SHOULD ANTIBIOTIC-LOADED CERAMIC BONE GRAFT SUBSTITUTES BE CONSIDERED SUSTAINED-RELEASE DEPOTS? A CRITICAL REANALYSIS OF GENTAMICIN RELEASE DATA INFORMING CLINICAL USE

Background Antibiotic-loaded ceramic bone grafts (ACBGs) are widely assumed to provide prolonged local antimicrobial protection, with claimed concentrations above the minimum inhibitory concentration (MIC) for up to 28-42 days. These expectations strongly influence surgical planning and postoperative infection management. However, these claims are primarily derived from in vitro elution assays using simplified washout models, and their relevance to in vivo performance remains uncertain. This study aimed to analyse and compare the in vivo and in vitro release and modelled characteristics of gentamicin from two commercially available ACBGs. Methods Gentamicin-loaded hydroxyapatite/calcium sulfate (HA–CS) and calcium sulfate (CS) composites were investigated using a murine implantation model and standardized in-vitro elution assays. Gentamicin content in recovered depot material and elution media was quantified by LC-MS/MS. Model calculations were applied to assess how assay design influences estimated time above MIC. Results Both ACBGs released >98% of incorporated gentamicin within 6 hours and >99% within 24 hours in vivo. In vitro assays supported early depot depletion, with concentration–time profiles beyond 48 hours governed by serial dilution rather than antibiotic release. Model calculations show that the apparent time above MIC in in vitro assays used to support claims of prolonged antibiotic activity largely reflects assay design, not sustained release, indicating that freely administered antibiotics could produce similar profiles. Conclusions Neither ACBG demonstrated measurable sustained release beyond an initial 24-hour burst phase. This may have important clinical implications, as expectations of prolonged local antimicrobial protection are not supported by the cumulative release data showing rapid antibiotic depletion. Distinguishing artefacts arising from in vitro assay design and analytical limitations from true sustained depot release is critical for surgical decision-making to avoid overestimating local antimicrobial coverage and unjustified clinical confidence in implant or tissue protection.