in animal studies, the high antibacterial activity should allow the design of tolfenamic acid/bupivacaine-loaded implants that provide post-arthroplasty antibacterial prophylaxis and pain management.
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