3D printed hydrogel/bioceramics core/shell scaffold with NIR-II triggered drug release for chemo-photothermal therapy of bone tumors and enhanced bone repair

Abstract

The treatment of bone defect caused by osteosarcoma remains an intractable problem. Scaffolds with multi-functions are the potential candidates to kill recurrent tumor and to repair the bone defects after tumorectomy. However, most of these scaffolds employed photothermal therapy using near‐infrared laser inthe first biological window (NIR‐I)with intrinsic poor tissue penetration depth. Some scaffolds loading drugs for chemotherapy generally lack the accurate control of on-demand drugs release to reduce the side effects and enhance the therapeutic efficacy. Herein, 3D printed gelatin/bioceramics core/shell scaffolds were developed with doxorubicin (DOX) loaded gelatin as the core part and SrCuSi4O10 (SC) nanosheets/beta-tricalcium phosphate (β-TCP) as the shell part of the printed filaments. SC nanosheets endowed the scaffolds with photothermal therapy under NIR-IIlaser irradiation. Simultaneously, the generated extensive hyperthermia could induce the gel-sol transition of the gelatin in the core part of the filaments, which subsequently triggered the on-demand DOX release from the loosened gelatin achieving chemo-photothermal therapy. The in vitro and in vivo data demonstrated that chemo-photothermal therapy showed a synergetic effect on anti-tumor. Additionally, the degradation/release of gelatin from the filaments resulted in the hollow channels in the scaffold, which provided clear architectural cues for promoting the ingrowth of bone tissues. Meanwhile, the degradation of the SC nanosheets contributed to the sustained release of bioactive ions (Sr, Cu and Si), which further enhanced vascularized bone regeneration. All these results indicated that the 3D printed DOX loaded gelatin-TCP/SC scaffolds had a great potential application for the treatment of bone defects caused by osteosarcoma in effective killing cancer cells and repairing tumor-induced bone defects.