Engineering Osteosarcoma In Vitro: From Traditional Models to Biofabricated Platforms for Precision Medicine.

Osteosarcoma is a highly malignant primary bone tumor that predominantly affects adolescents. Despite the widespread application of standard treatment modalities, including surgical resection, chemotherapy, and radiotherapy, the long-term survival rate of patients remains unsatisfactory due to the high metastatic potential and drug resistance of the disease. In recent years, researchers have focused on developing more precise in vitro models that aim to better simulate the tumor microenvironment, thereby enhancing the effectiveness of drug screening and personalized therapy. This review summarizes the latest advances in osteosarcoma in vitro modeling, including the development of conventional two-dimensional culture systems, three-dimensional culture platforms, organoid models, and microfluidic chips designed to mimic the tumor microenvironment. Additionally, this review explores the application value of these models in drug screening, immune coculture systems, and personalized treatment strategies. The integration of multiomics data and artificial intelligence is also discussed as a means to optimize model design and facilitate precision oncology. Biomimetic in vitro models have the potential to more accurately replicate tumor heterogeneity, cell-cell interactions, and the complexity of the tumor microenvironment, thereby increasing the translational value of preclinical drug development. Finally, this review highlights the current challenges in the field, including the lack of standardized protocols, issues with model stability and reproducibility, and the practical integration of these models into preclinical research pipelines.