Synergistic antibacterial drug elution from UHMWPE for load-bearing implants

Abstract

Total joint replacement is a successful procedure for restoring the patient's musculoskeletal mobility and quality of life, but it carries the risk of severe peri-prosthetic joint infections (PJI) and is accompanied by post-operative pain. Cocktails of multiple drugs are often used for prevention/treatment of PJI and for addressing pain. Local drug delivery systems are promising for improving the outcome of the treatment and decreasing the side effects of systemic drugs. To this end, the ultra-high molecular weight polyethylene (UHMWPE) bearing surface of the joint implant is here proposed as a platform for simultaneous release of multiple therapeutics. The combined use of non-antibiotic drugs and antibiotics, and their incorporation into UHMWPE allows to obtain novel antibacterial implant materials. The combined elution of analgesics and antibiotics from UHMWPE is found to be synergistically effective in eradicating Staphylococcus aureus, as the non-antibiotic compound significantly enhances the antibacterial activity of the antibiotic. The drug properties and the employed method for their incorporation into UHMWPE are found to dictate the morphology, thus the mechanical properties of the resulting material. By adopting various fabrication methods, novel formulations showing an enhanced antibacterial activity and outstanding mechanical properties are here proposed to amplify the functionality of polymeric implant materials.