Natural Materials' Potential as Alternative Teeth Remineralization Agents: A Scoping Review

Abstract Dental caries is one of the world's major oral health issues. According to The Burden of Disease Study (2016), almost half of the world's population suffers oral health issues, particularly dental caries (3.58 billion individuals). Dental caries treatment through teeth remineralization can be conducted naturally or using remineralization agents. The aim of this study was to map the scientific evidence of natural materials' potential as teeth remineralization agents. The method utilized in this study was the scoping review following the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review, that is, article searching using search strategies, article screening, data extraction, and conclusion constructing. The searching process was through PubMed, EBSCOhost, and ScienceDirect using keywords and following the inclusion and exclusion criteria. Twenty articles were found and further analyzed. All articles provided the natural materials' potencies in the perspective of antibacterial, increasing saliva pH, remineralization ability, and increasing the hardness of teeth surface. It can be concluded that natural materials can potentially be alternative teeth remineralization agents.


Introduction
The Global Burden of Disease Study in 2016 stated that oral diseases, dental caries in particular, are suffered by almost half of the people worldwide (AE3.58 billion people).The result of Basic Health Research (Riset Kesehatan Dasar/Riskesdas) in 2018 also reported that dental caries/pain/defects were the most common oral disease in Indonesia (45.3%). 1 Dental caries is a multifactorial chronic disease related to the instability of biofilm due to the fermentation of carbohydrates (glucose, fructose, sucrose, and maltose) by specific microorganisms (Streptococcus mutans and Lactobacillus) and the dynamical condition of the demineralization and the remineralization of the teeth's hard tissue. 2,3ries is a disease associated with an acid-producing biofilm that starts the teeth demineralization process. 4The teeth demineralization process is a prolonged instability between pathological and protective factors, thereby leading to the dissolution of apatite crystals in teeth and the deprivation of calcium, phosphate, and other ions.The body's natural reaction toward dental caries is teeth remineralization, which will restore the calcium and phosphate ions supplied from sources outside the body to induce ion deposition to the crystallites on demineralized email. 5o date, teeth remineralization agents are readily available in the market, for example, casein phosphopeptideamorphous calcium phosphate (CPP-ACP), fluor, and nanohydroxyapatite.However, these materials have shortcomings regarding their expensive cost for the lower-middle class economy. 6Nano-hydroxyapatite as a teeth remineralization agent requires further study to verify its remineralization properties. 7Other alternative remineralization agents that have been researched as the substitute for chemical materials are natural materials, for example, Aloe vera, Galla chinensis, siwak (Salvadora persica), chocolate (Theobroma cacao), bilimbi (Averrhoa bilimbi), blood clam shells (Anadara granosa), soybean (Glycine max Merrill), rice (Oryza sativa), and others.Natural materials such as teeth remineralization agents are assumed to have similar potential vis-à-vis the existing teeth remineralization with a more affordable cost. 6The selection of natural materials in this study was based on the number of articles found and suitable to the determined criteria.Based on the explanation above, it is essential to conduct a study about the potential of natural materials as alternative teeth remineralization agents.

Method
This present study was a scoping review, a knowledge synthetization following a systematical approach in the evidence-mapping of a topic and identifying the primary concept, sources, and theories. 8The study began with searching articles on the databases, determining the inclusion and exclusion criteria according to population, concept, and context, performing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR) procedures, and extracting the data. 9The article searching was conducted on three databases, that is, PubMed, EBSCOhost, and ScienceDirect, as seen in ►Table 1.
The procedure used the search strategies using AND as the Boolean operators and keywords.The keywords used were: aloe vera AND dentistry, averrhoa bilimbi AND dentistry, galla chinensis AND dentistry, theobroma cacao AND dentistry, salvadora persica AND dentistry.The searching used the filter feature for the year publication of 2013-2023.The article determination was based on the inclusion and exclusion criteria provided in ►Table 2.
The article selection was conducted through the screening, eligibility, and stages according to the PRISMA-ScR flowchart, represented in ►Fig. 1.
The article selection began with duplicate checking, title or abstract screening, and full-text article screening.The number of articles found from three databases was 569 (263 articles from PubMed, 130 articles from EBSCOhost, and 176 articles from ScienceDirect), and added with 7 articles that were found from hand searching.The total number of articles screened for duplicate checking was 576.After duplicate checking, 100 articles were excluded.The number of articles screened for title or abstract screening was 476.After title or abstract screening, 440 articles were excluded.The 36 remaining articles were read in full text to determine the articles for further analysis.Sixteen articles were excluded, and 20 articles were selected for further analysis.
Further into the analysis, this study demonstrates the potentials that natural materials, for example, Aloe vera, Averrhoa bilimbi, Galla chinensis, Salvadora persica, and Theobroma cacao, can provide the environment which supports remineralization process to occur.Conditions that were being tested included antimicrobial activity,

Results
The article screening procedure resulted in 20 included articles for further analysis.The articles were analyzed and transcribed by authors' names, country, publication year, study design, study objectives, type of natural materials, and conclusion (►Table 3).The included articles consist of five articles about Aloe vera, three about Averrhoa bilimbi, four about Galla chinensis, four about Salvadora persica, and four about Theobroma cacao.The natural materials were tested using different study designs, dosage forms, and concentrations to discover their potential in aiding teeth remineralization.The discussion in the table involves the capabilities of each natural material in the teeth remineralization process, that is, antibacterial properties, remineralization ability, increasing saliva pH, and increasing the hardness of teeth surfaces.

Discussion
Natural materials are potentially teeth remineralization agents in various perspectives, for example, antimicrobial properties, remineralization ability, increasing saliva pH, and increasing the hardness of teeth surface.All articles included in this study reported natural materials' potencies in sup-porting teeth remineralization.The analysis results provided information that natural materials (Aloe vera, Averrhoa bilimbi, Galla chinensis, Salvadora persica, and Theobroma cacao) could be used as alternative teeth remineralization agents.
1][12][13][14] Yikici and Ozcan stated that Aloe vera intensified the remineralization efficiency of toothpaste in demineralized enamel.Their study show that lesser active components can be found in commercially available toothpaste through processing, therefore making Aloe vera gel when applied directly better in aiding remineralization. 14Al Haddad et al reported that the teeth remineralization outcomes from Aloe vera gel, fluoride toothpaste, and Aloe vera/fluoride toothpaste did not differ much.Polyphenols in Aloe vera gel is likely to be the active components making the gel acts as a dental remineralizing booster. 12Aloe vera was also discovered to possess antibacterial effects against oral pathogen bacteria in a study by Jain et al and subsequently supported by studies by Hajiahmadi et al and Al Haddad et al, which reported that Aloe vera inhibited the growth of Streptococcus mutans and Lactobacillus-oral pathogen bacteria. 10,12,13Hajiahmadi et al also mentioned that propolis and Aloe vera gel yielded better antibacterial effects vis-à-vis CPP-ACP. 10 According to Bhati et al, Aloe vera could be an alternative to fluoride toothpaste in terms of antimicrobial properties.Natural Materials' Potential as Alternative Teeth Remineralization Agents Irmaleny et al.
6][17] According to Abidin and Nainggolan, Averrhoa bilimbi extract yielded significant effects in the enamel remineralization and produced an enamel layer with smaller porous in demineralized teeth.The study also reported that the combination of Averrhoa bilimbi extract and CPP-ACP induced enamel remineralization closer to normal conditions.Abidin and Nainggolan provided that H þ ion in Averrhoa bilimbi extract when applied will bind into HPO 4 2À in saliva and furthermore binds with Ca 2þ from the extract will produce CaHPO 4 as a result that will diffuse into the teeth surface enhancing the remineralization process. 15Fadel et al stated that Averrhoa bilimbi extract could suppress the growth of Streptococcus mutans, which is the causative agent of dental caries. 17Based on a study by Restuning et al, the bilimbi leaves boiled water could also increase saliva pH (6.73). 169][20][21] Zhang et al stated that the chemical components of Galla chinensis could induce enamel caries remineralization in rats.Remineralization that Galla Chinensis provides are different than fluoride because enamel organic matrix plays a decent role in assisting the process as they will make a large complex becoming calcium ion carrier. 19Abdel-Azem et al, in their study, added the fact that Galla chinensis possessed remineralization ability on dentin lesions.Component contained within Galla chinensis extract from the complex "dentin organic matrix -Galla Chinensis Extract -Ca 2þ " can diffuse into dentin lesions providing remineralization as it delivers Ca 2þ ions and helps in mineral ions deposition into the surface.Their study also compared Galla chinensis and NaF, and it was discovered that Galla chinensis possessed remineralization ability after 1 minute of soaking. 18A study by Kim and Jin reported that Galla chinensis significantly increased enamel remineralization, led to bactericidal activity against Streptococcus mutans, and could maintain a pH level of 7. 20 Tang et al pointed out that one of the chemical components of Galla chinensis was gallic acid, which attributed in the hydroxyapatite-resembling crystal formation after 3 days of application. 21iwak (Salvadora persica) could be used as a teeth remineralization agent due to its remineralization ability and antibacterial effect. 11,22-24A study by Bhati et al stated that Salvadora persica can be used as a substitute for fluoride toothpaste due to its antibacterial properties. 11Balto et al and Abhary and Al-Hazmi also reported that the antimicrobial property of Salvadora persica was effective against various oral pathogens and was classified as a broad-spectrum antimicrobial.Additionally, Balto et al stated that active components such as isothiocyanates provide antibacterial property which results in a better environment on the oral space.The study that Abhary and Al-Hazmi conducted using Salvadora persica in preparation as a mouth wash supports the antimicrobial activity that contains in it. 22,247][28] Fajriani et al mentioned that Theobroma cacao extract could reduce the amount of Streptococcus mutans colonies in children. 28According to Irmaleny et al, Theobroma cacao could increase the hardness of enamel microstructure, supported by a study by Pribadi et al that compared cacao extract with fluoride.Additionally, Irmaleny et al stated that direct application of theobromine inside the cocoa extract will form interstitial reaction to substitute the loss of hydroxyapatite crystal, which in other words can describe the remineralization process that it can provide. 26,27Yuanita et al, in their study, stated that Theobroma cacao gel was better at strengthening the enamel visà-vis CPP-ACP. 6The usage of Theobroma cacao resulted in an increase in enamel hardness by up to 40%. 6][31] The limitation of this scoping review involves the heterogeneous articles regarding the samples, the study designs, and the results due to the inclusion and exclusion criteria.Therefore, further study is required to analyze natural materials' type, dosage form, and effectiveness.Nevertheless, the natural materials selected in this study can be the scientific evidence of natural materials being alternatives for teeth remineralization agents.

Conclusion
Natural materials are potentially utilized as dental mineralization agents due to their properties in presenting an antibacterial effect, increasing saliva pH, and increasing the hardness of enamel layer.

Fig. 1
Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR) flowchart.

Table 1
Searching process in databases using keywords

Table 3
Potentials of natural materials as teeth remineralization agents European Journal of Dentistry © 2023.The Author(s).Natural Materials' Potential as Alternative Teeth Remineralization Agents Irmaleny et al.

Table 3 (
Continued) European Journal of Dentistry © 2023.The Author(s).Natural Materials' Potential as Alternative Teeth Remineralization Agents Irmaleny et al.

Table 3 (
Continued) Natural Materials' Potential as Alternative Teeth Remineralization Agents Irmaleny et al. from studies by Sabbagh et al and Balhaddad et al also mentioned that Salvadora persica possessed antimicrobial properties, particularly against Streptococcus mutans. 23,25 Abbreviations: CPP-ACP, casein phosphopeptide-amorphous calcium phosphate; EDX, energy-dispersive X-ray spectroscopy; SEM, scanning electron microscopy.European Journal of Dentistry © 2023.The Author(s).