Dual-controlled-release dual-antibiotic-loaded bone scaffolds: Development and in vivo/in vitro study

The treatment of infectious bone defects (IBDs) is a major challenge in orthopedics, with infection control and defect repair as the two primary treatment goals. The development of three-dimensional (3D)-printed bone scaffolds capable of sustained and stable antibiotic release is an effective strategy for treating such defects. Specifically, the antibiotic loading method and the concentration of released antibiotics significantly affect infection control and bone repair outcomes. In this study, The double antibiotic microspheres were prepared by the double emulsion-solvent evaporation method. Moxifloxacin/ Rifampicin were encapsulated by poly(lactic-co-glycolic acid) (PLGA) to form RM-PLGA. Subsequently, different concentrations of RM-PLGA and basic fibroblast growth factor (bFGF) were loaded onto a 3D-printed triply periodic minimal surface (TPMS) titanium scaffold (TiS) with a graded porosity design. The loading of different concentrations of RM-PLGA and bFGF onto the 3D-TPMS TiS enabled the dual-controlled release of two antibiotics and enhanced the stability of the antibiotic release. In vitro, results showed that RM-PLGA/bFGF(GelMA)@TiS exhibited strong antimicrobial properties, cytocompatibility, and the capacity for osteoblast differentiation and extracellular mineralization. In vivo,RM-PLGA/bFGF(GelMA)@TiS was effective in inhibiting infections induced by Staphylococcus aureus (SA) while promoting osteogenesis and angiogenesis. These results suggest that RM-PLGA-2/bFGF(GelMA)@TiS can stably release antibiotics to achieve the therapeutic goals of infection control and promotion of osteogenesis and angiogenesis.