A Dentin Biomimetic Remineralization Material with an Ability to Stabilize Collagen.

Abstract

The integrity of collagen matrix structure is a prerequisite for effectively inducing biomimetic remineralization. Repeated low pH stimulation activates matrix metalloproteinases (MMPs) in dental caries. Activated MMPs cause the breakdown of collagen fibrils. Collagen stabilization is a major obstacle to the clinical application of remineralization templates. Here, galardin-loaded poly(amido amine) (PAMAM)-NGV (PAMAM-NGV@galardin, PNG) is constructed to induce collagen stabilization and dentin biomimetic remineralization simultaneously, in order to combat early caries in dentin. PAMAM acts in the role of nucleation template for dentin remineralization, while galardin acts as the role of MMPs inhibitor. NGV peptides modified on the surface of dendrimer core can form small clusters with synergistic movement in short range, and those short-range clusters can form domain areas with different properties on the surface of PAMAM core and restrict the movement of collagen, favoring collagen crosslinking, which can be explained through the computational simulation analysis results. NGV peptides and galardin show a dual collagen-protective effect, laying the foundation for the dentin remineralization effect induced by PAMAM. PNG induces dentin remineralization in an environment with collagenase, meanwhile showsing anti-dentin caries efficacy in vivo. These findings indicate that PNG has great potential to combat early dentin caries for future clinical application.