An Additive to PMMA Bone Cement Enables Postimplantation Drug Refilling, Broadens Range of Compatible Antibiotics, and Prolongs Antimicrobial Therapy

Abstract

Poly(methyl methacrylate) (PMMA) bone cement is used in several biomedical applications including as antibiotic-filled beads, temporary skeletal spacers, and cement for orthopedic implant fixation. To mitigate infection following surgery, antibiotics are often mixed into bone cement to achieve local delivery. However, since implanted cement is often structural, incorporated antibiotics must not compromise mechanical properties; this limits the selection of compatible antibiotics. Furthermore, antibiotics cannot be added to resolve future infections once cement is implanted. Finally, delivery from cement is suboptimal as incorporated antibiotics exhibit early burst release with most of the drug remaining permanently trapped. This prolonged subtherapeutic dosage drives pathogen antibiotic resistance. To overcome these limitations of antibiotic-laden bone cement, insoluble cyclodextrin (CD) microparticles are incorporated into PMMA to provide more sustained delivery of a broader range of drugs, without impacting mechanics. PMMA formulations with and without CD microparticles are synthesized and filled with one of three antibiotics and evaluated using zone of inhibition, drug release, and compression studies. Additionally, the ability of PMMA with microparticles to serve as a refillable antibiotic delivery depot is explored. Findings suggest that addition of CD microparticles to cement promotes postimplantation antibiotic refilling and enables incorporation of previously incompatible antibiotics while preserving favorable mechanical properties.

Keywords: bone cements; cyclodextrin; drug delivery; infections; musculoskeletal.