3D-Printed poly(lactic acid)/magnesium scaffolds functionalized with chitosan-chlorhexidine gluconate microspheres...

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.