The glycerol stabilized calcium phosphate cluster for rapid remineralization of tooth enamel by a water-triggered transformation

Using remineralization materials to grow hydroxyapatite (HAP) crystals on the surfaces is a common strategy for the repair of early demineralized tooth enamels. As the efficacy is often impaired by harsh dynamic oral environments, e.g., continuous flow of saliva and friction of moving maxillofacial muscles, a rapid remineralization is expected to avoid or diminish these influences. But there has been a great dilemma to address this expectation, as the stabilizers used for preparation and storage of these materials, in turn, could resist their transformation during remineralization. Here, by dissolving the ions of calcium and phosphate in mixed solvents of glycerol and water, we found a stable species with ultrasmall size (1-2 nm), termed glycerol stabilized calcium phosphate cluster (GCPC), which can perform a fast enamel repair via the water-triggered transformation in both static or dynamic environments. The high permeability and water-responsive character allow GCPC to easily enter the nano-/micro-sized enamel defect sites and transform into HAP nanorods immediately, going through a special intermediate—amorphous calcium phosphate nanowire, whose subsequent crystallization product (the nanorods) stands vertically to them and enamel surface. Both in vitro and in vivo studies display that, GCPC forms a compact HAP repair layer within a short time (30 min), which is much faster than the conventional materials (hours or days), and recovers mechanical properties to the values close to those of sound enamel. Moreover, a double-blind, randomized, crossover clinical trial based on in situ model further demonstrates an excellent remineralization efficiency of GCPC in the real human oral environment. Given its rapid repair capacity, simple preparation process, low cost and remarkable biocompatibility, GCPC is promising for large-scale preparation and clinical applications in dental remineralization.