Abstract
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 (Ti(3)C(2)) 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% Ti(3)C(2) 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 %Ti(3)C(2)/5 %Van surface in simulated body fluid (SPF). The in vitro results showed that the PGCL@5 %Ti(3)C(2)/5 %Van scaffold had antibacterial properties, cytocompatibility, osteoblast differentiation and extracellular mineralization. The in vivo results showed that the PGCL@5 %Van/5 %Ti(3)C(2) scaffold effectively inhibited infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in bone defects and promoted bone repair. The potential mechanism of Ti(3)C(2) in anti-inflammatory and osteogenic induction was investigated through transcriptome analysis. These results suggest that Ti(3)C(2) 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 %Ti(3)C(2)/5 %Van scaffold can enhance the regeneration of acutely infected bone defects.