Biomimetic remineralisation of hydroxyapatite on human enamel and dentine

Abstract

Dental enamel is the highly mineralised tissue made up of approximately 95% hydroxyapatite. As the outermost layer of teeth, enamel is susceptible to caries due to the products of bacteria metabolism; or can be lost by trauma or by non-carious tooth loss resulting from dental erosion, attrition, abrasion or acidic foods. As the enamel lesions progress into dentine, tooth hypersensitivity often develops when the exposed dentine is subjected to stimuli. Traditional treatments include replacing the defected tooth structure with dental restorative materials such as amalgam, composite resin, and ceramics. However, marginal leakage, hypersensitivity and secondary caries often happens at the interface. Therefore, there is a need for scientists to design an alternative strategy to repair the tooth lesions. Biomineralisation process is an organic matrix-mediated non-classical crystallization pathway. Biomimetic mineralisation is concepts from biomineralisation trying to transfer biomineralisation principles to the regeneration of new biomaterials. This study systematically reviewed the laboratory methods on biomimetic mineralisation of demineralised human enamel and dentine, respectively. Many studies reported success in biomimetic mineralisation of enamel and dentine. However, there still exist some problems in the biomimetic mineralisation of enamel and dentine, such as remineralisation conducted under non-physiological conditions, potential contamination in natural protein-guided mineralisation, and the difficulties in reproducing the structural hierarchy of apatite deposition within the collagen matrix. Thus, we aimed to remineralise the demineralised enamel and dentine using biomimetic mineralisation methods. Firstly, we constructed an agarose hydrogel biomimetic mineralisation model to mimic the gel-like microenvironment of initial enamel formation. The tissue generated in this model had enamel prism-like layers containing well-defined hexagonal hydroxyapatite crystals. The modulus of elasticity and the nanohardness of the regenerated enamel prism-like tissue were similar to those of natural enamel. Based on this study, a follow-up study was designed by adding enamel matrix derivative in this agarose hydrogel biomimetic mineralisation model to mimic the organic matrix protein in guiding the formation of enamel prism-like tissue. Enamel matrix derivative promoted in vitro biomimetic mineralisation and facilitated enamel prism-like tissue formation on demineralised human enamel. The regeneration of enamel using this model is a promising approach for the management of enamel loss. Secondly, casein phosphopeptide-amorphous calcium phosphate was applied to the phosphorylated dentine surface to induce the biomimetic mineralisation of dentine collagen fibrils. Casein phosphopeptide-amorphous calcium phosphate could induce intrafibrillar and interfibrillar apatite crystals nucleation and growth along the phosphorylated dentine collagen fibres. We also successfully designed and fabricated a novel oligopeptide to mimic the functions of non-collagenous proteins in the biomineralisation process of dentine. Crystals were observed covering the oligopeptide-coated dentine surface, within the demineralised dentine collagen matrix and occluding dentinal tubules. This oligopeptide can induce biomimetic mineralisation of dentine. Therefore, we concluded that biomimetic mineralisation of enamel and dentine is a potential therapeutic technique for the management of tooth lesions. However, there are still challenges in biomimetic mineralisation, such as the influence of pellicle and biofilm and the need of proof-of-concept. The next step is to transfer the strategies for future clinical applications to benefit patients.