Antibiotic-Loaded Uhmwpe for Sustained Release and Enhanced Efficacy

Introduction Periprosthetic joint infection (PJI) affects up to 4% of all total joint arthroplasties. The standard treatment, a two-stage revision, employs antibiotic-loaded bone cement spacers that exhibit a high initial burst release of antibiotics, followed by a rapid decline. Vancomycin HCl and gentamicin sulfate are the most commonly used antibiotics in PJI treatment but still display suboptimal release kinetics. This study aimed to develop and evaluate single- and dual-antibiotic-loaded ultra-high molecular weight polyethylene (UHMWPE) with sustained antibiotic release and preserved mechanical integrity. Methods Antibiotic-loaded polyethylene (ABX-PE) was fabricated by incorporating submicron gentamicin sulfate, or a combination of gentamicin sulfate and vancomycin HCl, into UHMWPE. Antibiotic release was measured in vitro over six months. Mechanical properties were tested according to ASTM standards and compared with commercial UHMWPEs. Kinetic models were applied to the release data, and a one-compartment pharmacokinetic model was used to estimate intra-articular antibiotic concentrations. Results were compared with published release profiles of commercial dual-antibiotic-loaded bone cement. Results Both gentamicin and the combination of vancomycin and gentamicin exhibited sustained release for six months. Release kinetics followed zero-order, Korsmeyer–Peppas, and Hixson–Crowell models. After six months, modeled intra-articular concentrations were at least 256× MIC for gentamicin and 48× MIC for vancomycin, whereas benchmark bone cement data showed rapid declines in antibiotic levels. Mechanical testing for dual ABX revealed no significant changes in tensile strength (p > 0.05) and a significant increase in elongation at break (p < 0.001) compared with highly crosslinked (100 kGy) remelted UHMWPE. Conclusion Both single and dual-ABX-PE demonstrated prolonged, therapeutic-level antibiotic release while maintaining mechanical properties comparable to standard UHMWPEs. These findings support its potential as an alternative to bone cement spacers in two-stage PJI revision, addressing the limitations of current antibiotic release profiles.