Nanocomposite multifunctional hydrogel for suppressing osteosarcoma recurrence and enhancing bone regeneration

Abstract

Osteosarcoma (OS) is the most prevalent primary malignancy of bone. Inhibition of OS recurrence and subsequent bone formation after surgery remains a challenge for decades. Innovative biomaterials with the dual function of tumor therapy and bone regeneration have emerged as a promising strategy for OS treatment. We developed a bioactive nanoparticle (MDA-NPs) composed of magnesium oxide nanoparticle (M-NPs) core and 2-Aminoethyl methacrylate (2-AM) grafted polydopamine (PDAM) shell. The phosphonate modified methacrylamide chitosan (CMP) and polyacrylamide (PAM) were prepared to form a pre-gel, and then a series of MDA-NPs nanocomposite with 0 mg/mL, 0.5 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL were incorporated and coded as CMP@PAM, 0.5NP/CMP@PAM, 2.5NP/CMP@PAM, 5NP/CMP@PAM, 10NP/CMP@PAM, respectively. We found that 5NP/CMP@PAM hydrogel showed a balanced photothermal effect, mechanical property, and osteogenesis for MDA-NPs can be used as a co-crosslinker, photothermal agent, and Mg2+ reservoir. Human OS cells (143B) could be efficiently inhibited by 5NP/CMP@PAM hydrogel with near-infrared (NIR) laser irradiation, achieving complete suppression of tumor recurrence in vitro and in vivo. The released Mg2+ efficiently promotes the osteogenic activities of mouse embryo osteoblast precursor cells (MC3T3-E1) and 5NP/CMP@PAM hydrogels exhibit highly effective bone repair performance in a critical cranial defect rat model. In conclusion, the 5NP/CMP@PAM hydrogel demonstrated excellent dual functions of suppressing OS recurrence and repairing bone defects. This novel multifunctional bioactive hydrogel provides an encouraging idea of synergistic postoperative treatment of OS.