Degradable photothermal bioactive glass composite hydrogel for the sequential treatment of tumor-related bone defects: From anti-tumor to repairing bone defects

Abstract

To treat tumor-related irregular bone defects, the implanted biomaterials after surgery should combine the functions of both tumor therapy and bone regeneration. To address the requirement, double crosslinking injectable composite hydrogels based on Furan-Sodium Alginate/bis-maleimide-Polyethylene Glycol/Copper doped Bioactive Glass-ceramic Microspheres (SA/PEG-CuBGM) were prepared using Diels–Alder (DA) reaction and ionic crosslinking. The prepared composite hydrogel showed excellent photothermal effects and killed most tumor cells in vitro and inhibited tumor growth in mice at the early implantation stage. The photothermal effects were derived from the oxide formed by doping copper ions in bioactive glass, and the photothermal temperature could be controlled by the CuBGM concentration and power densities of near infrared (NIR). Next, the photothermal agent concentration decreased rapidly with the degradation of the material. Additionally, the Ca, Si and Cu released from CuBGM improved the capability to stimulate the osteogenic differentiation of mBMSCs by upregulating bone-related gene expression, significantly promoting new bone formation in a femoral defect model of rats. Therefore, as the sequential progress of photothermal treatment and osteogenesis promotion is realized, the SA/PEG-CuBGM composite hydrogel will demonstrate considerable potential to aid the development and application of implanted biomaterials to tumor-related bone defects.