Cyclic silicate active site and stereochemical match for apatite nucleation on pseudowollastonite bioceramic–bone interfaces

Hydroxyapatite (Ca5(PO4)3(OH)) forms on pseudowollastonite (psW) (α-CaSiO3) in vitro in simulated body fluid, human parotid saliva and cell-culture medium, and in vivo in implanted rat tibias. We used crystallographic constraints with ab initio molecular orbital calculations to identify the active site and reaction mechanism for heterogeneous nucleation of the earliest calcium phosphate oligomer/phase. The active site is the planar, cyclic, silicate trimer (Si3O9) on the (0 0 1) face of psW. The trimer has three silanol groups (>SiOH) arranged at 60° from each other, providing a stereochemical match for O atoms bonded to Ca2+ on the (0 0 1) face of hydroxyapatite. Calcium phosphate nucleation is modeled in steps as hydrolysis of surface Ca–O bonds with leaching of Ca2+ into solution, protonation of the surface Si–O groups to form silanols, calcium sorption as an inner-sphere surface complex and, attachment of HPO42−. Our model explains the experimental solution and high resolution transmission electron microscopy data for epitaxial hydroxyapatite growth on psW in vitro and in vivo. We propose that the cyclic silicate trimer is the universal active site for heterogeneous, stereochemically promoted nucleation on silicate-based bioactive ceramics. A critical active site-density and a point of zero charge of the bioceramic less than physiological pH are required for bioactivity.