3D-printed MXene-incorporated scaffolds as a bioenergetic metabolism regulator for bone regeneration

Bone defects accompanied by inadequate energy supply remain a critical challenge, driving the development of biomaterials that actively regulate mitochondrial energy metabolism. The unique physicochemical and antioxidant properties of MXenes have attracted extensive attention in bone tissue engineering. However, whether MXene modulates mitochondrial bioenergetics to drive osteogenesis in bone marrow-derived mesenchymal stem cells (BMSCs) has yet to be fully elucidated. Here, a series of polycaprolactone (PCL) scaffolds incorporating Ti 3 C 2 MXene nanosheets (0, 0.5, 1.0, and 2.0 wt%) were fabricated via three-dimensional (3D) printing. Among these, the 1.0 wt% MXene scaffold (P1.0M) achieved a favorable combination of interconnected porous architecture, improved mechanical properties, and enhanced hydrophilicity. In vitro , P1.0M promoted the adhesion, proliferation, and osteogenic differentiation of BMSCs. Mechanistically, P1.0M enhanced mitochondrial bioenergetics, as evidenced by increased oxidative phosphorylation (OXPHOS), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (ΔΨm), while effectively scavenging reactive oxygen species (ROS) to preserve mitochondrial integrity under oxidative stress. Furthermore, P1.0M enhanced cellular bioenergetics and osteogenesis in a protein kinase B (AKT)-dependent manner. In vivo , P1.0M accelerated bone repair in rat tibial defects. Collectively, these findings position this mitochondrial energy metabolism-targeted scaffold as a promising strategy for energy-demanding bone defects.