Calcium Phosphate-Based Biomaterials for Osteogenesis and Osteosarcoma Management: Drug Delivery Strategies, Therapeutic Molecules and Challenges in Clinical Translation

Osteosarcoma (OS) is one of the most common malignant bone tumors in adolescents. Despite advances in surgical resection and systemic chemotherapy, residual microscopic disease may contribute to local recurrence, while reconstruction of post-surgical bone defects remains a significant clinical challenge. Calcium phosphate (CaP)-based biomaterials are being investigated as local delivery platforms to simultaneously provide controlled anticancer therapy and promote bone regeneration. In this review, we present a critical overview of anticancer CaP biomaterials, focusing on three key aspects: (i) the OS tumor microenvironment, which limits the efficacy of conventional chemotherapeutic treatments and impairs bone regeneration; (ii) diverse drug-loading strategies that govern drug encapsulation and release kinetics; and (iii) a broad range of therapeutic agents incorporated into CaP matrices, including chemotherapeutic drugs, phytochemicals, trace elements, and immunomodulatory agents. Despite substantial progress in this field, clinically established CaP-based platforms that achieve controlled local anticancer delivery with validated bone-regenerative performance remain limited. Therefore, we critically evaluated the major translational barriers, manufacturing challenges, and regulatory considerations that must be addressed to facilitate the clinical translation of these multifunctional biomaterials from bench to bedside.