Interaction mechanisms between antibiotics and calcium phosphate cements as pharmacologically active bone graft substitutes

Calcium phosphate cements (CPCs) are widely used as medical devices for treating bone defects due to their high biocompatibility and ease of clinical application. Their porous structure and low setting temperature make them suitable as drug delivery systems, enabling high local drug concentrations while minimizing systemic side effects. However, successful application requires predictable drug release and a thorough understanding of drug-cement interactions. This study examined the interactions of vancomycin and gentamicin with three hydroxyapatite-forming CPCs. Investigations focused on the strength and nature of these interactions and the effects of drug addition on solubility, setting behavior, microstructure, rheological and mechanical properties of the cements, as well as drug release profiles, and antimicrobial activity. Over 34 days, both antibiotics were largely released from all cements and maintained antimicrobial efficacy against typical bone infection pathogens. Release profiles varied significantly depending on cement type and antibiotic. Gentamicin notably prolonged setting times and influenced mineral phase development. In contrast, the effects on injectability, microstructure, final phase composition, and mechanical strength were minor. These findings highlight the potential of antibiotic-modified CPCs for localized treatment of bone infections. Their clinical use appears promising, provided that the specific properties of each drug-cement combination are carefully considered. STATEMENT OF SIGNIFICANCE: This study provides a comprehensive analysis of how the two clinically relevant antibiotics, vancomycin and gentamicin, interact with three distinct calcium phosphate cements that form hydroxyapatite in situ. By elucidating the nature and strength of drug-cement interactions, the work provides critical insights into how these interactions influence key material properties, including setting kinetics, phase evolution, microstructure, mechanical performance, and drug release behaviour. The findings are of high clinical relevance, as they inform the design of antibiotic-loaded mineral bone cements with predictable performance characteristics for the local treatment of osteomyelitis and other bone-related infections. The study underscores the need for individualized assessment of drug-carrier compatibility to ensure both material integrity and therapeutic efficacy, offering significant potential for improving patient outcomes in orthopaedic and trauma surgery.