Biomimetic chondroitin sulfate synergized with polyzwitterion system induced collagen matrix remineralization for dentin hypersensitivity

Dentin hypersensitivity is a globally oral dilemma arising from the exposure of dentinal tubules (DTs), which elicits discomfort upon external stimulation. Due to the complex dentin structure and oral environment, developing a multifunctional repair strategy that combines dentin remineralization, antibacterial properties, and DT occlusion remains highly challenging. Herein, we propose a biomimetic remineralization approach utilizing glycosaminoglycan chondroitin sulfate (CS) to mimic the bioactivity of proteoglycans (GAGs) for modifying collagen fibrils, in conjunction with a zwitterionic poly(carboxybetaine acrylamide) (PCBAA) to stabilize amorphous calcium phosphate (ACP), CS modification not only increases the negative charge density on the collagen but also provides additional nucleation sites, facilitating the binding of calcium phosphate precursors and thereby promoting collagen mineralization. Both in vitro and in vivo experiments demonstrate that the CS-based biomimetic mineralization strategy achieves dense occlusion of DTs and effective remineralization of demineralized dentin. The remineralized dentin exhibits significant antibacterial activity against cariogenic bacteria (e.g., Streptococcus mutans and Lactobacillus acidophilus ), and its mechanical properties can be restored to level comparable to that of sound dentin. Thus, this strategy integrates three key functions, dentin matrix remineralization, effective tubular occlusion, and antibacterial surface modification, offering substantial clinical potential for the effective treatment of dentin hypersensitivity.