Hyaluronic acid-mediated collagen intrafibrillar mineralization and enhancement of dentin remineralization

Non-collagenous proteins (NCPs) in the extracellular matrix (ECM) of bone and dentin are known to play a critical regulatory role in the induction of collagen fibril mineralization and are embedded in hyaluronic acid (HA), which acts as a water-retaining glycosaminoglycan and provides necessary biochemical and biomechanical cues. Our previous study demonstrated that HA could regulate the mineralization degree and mechanical properties of collagen fibrils, yet its kinetics dynamic mechanism on mineralization is under debate. Here, we further investigated the role of HA on collagen fibril mineralization and the possible mechanism. The HA modification can significantly promote intrafibrillar collagen mineralization by reducing the electronegativity of the collagen surface to enhance calcium ions (Ca2+) binding capacity to create a local higher supersaturation. In addition, the HA also provides additional nucleation sites and shortens the induction time of amorphous calcium phosphate (ACP)-mediated hydroxyapatite (HAP) crystallization, which benefits mineralization. The acceleration effect of HA on intrafibrillar collagen mineralization is also confirmed in collagen hydrogel and in vitro dentin remineralization. These findings offer a physicochemical view of the regulation effect of carbohydrate polymers in the body on biomineralization, the fine prospect for an ideal biomaterial to repair collagen-mineralized tissues.