Modification of collagen with proanthocyanidins by mimicking the bridging role of glycosaminoglycans for dentine remineralization

Glycosaminoglycans (GAGs) form bridging cross-bands that maintain structural integrity of collagen in the organic matrix of dentine. In dentine caries, proteolytic enzymes appeared to trigger GAGs bridge degradation, followed by breakdown of the collagen network, imposing critical limitations on dentine remineralization via biomimetic mineralization of collagen. While contemporary mechanisms of collagen modification through immobilizing functional groups have been established to improve collagen mineralization, this effort remains a challenge due to lack of consideration in preserving the spatial stability of collagen. In our study, proanthocyanidins (PA) was applied to simulate the bioactivities of GAGs. Detailed analyses showed that PA reconstructed interfibrillar bridges of collapsed collagen network and reduced interfacial energy between mineral-organic phases to enhance collagen hydrophilicity, subsequently facilitating infiltration of calcium phosphate precursors and hence promoting collagen mineralization. With this strategy, mechanical behaviors of demineralized dentine were significantly improved. PA exhibited satisfactory inhibitory effects on the activity of cariogenic bacteria (comparable to that of chlorhexidine). Moreover, ex vivo study indicated that remineralization and antibacterial effects were evident in the rat oral cavity. This strategy highlights the importance of maintaining structural integrity of the collagen network in dentine remineralization and offers great clinical potential for the effective treatment of dentine caries.