Next Article in Journal
Diversity of Biogenic Nanoparticles Obtained by the Fungi-Mediated Synthesis: A Review
Next Article in Special Issue
Investigation of the Wetting Properties of Thalassemia Patients’ Blood Samples on Grade 5 Titanium Implant Surfaces: A Pilot Study
Previous Article in Journal
Effect of Segment Types on Characterization of Soft Sensing Textile Actuators for Soft Wearable Robots
Previous Article in Special Issue
Cell Type-Specific Effects of Implant Provisional Restoration Materials on the Growth and Function of Human Fibroblasts and Osteoblasts
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomimetics
Volume 7
Issue 4
10.3390/biomimetics7040250
biomimetics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Overview on Adjunct Ingredients Used in Hydroxyapatite-Based Oral Care Products

by
Joachim Enax
1,*,
Bennett T. Amaechi
2,
Erik Schulze zur Wiesche
1 and
Frederic Meyer
1,*
1
Research Department, Dr. Kurt Wolff GmbH & Co. KG, Johanneswerkstr. 34 36, 33611 Bielefeld, Germany
2
Department of Comprehensive Dentistry, School of Dentistry, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
*
Authors to whom correspondence should be addressed.
Biomimetics 2022, 7(4), 250; https://doi.org/10.3390/biomimetics7040250
Submission received: 30 November 2022 / Revised: 14 December 2022 / Accepted: 15 December 2022 / Published: 19 December 2022
(This article belongs to the Special Issue Biomimetic Approach to Dental Implants)
Browse Figure
Versions Notes

Abstract

:
Hydroxyapatite, Ca5(PO4)3(OH), is a biomimetic active ingredient, which is used in commercial oral care products such as toothpastes and mouthwashes worldwide. Clinical studies (in vivo) as well as in situ and in vitro studies have shown the preventive effects of hydroxyapatite in various field of oral care. In some products, hydroxyapatite is combined with other active ingredients, to achieve an additional antibacterial effect or to promote gum health. This review analyzes the efficacy of six selected natural and nature-inspired ingredients that are commonly used together with hydroxyapatite. These additional actives are either antibacterial (lactoferrin, xylitol, and zinc) or promote gum health (allantoin, bisabolol, and hyaluronic acid). A systematic literature search was performed, and all studies found on each ingredient were analyzed. In summary, all analyzed ingredients mentioned in this review are well described in scientific studies on their beneficial effect for oral health and can be used to expand the preventive effect of hydroxyapatite in oral care products.

1. Introduction

Oral care products such as toothpastes and mouthwashes are used to prevent oral diseases such as caries and gingivitis [1,2]. They usually contain various ingredients, such as remineralizing agents, antibacterial agents, abrasives, thickeners, humectants, preservatives, surfactants, and flavors [1]. Other ingredients can be added for sensitivity relief or tooth whitening [1,3,4,5].
In recent years, the use of biomimetic ingredients in oral care has become more relevant [6,7,8,9]. An example of a globally used biomimetic ingredient in oral care products is particulate hydroxyapatite, Ca5(PO4)3(OH), a synthetic calcium phosphate mineral that is inspired by the natural enamel crystallites [10,11]. Hydroxyapatite shows good biocompatibility when used in oral care products, and it is also used as a food additive [12,13]. Various studies have shown its efficacy in different areas, such as caries prevention and the reduction of dentin hypersensitivity. The preventive effects of hydroxyapatite used in oral care products have already been published extensively [7,14,15,16,17,18].
In oral care products, hydroxyapatite can be used as a sole active ingredient [19] (in toothpastes besides other “excipients” such as abrasives, surfactants, etc.) or can be combined with other natural or nature-inspired ingredients, e.g., antibacterial ingredients and ingredients for gum care, with the goal to provide safe and efficient oral care formulations for all age groups.
The aim of this review is to present and discuss studies analyzing the efficacy of six selected ingredients functioning either as antibacterial (lactoferrin, xylitol, and zinc) or caring/moisturizing agents (allantoin, bisabolol, and hyaluronic acid) that are used as adjunct ingredients in commercial hydroxyapatite-based oral care products.

2. Literature Search

Six adjunct ingredients that are used in hydroxyapatite-based oral care products (e.g., in Karex and Bioniq®, Dr. Kurt Wolff GmbH and Co. KG, Bielefeld, Germany) were selected based on their antibacterial or caring/moisturizing properties for this review. Note that some of the analyzed ingredients are also used as hydroxyapatite adjuncts in oral care products of other brands/companies.
The literature search was carried out using PubMed. The following search terms were used to identify the relevant studies:
“X AND (toothpaste OR dentifrice OR mouthwash OR mouth rinse)”, with X = lactoferrin, xylitol, zinc, allantoin, bisabolol, and hyaluronic acid OR hyaluronate (note that hyaluronate, e.g., sodium hyaluronate, is the salt of hyaluronic acid). All results until 19 October 2022 were included in this review. For lactoferrin, allantoin, bisabolol, and hyaluronic acid/hyaluronate, all abstracts were screened. Because of the high number of results for xylitol and zinc (Table 1), only the most recently published review articles of these two ingredients were screened; additionally, we refer to literature reviews/textbooks. For the search and screening of studies in oral care for lactoferrin, allantoin, bisabolol, and hyaluronic acid/hyaluronate, the following exclusion criteria were applied: not in the scope of this review (e.g., studies performed not in the field of oral care/dentistry or studies where the focus was not on the respective active ingredient searched), review articles, articles in other languages than English, case reports, and animal studies. The most relevant studies analyzing the efficacy of the six mentioned ingredients in oral care products/formulations were selected and analyzed by the authors.

3. Overview on Adjunct Ingredients Used in Hydroxyapatite-Based Oral Care Products

The literature search showed that zinc was the ingredient with the highest number of results (2026), followed by xylitol (244) and hyaluronic acid/hyaluronate (52) (Table 1). Details on each ingredient will be presented below. The structural formulas of the ingredients are depicted in Figure 1.

3.1. Antibacterial Ingredients

3.1.1. Lactoferrin

Lactoferrin is an 80 kDa bilobal glycoprotein (connected by an α-helix), which can bind iron [21,22,23,24]. However, also different conformations of this protein exist that have ribonuclease-activity (cleaving RNA) but do not bind iron [25]. Binding iron leads to a confirmation-change from apolactoferrin to hololactoferrin [26]. Due to its iron-binding and RNase properties, lactoferrin shows antibacterial, antifungal, and antiviral properties [22,23,27]. Natural saliva contains approximately 8 µg mL−1 lactoferrin, and it can also be found in breast milk and tear fluid [28]. Lactoferrin for commercial use is usually isolated from bovine milk [22]. Human and bovine lactoferrin have been shown to have a high sequence-similarity with comparable antibacterial, antifungal, and antiviral properties [29].
Studies in oral care:
Lactoferrin is often used in oral care products in combination with other agents (e.g., other salivary enzymes such as lysozyme, or active oxygen), for an antibacterial effect, plaque reduction, and the prevention of gingivitis [23,30,31,32,33,34]. Lactoferrin-containing oral care products have been already successfully tested in children to reduce the levels of Streptococcus mutans in saliva [35]. Additionally, an in vitro study showed that lactoferrin reduces the attachment of early colonizers of the teeth, such as Streptococcus gordonii [36]. This helps to reduce bacterial biofilm-growth, thus preventing dental caries and gum diseases. Nagano-Takebe et al. showed that a lactoferrin layer can inhibit the initial bacterial colonization on titanium [37]. The authors concluded that covering implant-surfaces with lactoferrin can help to reduce periimplantitis. However, an in vitro study showed that a lactoferrin-containing toothpaste did not show superior antibacterial effects compared to a toothpaste containing the anionic surfactant sodium lauryl sulfate (SLS) [38]. In addition, Pizzo et al. could not find an inhibition of plaque regrowth by using a mouthwash with lactoferrin, lactoperoxidase, and lysozyme [39]. In patients with xerostomia, products with lactoferrin have been tested [40,41,42]. It is also part of some artificial saliva formulations [43]. An in situ/in vitro study by Jager et al. showed erosion-protective properties by using toothpaste with proteins (e.g., lactoferrin) [44]. For more information on lactoferrin in oral care, see reviews [27,28].

3.1.2. Xylitol

Xylitol, C5H12O5, is a sugar alcohol that most oral bacteria cannot metabolize (Figure 1) [45]. It can be isolated from birch and beech trees as well as from corncobs, and it is safe for children [46]. Different modes of actions of xylitol have been described, e.g., bacteriostatic action and a reduction of the acid production from sucrose in bacteria biofilms [45]. While most sugars (carbohydrates, Cx(H2O)y) can be metabolized by oral bacteria (glycolysis/fermentation) for energy-production (in form of adenosine triphosphate/ATP), this is not the case for xylitol. In brief, xylitol is actively taken up by oral bacteria, e.g., Streptococcus mutans, and this activates cellular mechanisms that should result in energy-production (ATP); however, most oral bacteria are not able to convert C-5-sugars to ATP at a level that is needed for cellular growth. Moreover, these cellular processes require energy, and the accumulation of C-5 sugars in bacteria cells inhibits glycolytic enzymes, leading to an energy-deficiency. Consequently, bacterial growth and acid production are inhibited, which is beneficial for caries prevention [47].
Xylitol is used not only in toothpastes and mouthwashes but also in products such as chewing gums and lozenges. Xylitol acts as a non-cariogenic sweetener in oral care products, where it stimulates salivary flow and increases the calcium and bicarbonate contents of saliva, thereby contributing indirectly to tooth remineralization and caries prevention. A recent meta-analysis shows the efficacy of xylitol in caries prevention, and xylitol was found to be more efficient than sorbitol and mannitol. It was concluded that the frequent use of xylitol is beneficial for oral health [48]. For more information on xylitol in oral care, see Limeback et al. and Fejerskov et al. [45,46].

3.1.3. Zinc

Zinc is an important trace element in the human body with many different functions (Figure 1) [49]. Zinc salts have been used as antibacterial ingredients in toothpastes and mouthwashes for a long time, and different zinc salts are used for this purpose, e.g., zinc citrate, zinc chloride, and zinc PCA (the zinc salt of l-pyrrolidone carboxylate [50]) [1,51].
Zinc salts are mainly used to reduce dental plaque, inhibit dental plaque formation, and prevent gingivitis and halitosis [52]. Additionally, zinc has calculus-preventing/-reducing properties, mainly because of its antibacterial properties [1,45]. Calculus reductions up to 50% have been shown using zinc-containing toothpastes [1]. Notably, it has been described that zinc salts (in contrast to other antibacterial agents, such as stannous salts and chlorhexidine) do not stain the tooth surface [53]. Zinc ions can also be incorporated into the apatite lattice (Zn2+ as substituent for Ca2+ [54]), forming a zinc hydroxyapatite that can be used as an active ingredient in oral care products [55]. Interestingly, zinc is occurs naturally in saliva and dental plaque [56].
Zinc can be taken up into bacterial cells, where it inhibits the glycolytic enzymes, thus inhibiting bacteria metabolism, which leads to reduced bacterial growth. Zinc is a component of saliva and of diet, and it exhibits high substantivity in the oral cavity [17]. For more information on zinc salts in oral care, see Brading et al. and Marsh et al. [53,57].

3.2. Ingredients for Gum Care

3.2.1. Allantoin

Allantoin, C4H6N4O3, is a heterocyclic organic molecule often used in skincare products, including products for babies (Figure 1) [58]. It can be synthesized, but there are also some natural sources (specific plants and food) [58]. Allantoin is used for different purposes, e.g., in oral care and skincare formulations [58]. Suzuki et al., have shown that allantoin can suppress the production of inflammatory cytokines by immune cells in human gingival fibroblasts in vitro. This helps to control inflammation in gingival cells [59].
Studies in oral care:
Magaz et al. showed that toothpastes and mouthwashes with allantoin, chlorhexidine, and dexpanthenol improved the periodontal disease index of patients with gingivitis [60]. A gel based on allantoin, chlorhexidine, and dexpanthenol improved wound healing [61]. Additionally, an allantoin-containing gel reduced postoperative pain and inflammation after tooth extraction [62]. Lopez-Lopez et al. demonstrated that an allantoin-containing gel is more effective in the reduction of pain and inflammation than a bicarbonate-based mouthwash after tooth extraction [63]. Allantoin was also found to influence cellular responses positively [64].

3.2.2. Bisabolol

α-(−)-bisabolol (hereafter denoted as bisabolol [65]) is an organic molecule (a sesquiterpene alcohol) and a natural component of chamomile oil (Matricaria spp.) (Figure 1) [65,66,67]. It has been shown that bisabolol is the predominant constituent of Matricaria chamomilla [68]. It can also be found in other plants, e.g., Eremanthus erythropappus and Smyrniopsis aucheri [65]. Bisabolol has anti-inflammatory, anti-irritant, and antibacterial effects and is used in numerous dermatological and cosmetic products [65,68].
Studies in oral care:
Amora-Silva et al. showed that a bisabolol-containing mouthwash improved wound healing and reduced pain after oral surgery, and it has been proposed to be an alternative to chlorhexidine to be used after oral surgeries [66]. Additionally, the reduction/prevention of oral mucositis in patients undergoing chemotherapy (radiation therapy and systemic chemotherapy) by a commercially available mouthwash based on chamomile has been reported [69]. Notably, no burning or unwanted effects were documented after the application of the mouthwash, which is an important characteristic for an oral care product for this patient group [69]. Additionally, in an in vitro study it was shown that a combination of bisabolol and tea tree oil has an antibacterial effect against Solobacterium moorei (clinical isolates), which is associated with halitosis. Forrer et al. tested different concentrations of bisabolol and its antibacterial effect on different halitosis-associated oral bacterial strains. They were able to show that bisabolol (in combination with tea oil) was able to reduce their growth-rate even at low concentrations [70].

3.2.3. Hyaluronic Acid

Hyaluronic acid, (C14H21NO11)n, is a glycosaminoglycan with various applications, e.g., in skin care (Figure 1) [71]. It is found not only on the skin but also in human saliva [72]. It acts as moisturizer by binding human cells and lubricating tissues [73].
Studies in oral care:
Hyaluronic acid and its salts (e.g., sodium hyaluronate) are used in oral care products, often in combinations with other ingredients (e.g., chlorhexidine), for plaque reduction and plaque control [74,75,76,77,78]. Several studies have shown that hyaluronic-acid-containing formulations can be used in the treatment and prevention of gingivitis/periodontitis [79,80]. For example, in combination with hydrogen peroxide, a hyaluronic-acid-containing mouthwash showed gingivitis-reducing effects [81]. Abdulkareem et al. showed that hyaluronic-acid-containing mouthwash was as effective as chlorhexidine in the reduction of gum bleeding; however, chlorhexidine showed a higher antibacterial effect than hyaluronic acid [82]. A mouthwash with hyaluronic acid and cetylpyridinium chloride was shown to be as effective as a chlorhexidine mouthwash in reducing plaque accumulation [83]. Furthermore, hyaluronic-acid-containing formulations reduced complications after tooth extractions [84,85]. However, Zorrilla et al. showed that the use of a chlorhexidine-chitosan gel resulted in better healing than with the use of a hyaluronic acid gel after oral surgery [86]. A mouthwash with hyaluronic acid, vitamin E, and triamcinolone acetonide can be used to treat oral mucositis [87]. This is in line with other studies on oral mucositis [88,89,90]. Other areas of application of hyaluronic-acid-containing formulations include the treatment of oral lichen planus [91,92,93], recurrent aphthous stomatitis [94], use in patients with implants [95], use in salivary substitutes [96], the reduction of symptoms after biopsy procedures [97,98], and use in denture-induced ulcerations [99]. Furthermore, Dong et al. described the use of antibacterial hyaluronic acid/chlorhexidine hydrogels [100].

3.3. Additional Ingredients

Hydroxyapatite can also be combined with other ingredients, e.g., with natural or nature-inspired substances [101], although the efficacy for some of them may be less documented in the literature. For example, a thorough in vitro screening of various alternative compounds regarding their antibacterial effect was published by Cieplik et al. [102].

4. Discussion

The biomimetic active ingredient hydroxyapatite is used in various fields of oral care [7,14,15,16,18,103]. It remineralizes early caries lesions [104,105,106,107], reduces the initial bacterial attachment to enamel similar to 0.2% chlorhexidine [19], and acts as buffer and a calcium and phosphate reservoir in biofilms [108]. To extend these preventive effects, hydroxyapatite can be used together with lactoferrin, xylitol, zinc, allantoin, bisabolol, and/or hyaluronic acid to achieve an antibacterial effect and to prevent/reduce gingivitis. In general, these combinations can be used in different oral care products (toothpaste, mouthwash, oral gel, etc.). However, each product has to be developed individually to avoid unintended interactions of the actives with other components of the formulation. Moreover, the stability, solubility, sensory properties, etc., of the actives in each product are important as well. The results of our search show that zinc salts have been described in more studies than the other analyzed active ingredients. A limiting factor in using, e.g., lactoferrin and hyaluronic acid in oral care products might be the relatively high price compared to “standard” ingredients of oral care products. Lactoferrin, zinc, allantoin, bisabolol, and hyaluronic acid are mainly used in oral care products for the prevention/treatment of periodontal diseases but also for other purposes (see above). Xylitol is mainly used to support caries prevention [46]. Xylitol is also used in chewing gums. It is important to mention that potential adjunct ingredients to hydroxyapatite are not limited to the ones discussed in this review because there are many other natural or natural-inspired active ingredients that can be used for various purposes [101,102]. A main goal in using such hydroxyapatite and adjunct ingredient(s) combinations in oral care is to provide safe and efficient alternatives to ingredients with potential side effects, such as tooth staining (chlorhexidine [109], stannous chloride/fluoride [110]), the risk of dental fluorosis in children (fluoride) [111], the potential risk of bacterial resistances (chlorhexidine) [112], or cytotoxic effects (cocamidopropyl betaine, sodium lauryl sulfate, and fluoride) [113]. Interestingly, the preventive spectrum of hydroxyapatite can be extended by the described adjunct ingredients (e.g., wound healing etc.; see above). Thus, various patient groups may benefit, for example, patients with periodontal diseases and patients with xerostomia.
This review has some limitations, which will be discussed hereinafter. It focuses on the search of studies analyzing the selected adjunct ingredients, and most tested formulations do not contain hydroxyapatite. There are, however, some studies analyzing formulations containing hydroxyapatite combinations (e.g., hydroxyapatite with lactoferrin [114], hydroxyapatite with xylitol [115,116,117], and hydroxyapatite with zinc (with zinc included in the apatite lattice [55] and zinc salts as an adjunct additive [8,116])). For example, Nocerino et al. studied the effect of hydroxyapatite particles functionalized with lactoferrin. They found the combination of hydroxyapatite and lactoferrin to be effective against different bacterial strains (gram-positive and gram-negative) but also to be more anti-inflammatory compared to lactoferrin alone [114]. Consequently, future studies should analyze potential synergistic effects of combined hydroxyapatite and known or novel adjunct ingredients. Another limitation is that many found that studies tested not only the efficiency of the sole ingredient but the effect of a whole formulation, e.g., hyaluronic acid with chlorhexidine [100], or lactoferrin with other salivary enzymes [40]. Note that hydroxyapatite itself has also been tested without any other ingredients, e.g., by Cieplik et al., and hydroxyapatite was shown to be a calcium and phosphate source and an acid buffer in bacterial biofilms in vitro [108]. Fabritius-Vilpoux et al. have shown the formation of mineral–mineral bridges between hydroxyapatite particles and enamel surfaces in vitro [11,118], and Kensche et al. studied the reduction of the initial bacterial colonization by hydroxyapatite in situ [19].

5. Conclusions

In conclusion, this review shows that there is good evidence that the reviewed adjunct ingredients, i.e., lactoferrin, xylitol, zinc, allantoin, bisabolol, and hyaluronic acid, can increase the oral disease preventive scope of hydroxyapatite-based oral care products.

Author Contributions

Concept development: all authors; literature search: all authors; and writing of the manuscript: all authors. All authors have read and agreed to the published version of the manuscript.

Funding

The work was supported by Dr. Kurt Wolff GmbH and Co. KG, Bielefeld, Germany.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

J.E., E.S.z.W., and F.M. are employees of Dr. Kurt Wolff GmbH and Co. KG, Bielefeld, Germany.

References

  1. Loveren, C.V. Toothpastes; Karger: Basel, Switzerland, 2013; Volume 23. [Google Scholar]
  2. Epple, M.; Enax, J. Moderne Zahnpflege aus chemischer Sicht. Chem. Unserer Zeit 2018, 52, 218–228. [Google Scholar] [CrossRef]
  3. Hu, M.L.; Zheng, G.; Lin, H.; Yang, M.; Zhang, Y.D.; Han, J.M. Network meta-analysis on the effect of desensitizing toothpastes on dentine hypersensitivity. J. Dent. 2019, 88, 103170. [Google Scholar] [CrossRef] [PubMed]
  4. Gillam, D.G. Dentine Hypersensitivity: Advances in Diagnosis, Management, and Treatment; Springer International Publishing: Berlin/Heidelberg, Germany, 2015. [Google Scholar]
  5. Epple, M.; Meyer, F.; Enax, J. A critical review of modern concepts for teeth whitening. Dent. J. 2019, 7, 79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Hannig, M.; Hannig, C. Nanomaterials in preventive dentistry. Nat. Nanotechnol. 2010, 5, 565–569. [Google Scholar] [CrossRef] [PubMed]
  7. Limeback, H.; Enax, J.; Meyer, F. Biomimetic hydroxyapatite and caries prevention: A systematic review and meta-analysis. Can. J. Dent. Hyg. 2021, 55, 148–159. [Google Scholar] [PubMed]
  8. Steinert, S.; Zwanzig, K.; Doenges, H.; Kuchenbecker, J.; Meyer, F.; Enax, J. Daily application of a toothpaste with biomimetic hydroxyapatite and its subjective impact on dentin hypersensitivity, tooth smoothness, tooth whitening, gum bleeding, and feeling of freshness. Biomimetics 2020, 5, 17. [Google Scholar] [CrossRef]
  9. Steinert, S.; Kuchenbecker, J.; Meyer, F.; Simader, B.; Zwanzig, K.; Enax, J. Whitening effects of a novel oral care gel with biomimetic hydroxyapatite: A 4-week observational pilot study. Biomimetics 2020, 5, 65. [Google Scholar] [CrossRef]
  10. Fabritius, H.-O.; Enax, J.; Meyer, F. Eine Reise ins Innere unserer Zähne. Titus-Verlag: Bielefeld, Germany, 2021. [Google Scholar]
  11. Fabritius-Vilpoux, K.; Enax, J.; Herbig, M.; Raabe, D.; Fabritius, H.-O. Quantitative affinity parameters of synthetic hydroxyapatite and enamel surfaces in vitro. Bioinspired Biomim. Nanobiomaterials 2019, 8, 141–153. [Google Scholar] [CrossRef] [Green Version]
  12. Epple, M. Review of potential health risks associated with nanoscopic calcium phosphate. Acta Biomater. 2018, 77, 1–14. [Google Scholar] [CrossRef]
  13. Enax, J.; Meyer, F.; Schulze zur Wiesche, E.; Epple, M. On the application of calcium phosphate micro- and nanoparticles as food additive. Nanomaterials 2022, 12, 4075. [Google Scholar] [CrossRef]
  14. O’Hagan-Wong, K.; Enax, J.; Meyer, F.; Ganss, B. The use of hydroxyapatite toothpaste to prevent dental caries. Odontology 2022, 110, 223–230. [Google Scholar] [CrossRef] [PubMed]
  15. Meyer, F.; Enax, J.; Amaechi, B.T.; Limeback, H.; Fabritius, H.-O.; Ganss, B.; Pawinska, M.; Paszynska, E. Hydroxyapatite as remineralization agent for children’s dental care. Front. Dent. Med. 2022, 3, 859560. [Google Scholar] [CrossRef]
  16. Enax, J.; Fabritius, H.-O.; Fabritius-Vilpoux, K.; Amaechi, B.T.; Meyer, F. Modes of action and clinical efficacy of particulate hydroxyapatite in preventive oral health care—state of the art. Open Dent. J. 2019, 13, 274–287. [Google Scholar] [CrossRef]
  17. Meyer, F.; Enax, J. Hydroxyapatite in oral biofilm management. Eur. J. Dent. 2019, 13, 287–290. [Google Scholar] [CrossRef] [Green Version]
  18. Izzetti, R.; Gennai, S.; Nisi, M.; Gulia, F.; Miceli, M.; Giuca, M.R. Clinical applications of nano-hydroxyapatite in dentistry. Appl. Sci. 2022, 12, 10762. [Google Scholar] [CrossRef]
  19. Kensche, A.; Holder, C.; Basche, S.; Tahan, N.; Hannig, C.; Hannig, M. Efficacy of a mouthrinse based on hydroxyapatite to reduce initial bacterial colonisation in situ. Arch. Oral Biol. 2017, 80, 18–26. [Google Scholar] [CrossRef]
  20. Wikipedia. Available online: en.wikipedia.org (accessed on 24 October 2022).
  21. Baker, E.N.; Baker, H.M. Molecular structure, binding properties and dynamics of lactoferrin. Cell. Mol. Life Sci. 2005, 62, 2531. [Google Scholar] [CrossRef]
  22. Wang, B.; Timilsena, Y.P.; Blanch, E.; Adhikari, B. Lactoferrin: Structure, function, denaturation and digestion. Crit. Rev. Food Sci. Nutr. 2019, 59, 580–596. [Google Scholar] [CrossRef]
  23. Tonguc-Altin, K.; Sandalli, N.; Duman, G.; Selvi-Kuvvetli, S.; Topcuoglu, N.; Kulekci, G. Development of novel formulations containing lysozyme and lactoferrin and evaluation of antibacterial effects on mutans streptococci and lactobacilli. Arch. Oral Biol. 2015, 60, 706–714. [Google Scholar] [CrossRef]
  24. Kell, D.B.; Heyden, E.L.; Pretorius, E. The biology of lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. Front. Immunol. 2020, 11, 1221. [Google Scholar] [CrossRef]
  25. Furmanski, P.; Li, Z.P.; Fortuna, M.B.; Swamy, C.V.; Das, M.R. Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity. J. Exp. Med. 1989, 170, 415–429. [Google Scholar] [CrossRef] [PubMed]
  26. Jameson, G.B.; Anderson, B.F.; Norris, G.E.; Thomas, D.H.; Baker, E.N. Structure of human apolactoferrin at 2.0 A resolution. Refinement and analysis of ligand-induced conformational change. Acta Crystallogr. D Biol. Crystallogr. 1998, 54, 1319–1335. [Google Scholar] [CrossRef] [PubMed]
  27. Krupińska, A.M.; Bogucki, Z. Clinical aspects of the use of lactoferrin in dentistry. J. Oral Biosci. 2021, 63, 129–133. [Google Scholar] [CrossRef] [PubMed]
  28. Berlutti, F.; Pilloni, A.; Pietropaoli, M.; Polimeni, A.; Valenti, P. Lactoferrin and oral diseases: Current status and perspective in periodontitis. Ann. Stomatol. 2011, 2, 10–18. [Google Scholar]
  29. Rosa, L.; Cutone, A.; Lepanto, M.S.; Paesano, R.; Valenti, P. Lactoferrin: A natural glycoprotein involved in iron and inflammatory homeostasis. Int. J. Mol. Sci. 2017, 18, 1985. [Google Scholar] [CrossRef] [PubMed]
  30. Hatti, S.; Ravindra, S.; Satpathy, A.; Kulkarni, R.D.; Parande, M.V. Biofilm inhibition and antimicrobial activity of a dentifrice containing salivary substitutes. Int. J. Dent. Hyg. 2007, 5, 218–224. [Google Scholar] [CrossRef]
  31. Daly, S.; Seong, J.; Newcombe, R.; Davies, M.; Nicholson, J.; Edwards, M.; West, N. A randomised clinical trial to determine the effect of a toothpaste containing enzymes and proteins on gum health over 3 months. J. Dent. 2019, 80 (Suppl. S1), S26–S32. [Google Scholar] [CrossRef]
  32. Cunha, E.J.; Auersvald, C.M.; Deliberador, T.M.; Gonzaga, C.C.; Esteban Florez, F.L.; Correr, G.M.; Storrer, C.L.M. Effects of active oxygen toothpaste in supragingival biofilm reduction: A randomized controlled clinical trial. Int. J. Dent. 2019, 2019, 3938214. [Google Scholar] [CrossRef]
  33. Cawley, A.; Golding, S.; Goulsbra, A.; Hoptroff, M.; Kumaran, S.; Marriott, R. Microbiology insights into boosting salivary defences through the use of enzymes and proteins. J. Dent. 2019, 80 (Suppl. S1), S19–S25. [Google Scholar] [CrossRef]
  34. Marconcini, S.; Giammarinaro, E.; Cosola, S.; Oldoini, G.; Genovesi, A.; Covani, U. Effects of non-surgical periodontal treatment on reactive oxygen metabolites and glycemic control in diabetic patients with chronic periodontitis. Antioxidants 2021, 10, 1056. [Google Scholar] [CrossRef]
  35. Gudipaneni, R.K.; Kumar, R.V.; Jesudass, G.; Peddengatagari, S.; Duddu, Y. Short term comparative evaluation of antimicrobial efficacy of tooth paste containing lactoferrin, lysozyme, lactoperoxidase in children with severe early childhood caries: A clinical study. J. Clin. Diagn. Res. 2014, 8, Zc18-20. [Google Scholar] [CrossRef] [PubMed]
  36. Arslan, S.Y.; Leung, K.P.; Wu, C.D. The effect of lactoferrin on oral bacterial attachment. Oral Microbiol. Immunol. 2009, 24, 411–416. [Google Scholar] [CrossRef] [PubMed]
  37. Nagano-Takebe, F.; Miyakawa, H.; Nakazawa, F.; Endo, K. Inhibition of initial bacterial adhesion on titanium surfaces by lactoferrin coating. Biointerphases 2014, 9, 029006. [Google Scholar] [CrossRef]
  38. Modesto, A.; Lima, K.C.; de Uzeda, M. Effects of three different infant dentifrices on biofilms and oral microorganisms. J. Clin. Pediatr. Dent. 2000, 24, 237–243. [Google Scholar] [PubMed]
  39. Pizzo, G.; Guiglia, R.; La Cara, M.; Giuliana, G.; D’Angelo, M. The effects of an amine fluoride/stannous fluoride and an antimicrobial host protein mouthrinse on supragingival plaque regrowth. J. Periodontol. 2004, 75, 852–857. [Google Scholar] [CrossRef] [PubMed]
  40. Gil-Montoya, J.A.; Guardia-López, I.; González-Moles, M.A. Evaluation of the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lysozyme and lactoferrin in elderly patients with dry mouth—A pilot study. Gerodontology 2008, 25, 3–9. [Google Scholar] [CrossRef] [PubMed]
  41. Kirstilä, V.; Lenander-Lumikari, M.; Söderling, E.; Tenovuo, J. Effects of oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia. Acta Odontol. Scand. 1996, 54, 391–397. [Google Scholar] [CrossRef] [PubMed]
  42. Dirix, P.; Nuyts, S.; Poorten, V.V.; Delaere, P.; Bogaert, W.V.d. Efficacy of the BioXtra dry mouth care system in the treatment of radiotherapy-induced xerostomia. Support. Care Cancer 2007, 15, 1429–1436. [Google Scholar] [CrossRef]
  43. Silva, M.P.; Chibebe Junior, J.; Jorjão, A.L.; Machado, A.K.; Oliveira, L.D.; Junqueira, J.C.; Jorge, A.O. Influence of artificial saliva in biofilm formation of Candida albicans in vitro. Braz. Oral Res. 2012, 26, 24–28. [Google Scholar] [CrossRef] [Green Version]
  44. Jager, D.H.; Vissink, A.; Timmer, C.J.; Bronkhorst, E.; Vieira, A.M.; Huysmans, M.C. Reduction of erosion by protein-containing toothpastes. Caries Res. 2013, 47, 135–140. [Google Scholar] [CrossRef]
  45. Fejerskov, O.; Nyvad, B.; Kidd, E. Dental Caries: The Disease and Its Clinical Management, 3rd ed.; Wiley Blackwell: Oxford, UK, 2015. [Google Scholar]
  46. Limeback, H. Comprehensive Preventive Dentistry; John Wiley & Sons: Hoboken, NJ, USA, 2012. [Google Scholar]
  47. Nayak, P.A.; Nayak, U.A.; Khandelwal, V. The effect of xylitol on dental caries and oral flora. Clin. Cosmet. Investig. Dent. 2014, 10, 89–94. [Google Scholar] [CrossRef] [PubMed]
  48. ALHumaid, J.; Bamashmous, M. Meta-analysis on the Effectiveness of Xylitol in Caries Prevention. J. Int. Soc. Prev. Community Dent. 2022, 12, 133–138. [Google Scholar] [CrossRef] [PubMed]
  49. Stefanidou, M.; Maravelias, C.; Dona, A.; Spiliopoulou, C. Zinc: A multipurpose trace element. Arch. Toxicol. 2006, 80, 1–9. [Google Scholar] [CrossRef] [PubMed]
  50. Takino, Y.; Okura, F.; Kitazawa, M.; Iwasaki, K.; Tagami, H. Zinc l-pyrrolidone carboxylate inhibits the UVA-induced production of matrix metalloproteinase-1 by in vitro cultured skin fibroblasts, whereas it enhances their collagen synthesis. Int. J. Cosmet. Sci. 2012, 34, 23–28. [Google Scholar] [CrossRef]
  51. Rajendiran, M.; Trivedi, H.M.; Chen, D.; Gajendrareddy, P.; Chen, L. Recent development of active ingredients in mouthwashes and toothpastes for periodontal diseases. Molecules 2021, 26, 2001. [Google Scholar] [CrossRef]
  52. Fatima, T.; Haji Abdul Rahim, Z.B.; Lin, C.W.; Qamar, Z. Zinc: A precious trace element for oral health care? J. Pak. Med. Assoc. 2016, 66, 1019–1023. [Google Scholar]
  53. Brading, M.G.; Marsh, P.D. The oral environment: The challenge for antimicrobials in oral care products. Int. Dent. J. 2003, 53, 353–362. [Google Scholar] [CrossRef]
  54. Enax, J.; Epple, M. Synthetic hydroxyapatite as a biomimetic oral care agent. Oral Health Prev. Dent. 2018, 16, 7–19. [Google Scholar]
  55. Lelli, M.; Marchetti, M.; Foltran, I.; Roveri, N.; Putignano, A.; Procaccini, M.; Orsini, G.; Mangani, F. Remineralization and repair of enamel surface by biomimetic Zn-carbonate hydroxyapatite containing toothpaste: A comparative in vivo study. Front. Physiol. 2014, 5, 333. [Google Scholar] [CrossRef] [Green Version]
  56. Lynch, R.J. Zinc in the mouth, its interactions with dental enamel and possible effects on caries; a review of the literature. Int. Dent. J. 2011, 61 (Suppl. S3), 46–54. [Google Scholar] [CrossRef]
  57. Marsh, P.D. Controlling the oral biofilm with antimicrobials. J. Dent. 2010, 38 (Suppl. S1), S11–S15. [Google Scholar] [CrossRef] [PubMed]
  58. Becker, L.C.; Bergfeld, W.F.; Belsito, D.V.; Klaassen, C.D.; Marks, J.G., Jr.; Shank, R.C.; Slaga, T.J.; Snyder, P.W.; Alan Andersen, F. Final report of the safety assessment of allantoin and its related complexes. Int. J. Toxicol. 2010, 29, 84s–97s. [Google Scholar] [CrossRef] [PubMed]
  59. Suzuki, N.; Abe-yutori, M.; Chikazawa, T.; Shibasaki, K. Effects of allantoin on periodontal tissue cells. In Proceedings of the 2016 IADR/APR General Session (Seoul, Korea), Seoul, Republic of Korea, 21–25 June 2016. [Google Scholar]
  60. Magaz, V.R.; Llovera, B.F.; Martí, M.; Garre, A. Clinical Impact and Cosmetic Acceptability of Chlorhexidine-enriched Toothpaste and Mouthwash Application on Periodontal Disease: A Randomized Clinical Study. J. Contemp. Dent. Pract. 2018, 19, 1295–1300. [Google Scholar] [CrossRef] [PubMed]
  61. Madrazo-Jiménez, M.; Rodríguez-Caballero, Á.; Serrera-Figallo, M.; Garrido-Serrano, R.; Gutiérrez-Corrales, A.; Gutiérrez-Pérez, J.L.; Torres-Lagares, D. The effects of a topical gel containing chitosan, 0,2% chlorhexidine, allantoin and despanthenol on the wound healing process subsequent to impacted lower third molar extraction. Med. Oral Patol. Oral Cir. Bucal. 2016, 21, e696–e702. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Sáez-Alcaide, L.M.; Molinero-Mourelle, P.; González-Serrano, J.; Rubio-Alonso, L.; Bornstein, M.M.; López-Quiles, J. Efficacy of a topical gel containing chitosan, chlorhexidine, allantoin and dexpanthenol for pain and inflammation control after third molar surgery: A randomized and placebo-controlled clinical trial. Med. Oral Patol. Oral Cir. Bucal. 2020, 25, e644–e651. [Google Scholar] [CrossRef] [PubMed]
  63. Lopez-Lopez, J.; Jan-Pallí, E.; lez-Navarro, B.G.; Jané-Salas, E.; Estrugo-Devesa, A.; Milani, M. Efficacy of chlorhexidine, dexpanthenol, allantoin and chitosan gel in comparison with bicarbonate oral rinse in controlling post-interventional inflammation, pain and cicatrization in subjects undergoing dental surgery. Curr. Med. Res. Opin. 2015, 31, 2179–2183. [Google Scholar] [CrossRef] [PubMed]
  64. Kőhidai, Z.; Takács, A.; Lajkó, E.; Géczi, Z.; Pállinger, É.; Láng, O.; Kőhidai, L. The effects of mouthwashes in human gingiva epithelial progenitor (HGEPp) cells. Clin. Oral Investig. 2022, 26, 4559–4574. [Google Scholar] [CrossRef]
  65. Kamatou, G.P.P.; Viljoen, A.M. A review of the application and pharmacological properties of a-bisabolol and a-bisabolol-rich oils. J. Am. Oil Chem. Soc. 2010, 87, 1–7. [Google Scholar] [CrossRef]
  66. Amora-Silva, B.F.; Ribeiro, S.C.; Vieira, C.L.; Mendes, F.R.; Vieira-Neto, A.E.; Abdon, A.P.V.; Costa, F.N.; Campos, A.R. Clinical efficacy of new α-bisabolol mouthwashes in postoperative complications of maxillofacial surgeries: A randomized, controlled, triple-blind clinical trial. Clin. Oral Investig. 2019, 23, 577–584. [Google Scholar] [CrossRef]
  67. Ramazani, E.; Akaberi, M.; Emami, S.A.; Tayarani-Najaran, Z. Pharmacological and biological effects of alpha-bisabolol: An updated review of the molecular mechanisms. Life Sci. 2022, 304, 120728. [Google Scholar] [CrossRef]
  68. Eddin, L.B.; Jha, N.K.; Goyal, S.N.; Agrawal, Y.O.; Subramanya, S.B.; Bastaki, S.M.A.; Ojha, S. Health benefits, pharmacological effects, molecular mechanisms, and therapeutic potential of α-bisabolol. Nutrients 2022, 14, 1370. [Google Scholar] [CrossRef] [PubMed]
  69. Carl, W.; Emrich, L.S. Management of oral mucositis during local radiation and systemic chemotherapy: A study of 98 patients. J. Prosthet. Dent. 1991, 66, 361–369. [Google Scholar] [CrossRef] [PubMed]
  70. Forrer, M.; Kulik, E.M.; Filippi, A.; Waltimo, T. The antimicrobial activity of alpha-bisabolol and tea tree oil against Solobacterium moorei, a Gram-positive bacterium associated with halitosis. Arch. Oral Biol. 2013, 58, 10–16. [Google Scholar] [CrossRef] [PubMed]
  71. Wang, S.T.; Neo, B.H.; Betts, R.J. Glycosaminoglycans: Sweet as sugar targets for topical skin anti-aging. Clin. Cosmet. Investig. Dermatol. 2021, 14, 1227–1246. [Google Scholar] [CrossRef]
  72. Pogrel, M.A.; Low, M.A.; Stern, R. Hyaluronan (hyaluronic acid) and its regulation in human saliva by hyaluronidase and its inhibitors. J. Oral Sci. 2003, 45, 85–91. [Google Scholar] [CrossRef] [Green Version]
  73. Gupta, R.C.; Lall, R.; Srivastava, A.; Sinha, A. Hyaluronic acid: Molecular mechanisms and therapeutic trajectory. Front. Vet. Sci. 2019, 6, 192. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Rodrigues, S.V.; Acharya, A.B.; Bhadbhade, S.; Thakur, S.L. Hyaluronan-containing mouthwash as an adjunctive plaque-control agent. Oral Health Prev. Dent. 2010, 8, 389–394. [Google Scholar] [PubMed]
  75. Gizligoz, B.; Ince Kuka, G.; Tunar, O.L.; Ozkan Karaca, E.; Gursoy, H.; Kuru, B. Plaque inhibitory effect of hyaluronan-containing mouthwash in a 4-day non-brushing model. Oral Health Prev. Dent. 2020, 18, 61–70. [Google Scholar] [PubMed]
  76. Trombelli, L.; Simonelli, A.; Pramstraller, M.; Guarnelli, M.E.; Fabbri, C.; Maietti, E.; Farina, R. Clinical efficacy of a chlorhexidine-based mouthrinse containing hyaluronic acid and an antidiscoloration system in patients undergoing flap surgery: A triple-blind, parallel-arm, randomized controlled trial. Int. J. Dent. Hyg. 2018, 16, 541–552. [Google Scholar] [CrossRef] [PubMed]
  77. Genovesi, A.; Barone, A.; Toti, P.; Covani, U. The efficacy of 0.12% chlorhexidine versus 0.12% chlorhexidine plus hyaluronic acid mouthwash on healing of submerged single implant insertion areas: A short-term randomized controlled clinical trial. Int. J. Dent. Hyg. 2017, 15, 65–72. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  78. Tüzüner, T.; Ulusoy, A.T.; Baygin, O.; Yahyaoglu, G.; Yalcin, I.; Buruk, K.; Nicholson, J. Direct and transdentinal (indirect) antibacterial activity of commercially available dental gel formulations against Streptococcus mutans. Med. Princ. Pract. 2013, 22, 397–401. [Google Scholar] [CrossRef] [Green Version]
  79. Talib, H.J.; Mousa, H.A.; Mahmood, A.A. Assessment of the plaque-induced gingivitis patient with and without hyaluronic acid and xylitol toothpaste. J. Int. Soc. Prev. Community Dent. 2021, 11, 138–143. [Google Scholar] [PubMed]
  80. Aydinyurt, H.S.; Akbal, D.; Altindal, D.; Bozoglan, A.; Ertugrul, A.S.; Demir, H. Evaluation of biochemical and clinical effects of hyaluronic acid on non-surgical periodontal treatment: A randomized controlled trial. Ir. J. Med. Sci. 2020, 189, 1485–1494. [Google Scholar] [CrossRef] [PubMed]
  81. Boccalari, E.; Tadakamadla, S.K.; Occhipinti, C.; Lanteri, V.; Maspero, C. Evaluation of the effectiveness of a novel mouth rinse containing hyaluronic acid and hydrogen peroxide on gingivitis: A randomized pilot controlled trial. Clin. Exp. Dent. Res. 2022, 8, 673–679. [Google Scholar] [CrossRef] [PubMed]
  82. Abdulkareem, A.A.; Al Marah, Z.A.; Abdulbaqi, H.R.; Alshaeli, A.J.; Milward, M.R. A randomized double-blind clinical trial to evaluate the efficacy of chlorhexidine, antioxidant, and hyaluronic acid mouthwashes in the management of biofilm-induced gingivitis. Int. J. Dent. Hyg. 2020, 18, 268–277. [Google Scholar] [CrossRef] [PubMed]
  83. Tadakamadla, S.K.; Bharathwaj, V.V.; Duraiswamy, P.; Sforza, C.; Tartaglia, G.M. Clinical efficacy of a new cetylpyridinium chloride-hyaluronic acid-based mouthrinse compared to chlorhexidine and placebo mouthrinses-A 21-day randomized clinical trial. Int. J. Dent. Hyg. 2020, 18, 116–123. [Google Scholar] [CrossRef]
  84. Muñoz-Cámara, D.; Pardo-Zamora, G.; Camacho-Alonso, F. Postoperative effects of intra-alveolar application of 0.2% chlorhexidine or 1% hyaluronic acid bioadhesive gels after mandibular third molar extraction: A double-blind randomized controlled clinical trial. Clin. Oral Investig. 2021, 25, 617–625. [Google Scholar] [CrossRef]
  85. Yang, H.; Kim, J.; Kim, J.; Kim, D.; Kim, H.J. Non-inferiority study of the efficacy of two hyaluronic acid products in post-extraction sockets of impacted third molars. Maxillofac. Plast. Reconstr. Surg. 2020, 42, 40. [Google Scholar] [CrossRef]
  86. Rodríguez Zorrilla, S.; Blanco Carrión, A.; García García, A.; Galindo Moreno, P.; Marichalar Mendía, X.; Seoane Prado, R.; Pérez Estévez, A.J.; Pérez-Sayáns, M. Effect of antiseptic gels in the microbiologic colonization of the suture threads after oral surgery. Sci. Rep. 2020, 10, 8360. [Google Scholar] [CrossRef]
  87. Agha-Hosseini, F.; Pourpasha, M.; Amanlou, M.; Moosavi, M.S. Mouthwash containing vitamin E, triamcinolon, and hyaluronic acid compared to triamcinolone mouthwash alone in patients with radiotherapy-induced oral mucositis: Randomized clinical trial. Front. Oncol. 2021, 11, 614877. [Google Scholar] [CrossRef]
  88. Bardellini, E.; Amadori, F.; Schumacher, R.F.; D’Ippolito, C.; Porta, F.; Majorana, A. Efficacy of a solution composed by verbascoside, polyvinylpyrrolidone (PVP) and sodium hyaluronate in the treatment of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. J. Pediatr. Hematol. Oncol. 2016, 38, 559–562. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  89. Vokurka, S.; Skardova, J.; Hruskova, R.; Kabatova-Maxova, K.; Svoboda, T.; Bystricka, E.; Steinerova, K.; Koza, V. The effect of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) on oral microbial colonization and pain control compared with other rinsing solutions in patients with oral mucositis after allogeneic stem cells transplantation. Med. Sci. Monit. 2011, 17, Cr572–Cr576. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  90. Ruggiero, T.; Pol, R.; Camisassa, D.; Arata, V.; Martino, I.; Giaccone, L.; Carossa, S. Use of sodium hyaluronate and synthetic amino acid precursors of collagen for the symptomatic treatment of mucositis in patients undergoing haematopoietic stem cell transplants. J. Biol. Regul. Homeost. Agents 2016, 30, 889–894. [Google Scholar] [PubMed]
  91. Polizzi, A.; Santonocito, S.; Lo Giudice, A.; Alibrandi, A.; De Pasquale, R.; Isola, G. Analysis of the response to two pharmacological protocols in patients with oral lichen planus: A randomized clinical trial. Oral Dis. 2021. online ahead of print. [Google Scholar] [CrossRef] [PubMed]
  92. Santonocito, S.; Polizzi, A.; De Pasquale, R.; Ronsivalle, V.; Lo Giudice, A.; Isola, G. Analysis of the efficacy of two treatment protocols for patients with symptomatic oral lichen planus: A randomized clinical trial. Int. J. Environ. Res. Public Health 2020, 18, 56. [Google Scholar] [CrossRef] [PubMed]
  93. Nolan, A.; Badminton, J.; Maguire, J.; Seymour, R.A. The efficacy of topical hyaluronic acid in the management of oral lichen planus. J. Oral Pathol. Med. 2009, 38, 299–303. [Google Scholar] [CrossRef]
  94. Dalessandri, D.; Zotti, F.; Laffranchi, L.; Migliorati, M.; Isola, G.; Bonetti, S.; Visconti, L. Treatment of recurrent aphthous stomatitis (RAS; aphthae; canker sores) with a barrier forming mouth rinse or topical gel formulation containing hyaluronic acid: A retrospective clinical study. BMC Oral Health 2019, 19, 153. [Google Scholar] [CrossRef]
  95. De Araújo Nobre, M.; Cintra, N.; Maló, P. Peri-implant maintenance of immediate function implants: A pilot study comparing hyaluronic acid and chlorhexidine. Int. J. Dent. Hyg. 2007, 5, 87–94. [Google Scholar] [CrossRef]
  96. Park, M.S.; Chang, J.Y.; Kang, J.H.; Park, K.P.; Kho, H.S. Rheological properties of hyaluronic acid and its effects on salivary enzymes and candida. Oral Dis. 2010, 16, 382–387. [Google Scholar] [CrossRef]
  97. López-Jornet, P.; Camacho-Alonso, F.; Martinez-Canovas, A. Clinical evaluation of polyvinylpyrrolidone sodium hyaluronate gel and 0.2% chlorhexidine gel for pain after oral mucosa biopsy: A preliminary study. J. Oral Maxillofac. Surg. 2010, 68, 2159–2163. [Google Scholar] [CrossRef] [PubMed]
  98. Palaia, G.; Tenore, G.; Tribolati, L.; Russo, C.; Gaimari, G.; Del Vecchio, A.; Romeo, U. Evaluation of wound healing and postoperative pain after oral mucosa laser biopsy with the aid of compound with chlorhexidine and sodium hyaluronate: A randomized double blind clinical trial. Clin. Oral Investig. 2019, 23, 3141–3151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  99. Bural, C.; Güven, M.; Kayacıoğlu, B.; Ak, G.; Bayraktar, G.; Bilhan, H. Effect of over-the-counter topical agents on denture-induced traumatic lesions: A clinical study. Int. J. Prosthodont. 2018, 31, 481–484. [Google Scholar] [CrossRef] [PubMed]
  100. Dong, Q.; Zhong, X.; Zhang, Y.; Bao, B.; Liu, L.; Bao, H.; Bao, C.; Cheng, X.; Zhu, L.; Lin, Q. Hyaluronic acid-based antibacterial hydrogels constructed by a hybrid crosslinking strategy for pacemaker pocket infection prevention. Carbohydr. Polym. 2020, 245, 116525. [Google Scholar] [CrossRef] [PubMed]
  101. Mazur, M.; Ndokaj, A.; Bietolini, S.; Nisii, V.; Duś-Ilnicka, I.; Ottolenghi, L. Green dentistry: Organic toothpaste formulations. A literature review. Dent. Med. Probl. 2022, 59, 461–474. [Google Scholar] [CrossRef]
  102. Cieplik, F.; Kara, E.; Muehler, D.; Enax, J.; Hiller, K.-A.; Maisch, T.; Buchalla, W. Antimicrobial efficacy of alternative compounds for use in oral care towards biofilms from caries-associated bacteria in vitro. MicrobiologyOpen 2018, 8, e00695. [Google Scholar] [CrossRef] [Green Version]
  103. Amaechi, B.T.; Farah, R.; Liu, J.A.; Phillips, T.S.; Perozo, B.I.; Kataoka, Y.; Meyer, F.; Enax, J. Remineralization of molar incisor hypomineralization (MIH) with a hydroxyapatite toothpaste: An in-situ study. BDJ Open 2022, 8, 33. [Google Scholar] [CrossRef]
  104. Amaechi, B.T.; AbdulAzees, P.A.; Alshareif, D.O.; Shehata, M.A.; Lima, P.P.d.C.S.; Abdollahi, A.; Kalkhorani, P.S.; Evans, V. Comparative efficacy of a hydroxyapatite and a fluoride toothpaste for prevention and remineralization of dental caries in children. BDJ Open 2019, 5, 18. [Google Scholar] [CrossRef] [Green Version]
  105. Amaechi, B.T.; AbdulAzees, P.A.; Okoye, L.O.; Meyer, F.; Enax, J. Comparison of hydroxyapatite and fluoride oral care gels for remineralization of initial caries: A pH-cycling study. BDJ Open 2020, 6, 9. [Google Scholar] [CrossRef]
  106. Amaechi, B.T.; Phillips, T.S.; Evans, V.; Ugwokaegbe, C.P.; Luong, M.N.; Okoye, L.O.; Meyer, F.; Enax, J. The potential of hydroxyapatite toothpaste to prevent root caries: A pH-cycling study. Clin. Cosmet. Investig. Dent. 2021, 13, 315–324. [Google Scholar] [CrossRef]
  107. Tschoppe, P.; Zandim, D.L.; Martus, P.; Kielbassa, A.M. Enamel and dentine remineralization by nano-hydroxyapatite toothpastes. J. Dent. 2011, 39, 430–437. [Google Scholar] [CrossRef] [Green Version]
  108. Cieplik, F.; Rupp, C.M.; Hirsch, S.; Muehler, D.; Enax, J.; Meyer, F.; Hiller, K.-A.; Buchalla, W. Ca2+ release and buffering effects of synthetic hydroxyapatite following bacterial acid challenge. BMC Oral Health 2020, 20, 85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  109. Jones, C.G. Chlorhexidine: Is it still the gold standard? Periodontology 2000 1997, 15, 55–62. [Google Scholar] [CrossRef] [PubMed]
  110. Frese, C.; Wohlrab, T.; Sheng, L.; Kieser, M.; Krisam, J.; Wolff, D. Clinical effect of stannous fluoride and amine fluoride containing oral hygiene products: A 4-year randomized controlled pilot study. Sci. Rep. 2019, 9, 7681. [Google Scholar] [CrossRef] [PubMed]
  111. Ekambaram, M.; Itthagarun, A.; King, N.M. Ingestion of fluoride from dentifrices by young children and fluorosis of the teeth—A literature review. J. Clin. Pediatr. Dent. 2011, 36, 111–121. [Google Scholar] [CrossRef] [PubMed]
  112. Cieplik, F.; Jakubovics, N.S.; Buchalla, W.; Maisch, T.; Hellwig, E.; Al-Ahmad, A. Resistance toward chlorhexidine in oral bacteria—Is there cause for concern? Front Microbiol. 2019, 10, 587. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  113. Tabatabaei, M.H.; Mahounak, F.S.; Asgari, N.; Moradi, Z. Cytotoxicity of the ingredients of commonly used toothpastes and nouthwashes on human gingival fibroblasts. Front. Dent. 2019, 16, 450–457. [Google Scholar] [CrossRef] [PubMed]
  114. Nocerino, N.; Fulgione, A.; Iannaccone, M.; Tomasetta, L.; Ianniello, F.; Martora, F.; Lelli, M.; Roveri, N.; Capuano, F.; Capparelli, R. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals. Int. J. Nanomed. 2014, 9, 1175–1184. [Google Scholar]
  115. Paszynska, E.; Pawinska, M.; Gawriolek, M.; Kaminska, I.; Otulakowska-Skrzynska, J.; Marczuk-Kolada, G.; Rzatowski, S.; Sokolowska, K.; Olszewska, A.; Schlagenhauf, U.; et al. Impact of a toothpaste with microcrystalline hydroxyapatite on the occurrence of early childhood caries: A 1-year randomized clinical trial. Sci. Rep. 2021, 11, 2650. [Google Scholar] [CrossRef]
  116. Hannig, C.; Basche, S.; Burghardt, T.; Al-Ahmad, A.; Hannig, M. Influence of a mouthwash containing hydroxyapatite microclusters on bacterial adherence in situ. Clin. Oral Investig. 2013, 17, 805–814. [Google Scholar] [CrossRef]
  117. Brauner, E.; Di Cosola, M.; Ambrosino, M.; Cazzolla, A.P.; Dioguardi, M.; Nocini, R.; Topi, S.; Mancini, A.; Maggiore, M.E.; Scacco, S.; et al. Efficacy of bio-activated anti-calculus toothpaste on oral health: A single-blind, parallel-group clinical study. Minerva Dent. Oral Sci. 2021, 71, 31–38. [Google Scholar]
  118. Fabritius-Vilpoux, K.; Enax, J.; Mayweg, D.; Meyer, F.; Herbig, M.; Raabe, D.; Fabritius, H.-O. Ultrastructural changes of bovine tooth surfaces under erosion in presence of biomimetic hydroxyapatite. Bioinspired Biomim. Nanobiomater. 2021, 10, 132–145. [Google Scholar] [CrossRef]
Biomimetics 07 00250 g001 550
Figure 1. Structural formulas of the analyzed ingredients in this review used in combination with hydroxyapatite in oral care products (structural formulas according to ref. [20]; due to its complexity, the structure of lactoferrin is not shown; details have been published e.g., by Baker et al. [21]).
Figure 1. Structural formulas of the analyzed ingredients in this review used in combination with hydroxyapatite in oral care products (structural formulas according to ref. [20]; due to its complexity, the structure of lactoferrin is not shown; details have been published e.g., by Baker et al. [21]).
Biomimetics 07 00250 g001
Table
Table 1. Total results of the PubMed search of selected ingredients that are used as adjunct ingredients in hydroxyapatite oral care products (for details on the search see Section 2).
Table 1. Total results of the PubMed search of selected ingredients that are used as adjunct ingredients in hydroxyapatite oral care products (for details on the search see Section 2).
IngredientTotal Number of
Results		Number of Included StudiesExcluded Studies
lactoferrin3416Not in the scope of this review: 13
Review articles: 3
Articles in other languages than English: 1
Case reports: 1
Animal studies: 0
xylitol244Due to the high number of studies, evaluation will be referred to other reviews
zinc2026Due to the high number of studies, evaluation will be referred to other reviews
allantoin135Not in the scope of this review: 3
Review articles: 0
Articles in other languages than English: 4
Case reports: 0
Animal studies: 1
bisabolol103Not in the scope of this review: 6
Review articles: 0
Articles in other languages than English: 1
Case reports: 0
Animal studies: 0
hyaluronic acid/hyaluronate5227Not in the scope of this review: 15
Review articles: 6
Articles in other languages than English: 3
Case reports: 0
Animal studies: 1
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Enax, J.; Amaechi, B.T.; Schulze zur Wiesche, E.; Meyer, F. Overview on Adjunct Ingredients Used in Hydroxyapatite-Based Oral Care Products. Biomimetics 2022, 7, 250. https://doi.org/10.3390/biomimetics7040250

AMA Style

Enax J, Amaechi BT, Schulze zur Wiesche E, Meyer F. Overview on Adjunct Ingredients Used in Hydroxyapatite-Based Oral Care Products. Biomimetics. 2022; 7(4):250. https://doi.org/10.3390/biomimetics7040250

Chicago/Turabian Style

Enax, Joachim, Bennett T. Amaechi, Erik Schulze zur Wiesche, and Frederic Meyer. 2022. "Overview on Adjunct Ingredients Used in Hydroxyapatite-Based Oral Care Products" Biomimetics 7, no. 4: 250. https://doi.org/10.3390/biomimetics7040250

Article Metrics

Back to TopTop