3D-Printed poly(lactic acid)/magnesium scaffolds functionalized with chitosan-chlorhexidine gluconate microspheres for antibacterial repair of infected bone defects.

The major challenge in infected bone defect repair is the difficulty in achieving infection control and bone regeneration simultaneously. In this study, a 3D-printed polylactic acid/magnesium (PLA/Mg) composite scaffold loaded with chitosan-chlorhexidine gluconate (CTS-CHG) microspheres was developed, and its antibacterial, osteogenic, and biosafety properties were systematically evaluated. CTS-CHG microspheres were prepared by ionic crosslinking and immobilized onto porous PLA/Mg scaffolds. The morphology, physicochemical properties, drug release behavior, antibacterial activity, cytocompatibility, osteogenic performance, and preliminary in vivo biosafety of the scaffold were then assessed. The results showed that the PLA/Mg/CTS-CHG scaffold possessed a stable porous structure, suitable mechanical strength, and sustained release profiles of Mg2+ and CHG. Compared with the PLA and PLA/Mg groups, the composite scaffold exhibited markedly enhanced antibacterial activity, with a stronger inhibitory effect against Staphylococcus aureus than against Escherichia coli. Meanwhile, the scaffold maintained good cytocompatibility and did not show evidence of compromising the osteogenic advantage observed in the PLA/Mg scaffold. In vivo, the PLA/Mg/CTS-CHG scaffold showed improved bone repair under infected conditions, which may have been associated with its antibacterial performance. Zebrafish and rat evaluations further showed no obvious short-term abnormalities in oxidative stress-related signals, inflammatory cell-associated signals, developmental morphology, or major organ histology. In conclusion, the PLA/Mg/CTS-CHG scaffold integrated enhanced antibacterial capability with preserved osteogenic performance and represents a promising multifunctional scaffold for infected bone defect repair.