Carboxylic acid-functionalized polycarbonates as bone cement additives for enhanced and sustained release of antibiotics

Abstract

Despite the good clinical outcomes of total joint replacements, prosthetic joint infections still remain a significant cause of implant failure. Primary prophylaxis is key to stemming this burgeoning problem and its associated complications. In this study, a series of bone cement formulations with enhanced antibacterial performance have been developed through the addition of carboxylic acid-functionalized polycarbonate block copolymers to commercially available bone cement. Block copolymer design features were specifically tailored to modulate the acidity for adsorption of antibiotic and phase separation of the copolymers within the polymerizing/hardening of the cement during application. The best performing polymers demonstrated sustained antimicrobial release for more than 259 days and 147 days against S. aureus and P. aeruginosa, respectively, compared to 70 days of activity seen with commercially available gentamicin-containing cement control; whilst in vitro gentamicin release was increased by 8-fold. Total porosity was also increased 3-fold from 4.3% to 12.5%, whilst maintaining the mechanical integrity, working characteristics and osteoblastic biocompatibility of bone cement. Taken together, carboxylic acid-functionalized polycarbonates represent a promising class of bone cement additives that can be used to enhance the antibacterial performance of the bone cement whilst maintaining mechanical strength and cellular biocompatibility.