Open questions on the 3D structures of collagen containing vertebrate mineralized tissues: A perspective

Our current understanding of the structures of vertebrate mineralized tissues is largely based on light microscopy/histology and projections of 3D structures onto 2D planes using electron microscopy. We know little about the fine details of these structures in 3D at the length scales of their basic building blocks, the inherent variations of structure within a tissue and the cell-extracellular tissue interfaces. This limits progress in understanding tissue formation, relating structure to mechanical and metabolic functions, and obtaining deeper insights into pathologies and the evolution of these tissues. In this perspective we identify and discuss a series of open questions pertaining to collagen containing vertebrate mineralized tissues that can be addressed using appropriate 3D structural determination methods. By so doing we hope to encourage more research into the 3D structures of mineralized vertebrate tissues.