The microstructure and nanostructure of bone and the nanostructured material used in bone regeneration. (a) At the macroscopic level, bone consists of a dense shell of cortical bone with porous cancellous bone at both ends. (b) Repeating osteon units within cortical bone. In the osteons, 20–30 concentric layers of collagen fibers, called lamellae, are arranged at 90° surrounding the central canal, containing blood vessels and nerves. (c) Collagen fibers (100–2000 nm) are composed of collagen fibrils. The tertiary structure of collagen fibrils includes a 67 nm periodicity and 40 nm gaps between collagen molecules. The hydroxyapatite (HA) crystals are embedded in these gaps between collagen molecules and increase the rigidity of the bone. Nanostructures with the features of nanopattern (d), nanofibers (e), nanotubers (f), nanopores (g), nanospheres (h), and nanocomposites (i) with structural components with a feature size in the nanoscale. Reprinted by permission from Macmillan Publishers Ltd., Bone Research, Gong et al. [56], copyright © 2015.