3D-Printed Scaffold Achieves Synergistic Chemo-Sonodynamic Therapy for Tumorous Bone Defect.

Various smart scaffolds have recently been developed to address the regeneration of tumor bone defect. However, the recurrence of residual tumor cells poses a serious challenge to postoperative management, highlighting the need for effective therapeutic interventions. In this study, a multifunctional antitumor nanoplatform (Ti3C2/CuO2) for synergistic chemo-sonodynamic tumor therapy was developed and then rationally integrated into a poly(l-lactic acid) (PLLA) scaffold via selective laser sintering. CuO2 not only releases Cu2+ ions to facilitate chemodynamic antitumor therapy through the Fenton reaction but also generates H2O2, which further oxidizes Ti3C2 to produce TiO2 sonosensitizers. More importantly, the carbon-based substrates after oxidation of Ti3C2 have created favorable conditions for carrier transmission in the sonodynamic process, thereby amplifying the sonodynamic therapy. Additionally, moderate local hyperthermia form periodic sonodynamic therapy produces moderate localized heat therapy to further stimulate bone tissue regeneration. Meanwhile, the sustained release of bioactive ions (such as Cu and Ti ions) from the scaffold also fosters vascularization, further accelerating bone regeneration. This work presents a viable approach to developing multifunctional scaffolds for repairing tumorous bone defects.