Bifunctional scaffolds: strategic bridges coordinating osteosarcoma therapy and bone regeneration

Osteosarcoma (OS), recognized as the most common primary malignant bone tumor, presents substantial clinical challenges. The current standard of care, involving extensive surgical resection followed by adjuvant chemotherapy, often leads to critical-size bone defects and is hampered by high risks of local recurrence, metastasis and systemic toxicity. Conventional bone scaffolds are constrained by their purely mechanical role, lacking the inherent bioactivity required for a therapeutic function within the regenerative microenvironment. This significant and unresolved clinical challenge has driven the advancement of sophisticated biomaterial platforms aimed at achieving the dual objectives of effective osteosarcoma elimination and concurrent bone tissue regeneration. This review comprehensively explores the design principles of these scaffolds, detailing their use as a structural base and the integration of key components for antineoplastic strategies and osteogenesis. Furthermore, it delves into advanced smart material systems, including stimuli-responsive drug release platforms and 3D printing technologies for creating patient-specific implants. The discussion also encompasses the critical in vitro and in vivo evaluation models used to assess the efficacy of these platforms. Finally, the review addresses the current challenges in balancing oncotherapy with regeneration and provides insightful perspectives on the future of this promising field, highlighting the potential of these engineered scaffolds to serve as strategic bridges connecting tumor ablation to functional bone reconstruction.