Local vancomycin is increasingly used in orthopaedic procedures to increase antimicrobial exposure at the surgical site, but the concentration at which direct intra-articular exposure damages intact cartilage remains uncertain. This study aimed to determine whether intra-articular vancomycin produces concentration-dependent histopathological injury in New Zealand White rabbit knee cartilage. Twenty-eight male rabbits were randomised to saline control or vancomycin at 2.5, 5, or 7.5 mg/mL and observed for 14 days. Safranin-O/Fast Green-stained cartilage was assessed by blinded observers using Modified Mankin scoring and Osteoarthritis Research Society International grading. All animals completed follow-up without clinical infection or systemic adverse events. Mean Modified Mankin scores were 2.14 ± 0.69, 4.29 ± 1.25, 4.29 ± 1.98, and 7.71 ± 2.36 in the control, 2.5, 5, and 7.5 mg/mL groups, respectively; severe lesions occurred only at 7.5 mg/mL, affecting four of seven specimens. These findings demonstrate a concentration-related in vivo cartilage safety signal and provide tissue-level evidence that complements recent chondrocyte toxicity and local vancomycin pharmacokinetic studies.
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