A 3D Cell‐Free Bone Model Shows Collagen Mineralization is Driven and Controlled by the Matrix

Osteons, the main organizational components of human compact bone, are cylindrical structures composed layers mineralized collagen fibrils, called lamellae. These lamellae have different orientations, degrees organization, and mineralization where intrafibrillar extrafibrillar minerals intergrown into one continuous network oriented crystals. While cellular activity is clearly source organic matrix, recent in vitro studies call question whether cells also involved matrix suggest that this process could be simply driven by interactions mineral with extracellular matrix. Through remineralization demineralized bone complete multiscale reconstruction 3D structure composition osteon without involvement demonstrated. Then, cell-free system explored as a realistic, functional model for situ investigation matrix-controlled processes. Combined Raman electron microscopy indicate glycosaminoglycans (GAGs) play more prominent role than generally assumed matrix–mineral interactions. The experiments show organization part result its interaction developing mineral.