Vascularization plays an important role in the initial stage of triggering the bone defects repair. The combination of bioactive small molecule drugs and biomaterials has been a powerful strategy for...

The clinical treatment of infectious bone defects is difficult and time-consuming due to the coexistence of infection and bone defects, and the simultaneous control of infection and repair of bone defects is considered a promising therapy. In this study, a dual-drug delivery scaffold system was fabricated by the combination of a three-dimensional (3D) printed scaffold with hydrogel for infected bone defects repair. The 3D printed polycaprolactone scaffold was incorporated with biodegradable mesoporous silica nanoparticles containing the small molecular drug fingolimod (FTY720) to provide structural support and promote angiogenesis and osteogenesis. The vancomycin (Van)-loaded hydrogel was prepared from aldehyde hyaluronic acid (AHA) and carboxymethyl chitosan (NOCC) by the Schiff base reaction, which can fill the pores of the 3D-printed scaffold to produce a bifunctional composite scaffold. The in vitro results demonstrated that the composite scaffold had Van concentration-dependent antimicrobial properties. Furthermore, the FTY720-loaded composite scaffold demonstrated excellent biocompatibility, vascularization, and osteogenic ability in vitro. In the rat femoral defect model with bacterial infection, the dual-drug composite scaffold showed a better outcome in both infection control and bone regeneration compared to other groups. Therefore, the prepared bifunctional composite scaffold has potential application in the treatment of infected bone defects.