Abstract
Osteosarcoma is a highly aggressive bone malignancy with poor prognosis due to high metastasis and drug resistance. Conventional treatments often result in systemic toxicity and limited efficacy, highlighting the need for more precise and integrative approaches. Biomaterials with excellent biocompatibility and functional tunability have emerged as promising tools to enhance local therapy and support bone regeneration. This review summarizes recent advances in the application of natural, synthetic and composite biomaterials in four key areas: drug delivery, gene therapy, immunotherapy and post-resection bone repair. To provide a systematic perspective, we compiled and classified 64 representative studies published between 2021 and 2025, comparing biomaterial-based delivery strategies ranging from single-material carriers to multifunctional composite platforms. Particular focus is given to stimuli-responsive systems and scaffolds that integrate antitumor activity with regenerative capacity. By outlining emerging strategies and material platforms, this review offers a concise reference for the rational design of biomaterials addressing the dual challenge of tumor eradication and skeletal reconstruction. Interdisciplinary collaboration will be key to advancing these systems toward clinical application.