3D-printed scaffold loaded with baicalin exosomes promotes bone defect repair via mediating PRRX2 to alleviate inflammation.

Chronic nonunion of bone defects remains a significant challenge in orthopedic treatment. Artificial bone graft materials are expected to solve this problem due to their suitable degradation rate and good osteoconductivity. However, ROS and inflammation within the defect environment are important causes of implant failure. Exosomes derived from different preconditioned bone mesenchymal stem cells (BMSCs) have shown great potential in the treatment of various diseases. Here, we developed a 3D-β-TCP@BA-BMSC-exos scaffold that loaded baicalin-pretreated BMSC exosomes (BA-BMSC-exos) on a 3D-printed β-tricalcium phosphate scaffold (3D-β-TCP) for bone defect repair. In vitro experiments showed that BA-BMSC-exos enhanced proliferation, migration, and tube formation in HUVECs, as well as inhibited inflammation via mediating PRRX2. Moreover, 3D-β-TCP scaffolds loaded with BA-BMSC-exos clearly alleviated inflammation and promoted angiogenesis in a calvarial defect rat model. This study suggests that 3D-β-TCP scaffolds combined with BA-BMSC-exos are a promising strategy to enhance bone repair and regeneration.