Bone tissue is an organic-inorganic composite material that provides mechanical support and protection for our bodies. Its impressive mechanical properties arise from the hierarchical organization of the organic collagen matrix that is mineralized with ultrathin, aligned inorganic crystals of carbonated hydroxyapatite. Despite its importance to the human body, still relatively little is understood about the mechanisms by which collagen mineralization occurs and what the respective roles are of the collagen and other non-collagenous proteins (NCPs) in directing this process. This is because the process is complex: different stages occur over multiple length scales, and many different components are involved. So far, studying collagen mineralization has mainly relied on analyses that require sample-altering preparation methods and lack information about the dynamics; or on simplified in vitro systems that do not necessarily represent what happens in the native bone environment. To understand the role of NCPs in collagen mineralization, we need to study their dynamics and structural interactions with the highest possible resolution and in an environment as close as possible to native bone. Here we build a tissue-engineered bone that has the main characteristic of bone. This model system allowed us to monitor the development of the extracellular matrix in the presence of the different proteins. Besides the unprecedented details that this system provides on the role of selected NCPs in collagen mineralization, it will significantly impact how bone defects and mineralization are studied, and open the door to new treatments for related diseases such as osteogenesis imperfecta and Ehlers-Danlos syndrome.
