Use of bioactive materials in caries management

Abstract

Dental caries is a widely recognised non-communicable chronic disease influenced by behaviour and cariogenic biofilm. It can be identified, diagnosed, and managed using biological approaches. The concept of minimal intervention dentistry and non-restorative strategies has been developed based on these biological principles. Non-restorative management aims to detect caries lesions early and minimize the loss of healthy tooth structure. Bioactive materials are important in promoting minimal intervention dentistry and non-restorative strategies. This thesis includes six components to explore the development of bioactive materials in dental caries treatment. The first part is a literature review summarising the available evidence on the outcomes of current bioactive materials in managing dental caries. Common bioactive materials for caries management include fluoride, calcium- and phosphate-based materials, graphene-based materials, metal-oxide nanomaterials, and peptide-based materials. Among these bioactive materials, antimicrobial peptides have attracted significant research interest recently. Natural antimicrobial peptides in oral cavities are the first line of defence against oral pathogenic microbes, such as Streptococcus mutans and Candida albicans. A bibliometric analysis was performed to explore and quantify the global research interest in antimicrobial peptides for caries management. This study included 163 publications, consisting of 115 laboratory studies (71%), 29 clinical trials (18%), and 19 reviews (11%). This analysis identified an increasing trend in global interest in antimicrobial peptides for caries management since 2002. Because natural antimicrobial peptides are unstable in the oral environment, researchers are working to develop novel synthetic antimicrobial peptides with improved stability and antimicrobial activities to aid in caries management. We conducted a systematic review to investigate the methods of creating novel peptides for caries management. This review analysed 62 studies, most of them were rated as medium risk of bias. Forty-seven studies reported 57 antimicrobial peptides, and ten studies reported mineralising peptides. The two most common methods for developing peptides for caries management used in these studies were the template-based design method and the conjugation method. Based on the template-based design and conjugation methods, we developed a novel anti-caries peptide Gallic acid-Polyphemusin-I (GAPI) by fusing Gallic acid (GA) with Polyphemusin-I (PI). Our study showed that GAPI demonstrated good biocompatibility and stability in human saliva. We developed a multi-species cariogenic biofilm and then found that GAPI had anti-biofilm capabilities. We used a chemical pH cycling model to confirm the mineralising properties of GAPI. In addition, we tested the antibacterial effects of GAPI on common oral pathogens. The results showed GAPI had potential for managing oral infections. Further in vitro study using biochemical model was performed to confirm the remineralising effects of GAPI on dentine caries. This unique model incorporates both biological and chemical factors to create pH changes and establish a microbiological environment that mimics the bacterial impact in the oral cavity. Artificial dentine carious lesions were created using S. mutans biofilm. This in vitro study demonstrated the anti-biofilm and remineralising effects of GAPI on S. mutans biofilm and artificial caries. In the future, additional in vivo studies using animal models should be undertaken to confirm the validity of the anti-caries peptide GAPI.