BioMarrow: An accessible and reproducible 3D patient-derived bone marrow model for advancing research and clinical applications.

Preclinical models for multiple myeloma (MM) often fail to recapitulate the complexity of the bone marrow (BM) microenvironment, limiting their utility for drug testing and translational research. There is an urgent need for physiologically relevant, patient-adaptable platforms to support personalized therapeutic evaluation. We developed BioMarrow, a 3D ex vivo BM culture system using unmanipulated patient BM aspirates embedded in Matrigel. Culture conditions were optimized to sustain diverse hematopoietic, stromal and immune populations for up to 7 days. Spatial distribution, cytokine secretion and treatment responses were assessed via flow cytometry, immunohistochemistry, multiplex ELISA and cell viability assays. The model maintained key BM components characteristics of MM, supported stromal network formation and preserved cytokines such as IL-6 and TGF-β. Immune-effector cytokines were reduced, consistent with a tumour-permissive microenvironment. Drug testing with MM cell lines confirmed BioMarrow's ability to discriminate treatment sensitivity. BioMarrow captures essential features of the MM niche and offers a clinically relevant, short-term platform for ex vivo therapeutic screening. Its scalability and immune component preservation support future integration into personalized treatment workflows, including immunotherapy evaluation.