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

Abstract

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.