Advanced Strategies and Innovative Theragenerative Nano/Micro Biomaterials for Bone Cancer Therapy and Bone Tissue Regeneration with a Focus on Osteosarcoma Management

Osteosarcoma (OS), a highly malignant primary bone tumor, is a relatively rare cancer with an incidence of about 3.4 cases per million people annually, yet it remains the most common malignant bone tumor in children and adolescents. Current clinical treatments often fail to completely eradicate the tumor, resulting in recurrence and substantial bone loss. To address these challenges, advanced macro-, micro-, and nanoscale bioactive materials are increasingly needed in bone tumor management. These materials must not only replace lost tissue and integrate with host bone but also provide a supportive environment for osteoblast growth and healing. Biomaterial-mediated bone regeneration focuses on designing temporary scaffolds and injectable micro/nanosponges or gels that fill bone defects and replicate the native bone niche. Additionally, such biomaterials should offer therapeutic functions to eliminate residual cancer cells after resection. Enhancing the therapeutic index and treatment efficiency while simultaneously addressing bone loss is necessary for improving clinical outcomes in osteosarcoma management. This review highlights the most advanced strategies and innovative theragenerative nano- and microparticles containing biomaterials investigated for bone cancer management (killing bone tumor cells and/or repairing bone defects) focusing on osteosarcoma.