Osteosarcoma stays probably the most prevalent and aggressive main malignant bone tumor, primarily affecting adolescents and younger adults. Regardless of developments in surgical strategies and chemotherapeutic regimens, sufferers with metastatic or recurrent illness nonetheless have a 5-year survival charge of lower than 30 % [1], [2]. This underscores the pressing want for more practical and better-integrated therapeutic methods. Typical therapies typically fail to handle two main challenges on the similar time: full tumor eradication and purposeful bone regeneration. This drawback is especially evident in instances with giant resection-induced defects and sophisticated tumor–bone microenvironment interactions.
Lately, composite engineering has emerged as a sensible technique to bridge these twin therapeutic wants. It combines the distinct benefits of nanoscale precision, microscale architectural steerage, and macroscale mechanical assist. Utilizing these options, superior biomaterials might be designed to coordinate tumor suppression, immune modulation, and bone restore inside a single therapeutic platform [3], [4]. These programs cannot solely ship chemotherapeutics or gene-editing brokers with exact timing and site, but additionally present mechanical scaffolds and biochemical cues that promote osteogenesis [5], [6], [7], [8]. Furthermore, the incorporation of stimuli-responsive launch mechanisms and biomimetic design ideas presents unprecedented versatility for overcoming limitations related to systemic toxicity, drug resistance, and post-surgical nonunion [9], [10].
Importantly, osteosarcoma’s complicated interaction with the immune and skeletal programs presents each a problem and a chance. Tumor-associated immune evasion, hypoxic metabolism, and osteolytic signaling create a hostile microenvironment that resists monotherapies[8], [11], [12]. Nonetheless, rising proof means that multifunctional biomaterials can actively reshape this microenvironment. They achieve this by selling antitumor immunity, regulating redox and metabolic pathways, and restoring bone homeostasis [13], [14], [15], [16], [17]. These advances place composite-based methods not merely as passive drug carriers, however as lively therapeutic brokers able to coordinating built-in organic responses.
In contrast with latest critiques on nanomaterials for osteosarcoma, this text presents a complementary perspective in 4 respects [18], [19]. First, it proposes a cross-scale composite-engineering framework that {couples} materials scale (nano/micro/macro) with immunomodulation, bone regeneration, and precision remedy. Second, it organizes the osteosarcoma tumor-immune microenvironment into actionable axes and aligns materials design levers to every axis. Third, it defines synergy standards and an evidence-grading rubric to distinguish real synergy from easy additivity. Fourth, it integrates mechanical/osteogenic necessities with oncologic endpoints (together with radiosensitization) right into a single choice map. Collectively, these parts set up a coherent body to situate prior findings and to tell subsequent materials design.
This assessment operationalizes the above framework right into a concise studying information. We specify the inclusion focus (osteosarcoma fashions reporting quantitative oncologic and osteogenic endpoints), define how research are organized by materials scale and supply modality, and make clear the grading ideas used to interpret synergy. We then study multifunctional integration, metabolic–bone coupling, and gene–mechanical interactions, and shut with key translational challenges and future instructions. (Graphical Summary)
