Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation

This review decodes the biological basis of triple-negative breast cancer (TNBC) bone metastasis and critically examines how 3D bioprinted models can bridge mechanistic investigation and clinical translation. We first synthesize the osteolytic vicious cycle, multicellular microenvironmental crosstalk, and pre-metastatic niche remodeling that drive TNBC bone colonization, and then evaluate how bioprinting-based platforms can recapitulate these processes with greater spatial, mechanical, and cellular fidelity than conventional models. Traditional static research models fail to capture this dynamic spatiotemporal complexity, hindering understanding and treatment development. 3D bioprinting overcomes this by creating a biomimetic microenvironment. It uses hydrogel or composite scaffolds to replicate the bone matrix's mechanical properties and biochemical gradients. This integrates tumor cells, vascular networks, and bone stromal cells, dynamically modeling metastatic colonization. This bioprinted system serves as a high-efficiency drug screening platform, enabling systematic assessment of nano-drug delivery and strategies to overcome microenvironment-induced resistance. Clinically, 3D printing directly aids in developing patient-specific bone repair implants and surgical guides for reconstructing metastatic lesions. Critically, these models bridge fundamental research and clinical translation. They allow spatiotemporal visualization/analysis of key signaling pathways in metastasis and facilitate high-throughput screening of bone-targeted combination therapies. Rather than presenting a newly established experimental model, this article provides a focused review of current advances, unresolved technical barriers, and future translational directions for TNBC-oriented 3D bioprinting in bone-metastasis research.