Dual antibiotic PLGA microspheres for the treatment of traumatic osteomyelitis.

Traumatic osteomyelitis (TO) treatment remains challenging due to biofilm formation and poor antibiotic penetration. We developed poly(lactic-co-glycolic acid) (PLGA) microspheres co-loaded with moxifloxacin/rifampicin (M/R-P) to address these limitations. Key findings: In vitro: The microspheres showed (1) no cytotoxicity (CCK-8 assay; live/dead staining; cytoskeletal staining; SEM visualization), and (2) no inhibition of osteogenic potential (ALP activity).In vivo: M/R-P microspheres significantly reduced MRSA burden ( 8 ± 3 × 10³ CFU/g) compared to debridement-only controls (3143 ± 727 × 10³ CFU/g; p < 0.0001), and near-complete infection resolution (histopathology). Conclusion: These results demonstrate that the M/R-P microspheres possess excellent safety profiles, favorable cytocompatibility, and remarkable antibacterial efficacy. The findings confirm the feasibility of our innovative approach using PLGA as a drug delivery carrier for localized antibiotic therapy in chronic osteomyelitis treatment, achieved through technological optimization for combined antibiotic administration. This provides a novel strategic direction for ultimately overcoming the clinical challenge of traumatic osteomyelitis.