A Doxorubicin‐Loaded Liposomes Baghdadite System for Localized Osteosarcoma Therapy and Bone Regeneration

Osteosarcoma (OS) is a primary malignant bone tumor often treated by surgical resection and systemic chemotherapy, which can cause severe side effects and nonspecific drug distribution. Localized drug delivery via bone scaffolds offers a promising alternative but faces limitations such as poor drug retention, instability of therapeutics, and insufficient mechanical strength for bone repair. This study presents a multifunctional implant integrating doxorubicin (DOX)‐loaded liposomes into Baghdadite (Ca 3 ZrSi 2 O 9 , BAG) ceramics. Ion‐assisted plasma polymer (IPP) coating was employed to enhance liposome immobilization and control DOX release. BAG functionalized with DOX‐loaded liposomes (BAG/DOXlipo) significantly reduced OS cell viability, with enhanced efficacy observed in IPP‐coated samples. Notably, BAG/DOXlipo (with or without IPP) showed no cytotoxicity to human osteoblasts, supported sustained ion release, and promoted alkaline phosphatase activity and bone mineralization. Additionally, the BAG/DOXlipo system demonstrated antibacterial activity against common implant‐related pathogens. This platform uniquely combines mechanical robustness, osteoconductivity, and covalently bound liposomal chemotherapeutics to achieve localized tumor inhibition, bone regeneration, and infection control. It offers a promising strategy for OS treatment while minimizing systemic toxicity.