Besides the mechanical function, bones implicate clinical significance as an exclusive site for producing all types of blood cells and maintaining body homeostasis via continuous remodeling process. Such synthetic and metabolic activities are essentially regulated by the marrow, a spongy-like gelatinous tissue located at the inside of bone cavities. In depth understanding of bone marrow biology is urgently required in various fields of modern medicine while probing its microenvironments has been challenging because of anatomical inaccessibility and lack of relevant preclinical models. In this talk, I will introduce bioengineering approaches to create artificial bone marrow tissue models for studying bone marrow related stem/cancer cell biology. 3D hydrogel scaffolds fabricated by a novel crystal template-based method represent similar structural and semi-solid mechanical properties to bone marrow ECM, which in turn enhances natural function of human bone marrow stromal cells. Combining the 3D scaffolds with marrow-derived stromal cells, we demonstrated in vitro and in vivo bone marrow tissue analogues that recapitulate key biological processes in the bone marrow in a reproducible and analytical manner. Biomimetic design of scaffolds coupled with a powerful set of microfluidics, imaging, cellular engineering, and animal models are expected to provide unique opportunities to build realistic preclinical marrow tissue microenvironments that can accurately predict physiological responses and capture complex dynamic cellular processes in human bone marrow.