3D-printed vancomycin-eluting PGCL/MXene bifunctional scaffold for management of infected bone defects

The clinical management of infected bone defects remains a significant challenge in orthopedic surgery. In this study, we developed a multifunctional composite scaffold by integrating MXene (Ti₃C₂) nanosheets and vancomycin (Van) into a degradable poly(glycolide-co-caprolactone) (PGCL) polymer through precision 3D printing technology, with the aim of regenerating acutely infected bone defects. Systematic optimization established the optimal composition as 5 wt% Ti₃C₂ and 5 wt% Van within the degradable PGCL polymer. Compared with PGCL scaffolds, a significantly thicker mineralized layer could be deposited on the PGCL@5 %Ti₃C₂/5 %Van surface in simulated body fluid (SPF). The <i>in vitro</i> results showed that the PGCL@5 %Ti₃C₂/5 %Van scaffold had antibacterial properties, cytocompatibility, osteoblast differentiation and extracellular mineralization. The <i>in vivo</i> results showed that the PGCL@5 %Van/5 %Ti₃C₂ scaffold effectively inhibited infection caused by methicillin-resistant <i>Staphylococcus aureus (MRSA)</i> in bone defects and promoted bone repair. The potential mechanism of Ti₃C₂ in anti-inflammatory and osteogenic induction was investigated through transcriptome analysis. These results suggest that Ti₃C₂ is involved in the regulation of the PI3K‒Akt signalling pathway to increase osteogenic induction ability and regulate the inflammatory response by downregulating the NF-κB pathway through the deiodinase iodothyronine type II (DiO2). These findings indicate that the PGCL@5 %Ti₃C₂/5 %Van scaffold can enhance the regeneration of acutely infected bone defects.