Interfacial Engineering of a NaGdF₄@NaYF₄:Nd³⁺-Reinforced PVA/Chitosan Janus Hydrogel for Osteosarcoma and Osseointegration via the Entrapment of Strontium in Bisphosphonates

Postoperative impacts after osteosarcoma excision such as tumor recurrence and critical-sized bone defects continue to pose significant therapeutic challenges. Conventional implants employed to treat these defects often pose negligence in eliminating the residual tumor cells. The current study aims to address these constraints through the development of a multifunctional Janus hydrogel. An alendronate strontium complex and NaGdF₄@NaYF₄:Nd³⁺ nanophosphors have been incorporated in the poly(vinyl alcohol) (PVA)/chitosan matrix to attain the desired therapeutic and diagnostic functions. The apatite-forming ability evidenced through the SBF immersion studies alongside the multimodal imaging capabilities, namely, MRI, CT, and NIR luminescence of the Janus hydrogel, is deduced from the investigation. The ability of nanophosphors to generate localized hyperthermia of ∼56.1 °C under 808 nm near-infrared (NIR) irradiation led to the ablation of osteosarcoma cells. The conjugated alendronate supports intrinsic cytotoxicity in MG63 cells, even in the absence of irradiation. Furthermore, the biocompatibility and osteogenesis capacity of the hydrogel are evidenced through the enhanced HEK293 and MG63 cell proliferation under an osteogenic medium alongside the attainment of elevated levels of osteogenic markers such as RUNX2 and COL1 and calcium matrix mineralization. The overall findings highlight the complementary role of the Janus hydrogel in eliminating the tumor cells, promoting bone regeneration and angiogenesis.