Induction of Carbodiimide Coupling of Alendronate to Chitosan with Samarium Entrapment and NaDyF ₄ @NaYF ₄ :Nd ^{3 <b>+</b>} in PVA Double-Layered Hydrogel for Photothermal Therapy and Bone Remodeling

The combination of challenges associated with osteosarcoma treatment emerges from the inadequacy of conventional cancer therapies to heal the extensive bone defects generated following tumor excision. On the other hand, the bone-regeneration approach lacks in mitigating the risk of tumor recurrence. This therapeutic gap demands the necessity of a multifunctional approach that simultaneously inhibits cancer recurrence and promotes the process of bone regeneration. The extensively employed traditional photosensitizers display limited anticancer activity and lack regenerative properties. These constraints are circumvented through the development of a bilayer Janus hydrogel that integrates NaDyF₄@NaYF₄:Nd³⁺ nanophosphors within a poly(vinyl alcohol) (PVA) layer, while a chitosan layer encompasses functionalized alendronate and samarium. This multifunctional hydrogel, developed through a freeze-thaw process, exhibited strong photothermal activity and also demonstrated efficacy in eradicating MG63 osteosarcoma cells <i>in vitro</i>. Further, the typical extracellular matrix resemblance characteristic of the hydrogel demonstrated better cell proliferation and osteogenic differentiation of MG63 cells and promoted vascularization in the CAM model. Moreover, the presence of lanthanides in the hydrogel facilitates multimodal imaging characteristics of magnetic resonance imaging (MRI), computed tomography (CT), and near-infrared (NIR) luminescence. Thus, the synergistic effect of encompassing localized cancer therapy and efficient bone restoration offers a promising strategy to treat bone tumors.