Title: Biomineralization Of White Spot Dental Enamel Lesions Via A Protein-based Approach ‘‘KERATINAMEL’’
Funder: The Academy of Medical Sciences

Abstract: The overarching aim of this proposal is to develop novel clinically friendly protein-based approaches to treat white spot dental enamel lesions (WSLs). We will exploit the infiltration of keratins as models of intrinsically disordered protein (IDPs) frameworks within the porous enamel white spot lesions, to trigger the initial crystal nucleation in-situ within the defect, and further guide the crystal growth of enamel-like tissues. Dental caries is the most prevalent chronic disease worldwide that affects dental hard tissues, accounting for almost half of all tooth extractions, therefore remains a major public health problem. It affects both primary and permanent teeth. It ranges from mild white spot lesions (WSL) to severe loss of tooth structure, requiring extensive restorative treatment. Amelogenin, an intrinsically disordered protein (IDP), is the major extracellular protein in developing enamel and is thought to be critical for the formation of the hierarchical architecture of enamel. In this proposal, we aim to exploit keratins as models of IDPs to develop clinically-friendly approaches to treat (WSL). In order to achieve this, we will a) optimise keratin extraction from natural waste tissues, b) develop chemical and photo- crosslinking approaches specific for keratins to optimise their protein disorder-order synergism, c) infiltrate WSL in situ, and hierarchically mineralise the keratins scaffolds into enamel-like structures. This will allow us to develop the first-in-field generation of protein-based dental materials that have the potential to recreate not the chemistry of the native dental enamel, but also its well-known hierarchical structure.

Lay abstract: Dental caries known as 'dental decay' is the most prevalent disease worldwide that affects teeth, accounting for almost half of all teeth being pulled out, therefore remains a major public health problem. It affects both baby and adult teeth. It ranges from early small white spot lesions (WSL) within dental enamel 'the outer layer of our teeth' to severe loss of tooth structure beyond enamel, which requires extensive dental treatment. At present, the materials of choice to replace lost enamel are the non-aesthetic ‘silver’ restoration (amalgam) mercury-rich metal alloys materials and composite resins. Amalgam restorations do not adhere to tooth structures, providing only a mechanical interface between the material and the remaining tooth structure. While, composite resin material, has limited longevity and tends to require replacement after a few years, which leads to a phase known as ‘replacement cycle’ that consists of replacing older fillings with new ones, further causing tissue destruction and ultimately tooth loss. The overarching aim of this proposal is to develop novel clinically friendly protein-based approaches to treat early dental decay. We will exploit the infiltration of sheep's wool keratins as a building block to infiltrate the porous enamel white spot lesions, to trigger their healing into the 'like-by-like' to optmise longevity of the treatments. This will allow us to develop the first-in-field generation of protein-based dental materials that have the potential to recreate not the chemistry of the native dental enamel, but also its well-known hierarchical structure.

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL