Silicate Biomaterials‐Induced Bone Marrow Organoids for Tissue Regeneration

ABSTRACT The bone marrow is essential for immune function, hematopoiesis, and skeletal system. The emergence of bone marrow organoids (BMOs) holds promise for addressing bone‐related deficiencies, although maintaining BMOs homeostasis is still challenging, and their efficacy for tissue regeneration remains uncertain. Silicate biomaterials can provide distinctive biochemical clues by releasing bioactive ions, which are beneficial for regulating stem cell behaviors and developing cell functions. In this study, harnessing the bioactivities of silicate biomaterials, we engineered functional BMOs through the culture of mesenchymal stem cells (MSCs) and endothelial cells in a chemically defined medium, incorporating with calcium silicate nanowires (CS) and magnesium silicate nanospheres (MSS). The resulting BMOs demonstrated robust preservation of endothelial networks, increased self‐renewal of the mesenchymal compartment, and positive effects on hematopoietic stem cells. Co‐culture experiments revealed that the engineered BMOs can significantly improve the activities of chondrocytes, MSCs, and Schwann cells, which are pivotal for tissue regeneration. Furthermore, the silicate biomaterials upregulated gene expression and signaling pathways in the domains of osteogenesis and angiogenesis. In a rabbit osteochondral repair model, BMOs induced by MSS notably enhanced osteochondral regeneration. Our study reveals the critical role of silicate biomaterials in augmenting BMOs homeostasis and function, providing an innovative and compelling strategy for future tissue regeneration.