02176nas a2200217   4500000000100000000000100001008004100002260001200043653002700055653003000082100002100112700002000133700002100153700002800174245006200202856005500264300001200319490000600331520160700337022001401944       2025                            d  c2025-0810aBiomedical Engineering10aHaematopoietic stem cells1 aTheodora Rogkoti1 aHannah Donnelly1 aMatthew J. Dalby1 aManuel Salmeron-Sanchez00aMechanical signatures and models of the bone marrow niche  uhttps://www.nature.com/articles/s44222-025-00305-6  a697-7130 v33 aThe bone marrow is a complex tissue with distinct cellular and mechanical heterogeneity, serving as the primary site for haematopoiesis. Under certain conditions, such as on the onset of mutations to healthy cells or alterations to the environment, the bone marrow can also become the origin of haematological malignancies, often characterized by uncontrolled self-renewal of hematopoietic stem cells, overproduction of immature progeny and remodelling of the tissue microenvironment. This remodelling alters the composition and mechanics of the extracellular matrix (ECM), facilitating the proliferation and metastasis of leukaemic cells. The elastic and dissipative properties of the ECM are hallmarks of both health and disease progression in different tissues. However, studying the mechanical properties of bone marrow is difficult owing to inaccessibility in situ. Advanced three-dimensional bioengineered models offer a way to recapitulate the mechanical properties of the bone marrow, but it remains challenging to incorporate the elastic and viscous components. Understanding the physiological and disease-specific mechanical ECM signatures is crucial for advancing bone marrow research and for developing therapeutics. In this Review, we explore the structure–function relationship of the bone marrow, emphasizing its complex mechanical behaviour, and discuss the bioengineered models that recapitulate the mechanical properties in the healthy and diseased bone marrow niche, stressing the importance of replicating ECM physiological and pathological mechanical signatures in the future.  a2731-6092