Structure and formation of amorphous calcium phosphate and its role as surface layer of nanocrystalline apatite: Implications for bone mineralization

We provide a critical review of the chemical composition and structure of synthetic and biogenic (bone/dentin mineral) nanocrystalline hydroxy-carbonate apatite (HCA). Such particles exhibit a “core–shell” organization, where an ordered HCA core is coated by a surface layer, whose nature is best captured by amorphous calcium phosphate (ACP), which is known to be a precursor phase of synthetic HCA, but whose role of bone/dentin mineralization has remained a most controversial subject. After reviewing the structure of each HCA and ACP component, as well as the most recent findings on their in vitro formation mechanisms, we examine the core–shell HCA organization further, with a focus on the disordered surface (“shell”) domain. In most of recent literature, the surface portion is often referred to as the “hydrated surface layer”, but without identifying its shared chemical and structural features of (synthetic) ACP. Unfortunately, that missing surface-layer/ACP equivalence obscures that the surface layer at the synthetic/biogenic nanocrystallites may simply constitute a remnant of the ACP phase from which the ordered HCA “core” nucleated. Although many topics reviewed herein have been investigated for more than six decades, several remain unsettled and heavily debated. Notably, decades-old articles offer suggestions that have passed unnoticed by the younger generations of researchers; we contrast and discuss both the latest and early contributions of this field, as well as highlighting several unsettled topics that should be revisited to improve our understanding of the ACP and HCA structures and in vitro/in vivo formation mechanisms.