Antimicrobial and Mechanical Effects of Zeolite Use in Dental Materials: A Systematic Review

Abstract

Objective

Ion-incorporated zeolite is a widely used antimicrobial material studied for various dental applications. At present, there is no other systematic review that evaluates the effectiveness of zeolite in all dental materials. The purpose of this study was to review all available literature that analyzed the antimicrobial effects and/or mechanical properties of zeolite as a restorative material in dentistry.

Material and Methods

Following PRISMA guidelines, an exhaustive search of PubMed, Ovid Medline, Scopus, Embase, and the Dentistry & Oral Sciences Source was conducted. No language or time restrictions were used and the study was conducted from June 1, 2020 to August 17, 2020. Only full text articles were selected that pertained to the usage of zeolite in dental materials including composite resin, bonding agents, cements, restorative root material, cavity base material, prosthesis, implants, and endodontics.

Results

At the beginning of the study, 1534 studies were identified, of which 687 duplicate records were excluded. After screening for the title, abstract, and full texts, 35 articles remained and were included in the qualitative synthesis. An Inter-Rater Reliability (IRR) test, which included a percent user agreement and reliability percent, was conducted for each of the 35 articles chosen.

Conclusion

Although ion-incorporated zeolite may enhance the antimicrobial properties of dental materials, the mechanical properties of some materials, such as MTA and acrylic resin, may be compromised. Therefore, since the decrease in mechanical properties depends on zeolite concentration in the restorative material, it is generally recommended to add 0.2-2% zeolite by weight.

Introduction

Zeolite, an aluminosilicate with a tetrahedral crystalline structure, has extensive applications ranging from ecology to dentistry (1, 2). Zeolite is particularly useful to these fields due to its unique porous structure, which creates negatively charged channels and cavities that can hold cations, hydroxyl groups, and water molecules (1). Recently, the property of zeolite to uptake and release ions, combined with its superior biocompatibility and long-lasting effects, has attracted the attention of researchers, thus increasing their interest in the use of compounds in dental research (2).

In addition to solely adding zeolite to materials, many studies in dentistry have attempted to combine zeolite with inorganic antimicrobial ions, such as silver and zinc, for controlled release (2). Particularly, most of the studies focus on silver-incorporated zeolite (AgZ) since zeolite has a strong affinity for silver ions. In addition, silver ions are less toxic to human tissues than other metallic ions, such as copper and mercury (3, 4). When cations become available in the surrounding oral environment, zeolite exchanges the environmental cation with its embedded silver ions. This, in turn, it only occurs with the presence of moisture and until the silver concentration meets the local equilibrium value. Therefore, AgZ may offer targeted and controlled release of antimicrobial ions in the oral microbiome (5).

Furthermore, ion-embedded zeolite may serve as a potential antimicrobial agent towards pathogenic oral microorganisms. When ions released from zeolite encounter specific oral microbes, their development may be hindered by causing the inactivation of key enzymes, interruption of RNA replication, and blockage of microbial respiration (5). Therefore, incorporation of cations into zeolite may potentially decrease oral bacterial growth when added to dental materials.

When zeolite is incorporated into dental materials for antimicrobial effect, it is also important to consider the effect on the mechanical properties of the material. Common activities such as mastication and speech exert forces on teeth and materials incorporated into dentition. Thus, it is critical to the efficacy of dental operations if the materials used can withstand these forces without compromising their strength. Properties imperative to the success of long-term dental operations includes flexural strength, bond strength to tooth structure, compressive strength, setting time, and surface microhardness (6). If zeolite can be incorporated into dental materials without hindering their mechanical properties, there can be a potential reduction in oral infections while reducing failures of dental restorations.

In this systematic review, the antimicrobial and mechanical properties of zeolite in different branches of dentistry such as endodontics, prosthetics, implantology, and restorative dentistry are analyzed. Specifically, the available literature was reviewed to determine if adding silver (or zinc) zeolite to dental materials would increase the antimicrobial effectiveness without inhibiting the strength and hardness of materials. The aim of this systematic study was to review both in vitro and in vivo studies that evaluated the antimicrobial effects and mechanical properties of zeolite as a material in dentistry.

Material and Methods

Literature search strategy

An exhaustive search of PubMed, Ovid Medline, Scopus, Embase, and the Dentistry & Oral Sciences Source was conducted between June 1, 2020 and August 17, 2020. All published studies within the databases were screened for eligibility. There were no limitations set on the year or language of the publication. A controlled vocabulary was used (MeSH terms in Pubmed, Subject Headings in Ovid Medline, Emtree terms in Embase) across all databases as well as a search for free terms in the titles and abstracts. The grey literature search was conducted through ProQuest Dissertations & Theses Global and Trip Database. The searches through the electronic databases were separately completed by two authors (J.H. and S.L.). The following search terms were used: MeSH terms: “zeolites”, “biomedical and dental materials”, “dental cavity lining”, “resin cements”, “dental cements”, “dental restoration, permanent”, “dental restoration, temporary”, “composite resins”, “ceramics”, “dental porcelain”, “dental veneers”, “dentures”, “acrylic resin”; Subject Headings: “dental cements”, “dental cavity lining”, “resin cements”, “dental restoration, permanent”; “composite resin”, “ceramics”, “dental porcelain”, “dental veneers”, “dentures”, “acrylic resin”; Emtree Terms: “dental materials”, “resin cement”, “dental restoration”, “dentures”, “dental porcelain”, “dental veneers”, “composite resin”, “dental prosthesis and implant”, “biomedical and dental materials.” Free Terms: zeolite, clinoptilolite, dental materials, dental cements, dental restoration, dental base material, dental liners, dental ceramics, dental porcelain, dental veneers, dentures, dental acrylic resin.

Eligibility Criteria

Studies that pertained to the usage of zeolite in dental materials such as composite resin, bonding agents, cements, restorative root material, cavity base material, prosthesis, implants, and endodontics were included in this systematic review. In addition, only full texts were selected for inclusion. Zeolite used in oral rinses or oral medicaments was excluded as well as those studies pertaining to tissue conditioners. Literature reviews and abstracts were excluded to meet the full-text-only eligibility criteria.

Screening and Selection

The studies that were collected were screened independently by two researchers (J.H. and S.L.) for titles and abstracts that met the identified inclusion criteria. Differences in opinions were discussed between the two researchers until a consensus was reached. Following the discussion, the two reviewers separately screened the selected full texts for eligibility. Disagreements were discussed until a consensus was reached. Due to the COVID-19 pandemic, the numbers of active libraries were smaller than normal. Therefore, with all resources exhausted, the full texts of 3 chosen articles were still unable to be procured and included in the analysis portion of the systematic review. At last, the references of the selected articles were reviewed, and eligibility was determined based on the inclusion criteria. Disagreements were resolved between the two reviewers and discussions with a mentor (F.O.).

Data Extraction

Prior to data extraction, a protocol was agreed upon by two of the authors (J.H. and S.L.). Data were then extracted from the selected full text articles and organized on an excel sheet. The two authors extracted the data including authors, publication year, type of study, antimicrobial/mechanical properties, sample size, materials used, results, microbes tested, and risk of bias, Table 1, Table 2.

Table 1. Summary of the studies included in the systematic review.

Author, Year	Type of Study	Property	n	Materials Used	Results	Microbes Tested
Saengmee-Anupharb et al [10] (2013)	In vitro	A	3 per group	AgZ, AgZrPSi, AgZrP	All inorganic materials with silver had antimicrobial effects.	S. mutans, L. casei, C. albicans, S. aureus
Cinar et al [14] (2008)	In vitro	A	5 per material	GIC (Endion), AgZ	AgZ increased the antimicrobial effects	S. milleri, S. aureus, E. faecalis
Can-Karabulut et al [21] (2010)	In vitro	M	10 per material	GIC, zeolite, bone hydroxyapatite, provisional cement	Bond strength decreased with zeolite in cement.	N/A
Chung et al [20] (2001)	RCT	M	10 per subgroup	Ketac-Endo, KT-308, ZUT	ZUT and KT-308 showed highest bond strength.	N/A
Ghatole et al [28] (2016)	In vitro	A	3 per group	MTA, AgZ, CHX	MTA with AgZ showed the greatest efficacy against E. faecalis.	E. faecalis
Ghivari et al [25] (2017)	In vitro	A	5 per material	Na Hypochlorite, Octenidine, AgZ	AgZ showed the least antimicrobial effectiveness.	E. faecalis, S. aureus, C. albicans
Hotta et al [3] (1998)	In vitro	B	6 per group	Ag-Zn-Zeolite, SiO2 filler and urethane acrylate paste	Ag-Zn-Ze inhibited S. mutans and S. mitis but not S. salivarius or S. sanguis.	S. mutans, S. mitis, S. salivarius, S. sanguis
Kawahara et al [4] (2000)	In vitro	A	6 per group	Zeomic, AgZ	AgZ inhibited microbial growth under anaerobic conditions.	P. gingivalis actinomycetemcomitans, S. mutans, A. viscosus, S. aureus
Kim et al [16] (2016)	In vitro	B	N/S	CHX-loaded zeolite nanoparticles, GIC	GIC + CHX/Zeolite inhibited S. mutans. No decrease in compressive or bond strength	S. mutans
Kuroki et al [37] (2010)	In vitro	A	6 per material	self-cured acrylic resin (UNIFAST III), zeomic, bactekiller, novaron	Adding zeomic decreased S. mutans	S. mutans
Lee et al [13] (2007)	In vitro	B	N/S	Zeomic, GIC	Zeomic improved antimicrobial properties. Below 3% wt retained compressive strength.	S. mutans
Li et al [23] (2020)	RCT	A	N/S	EMT nano-zeolites, silver ions, dental adhesive (ASB2)	Inhibited biofilm growth/attachment.	S. mutans, S. gordonii, S. sanguinis
Mabrouk et al [15] (2013)	In vitro	A	N/S	ZnZ, AgZ, GIC	Adding ZnZ or AgZ to GIC inhibited bacteria.	B. subtilis, C. albicans, E. coli, S. aureus
Padachey et al [18] (2000)	In vitro	A	10 per group	GIC, gutta percha, ZUT	ZUT was not more effective than GIC. But gutta percha improved the resistance to bacterial ingress.	E. faecalis
Partoazar et al [11] (2019)	In vitro	A	N/S	nano-ZnO zeolite, ZnO zeolite	NanoZnO/zeolite was effective in inhibiting E. faecalis biofilm	E. faecalis
Cinar et al [29] (2013)	In vitro	M	3 per material	MTA powder, AgZ	Adding AgZ to MTA didn't decrease physio-chemical properties.	N/A
El-Guindy et al [24] (2010)	In vitro	M	30 per group, 10 per subgroup	Rely X Unicem, G bond, ZnZ	Pretreatment of dentin with G bond and ZnZ increased bond strength between dentin/alloy.	N/A
Ghasemi et al [30] (2019)	In vitro	M	20 per group	MTA powder, 2% Ag-Zn-Ze composite	MTA with 2% Ag-Zn-Ze decreased push-out bond strength.	N/A
Ghatole et al [26] (2016)	In vitro	A	4 per group	Calcium hydroxide, AgZ, 2% CHX	AgZ in calcium hydroxide increased antimicrobial activity	E. faecalis
Casemiro et al [40] (2008)	In vitro	B	10 per group	Microwave-polymerized acrylic resin, Heat-polymerized resins, AgZ	Acrylic resin with Ag-Zn-Ze increased antimicrobial effects.	C. albicans and S. mutans
Malic et al [38] (2019)	In vitro	A	6 per group	Dental acrylics, AgZ, Na-zeolite	Adding zeolite to dental acrylics increased antimicrobial effect.	S. mutans, F. nucleatum, C. albicans
Odabas et al [27] (2011)	In vitro	A	5 per group	AgZ, MTA	MTA with zeolite increased antimicrobial effects except against P. intermedia and A. israelii.	S. aureus, E. faecalis, E. coli, , C. albicans, P. gingivalis, C. A. israelii, P. intermedia
Patel et al [17] (2000)	In vitro	A	108 per group	KT-308, Zeomic	Regardless of concentration, all ZUT inhibited E. faecalis at 15 hours.	E. Faecalis
Sandomierski et al [22] (2019)	In vitro	M	10 per material	Zeolite filler, diazonium cation methacrylic resin-based composite	Diazonium-modified zeolite fillers improved compressive and flexural strength.	N/A
Saravanan et al [32] (2015)	In vitro	A	30 patients	AgZ, soft liners	Soft liner with AgZ inhibited bacterial growth	c. albicans, gram negative bacteria
Tamanai-Shacoor et al [12] (2014)	In vitro	B	3 per group	AgZ, ASCOP	AgZ with ASCOP inhibited P. gingivalis but not S. gordonii growth.	P. gingivalis, S. gordonii
Naji et al [34] (2017)	In vitro	M	10 per group	Sodalite, alumina, ZTA, glass	Sodalite-infiltrated ceramics had higher shear bond strength than glass-infiltrated.	N/A
Naji et al [35] (2018)	In vitro	M	20 per group	KBr-Sodalite, porous alumina, ZTA	Increasing sintering temp of SOD-ZTA/A increased hardness and bond strength.	N/A
Naji et al [33] (2016)	In vitro	M	10 per group	sodalite, zeolite-infiltrated alumina (IA-SOD), ZTA, glass	Sodalite-infiltrated ZTA had increased fracture toughness.	N/A
Naji et al [36] (2016)	In vitro	M	10 per group	Sodalite, alumina, ZTA, glass	Sodalite infiltrated alumina and ZTA were in the acceptable range of hardness and flexural strength.	N/A
Yadav et al [41] (2015)	In vitro	M	10 per group	Fluconazole, CHX Gluconate, Ag-Zn-Ze, PMMA	Flexural strength decreased significantly	N/A
Nakanoda et al [39] (1995)	In vitro	B	4 per group	Zeomic, acrylic resin	Tensile and bending strength decreased in zeolite containing resin,	C. albicans
Samiei et al [31] (2017)	In vitro	M	15 per group	MTA, 2% Ag-Zn-Ze	Mixing MTA with 2% Ze-Ag-Zn decreased compressive strength.	N/A
Wang et al [42] (2011)	In vitro	A	3 per material	Titanium alloy, AgZ, ZTA, AgZ titanium alloy	Zeolite coating on implant reduced bacterial growth	S. aureus
McDougall et al [19] (1999)	In vitro	A	10 per group	ZUT, Kerr sealer, KT-308, gutta percha	E. faecalis penetration increased in canals filled with ZUT	E. faecalis
Abbreviations: N/S: Not Stated; N/A: Not Applicable; A: Antimicrobial; M: Mechanical; B: Both Antimicrobial and Mechanical; PMMA: Polymethylmethacrylate; ZTA: Zirconium Toughened Alumina; AgZ: Silver-Incorporated Zeolite; ZnZ: Zinc-Incorporated Zeolite; Ag-Zn-Ze: Silver-Zinc-Incorporated Zeolite; MTA: Mineral Trioxide Aggregate; GIC: Glass Ionomer Cement; CHX: chlorhexidine; ZUT: AgZ with KT-308 GIC; Zeomic: a synthetic AgZ; ASCOP: polyphenol-rich extract of A. nodosum

Table 2. IRR Values of Studies in the Systematic Review.

	% User Agreement	Kappa	% data that are reliable (through Cohen’s Kappa Test)	Level of Agreement
Sample Size	80%	0.304	9.24%	Minimal
Control	97%	0.788	62.10%	Moderate
Blinding Operator	100.00%	1	100%	Almost Perfect
Single Operator	94%	0.693	40.80%	Moderate
Standardized Sample Prep	74.30%	0.457	20.90%	Weak

Assessment of Risk of Bias of Reviewed Papers

For in vitro studies and randomized control trials, the risk of bias assessment was considered based on a previous study (7), and each study was assessed on the basis of the following five parameters: I) sample size, II) presence of control, III) blinding of the operator, IV) standardized sample preparation, and V) single operator.

For each parameter I-IV, a score of 0 was given to an article if the criteria were reported clearly, a score of 1 was given to an article if the criteria were vague or insufficiently reported, and a score of 2 was given to an article if the information was not present. For parameter V, a score of 0 was given to an article if there was one operator, a score of 1 was given to an article if there were more operators, and a score of 2 was given to an article if the information was not present.

The five parameter scores for each article were then added for a cumulative score. Articles that were at low risk of bias scored between 0-3, moderate risk of bias scored between 4-7, and high risk of bias scored between 8-10. Two authors (J.H. and S.L.) independently assessed the risk of bias criteria for each article in duplicate, and any disagreements during the evaluation were later discussed and a consensus was reached.

Inter-rate Reliability (IRR)

An inter-rater reliability (IRR) test within the risk of bias test was conducted using a kappa calculator. Percent user agreement was calculated by taking the number of studies given the same risk of bias scores by both authors and dividing it by the total number of studies. The same risks of bias scores were considered in order to use the Cohen’s Kappa test (8), and the resulting kappa values are reported, Table 2. To obtain the percent data that are reliable, the kappa values were squared. From these percentages, a level of agreement was described for each parameter (8).

Results

Search and Selection

The selection process is summarized in the Prisma Flow Chart shown in Figure 1 following Moher et al. (9). A database, grey literature, and reference search yielded 1534 studies, of which 687 duplicate records were excluded. The remaining 847 records were screened for title and abstract, and 801 were removed since they did not meet the eligibility criteria. 46 remaining articles were assessed for eligibility by examining the full-texts, and 11 articles did not meet the eligibility criteria and were therefore excluded. Of the remaining 35 articles included in the qualitative synthesis, 17 studied antimicrobial effects, 12 studied mechanical properties, and 6 studied both properties, Table 1.

Figure 1.

The Prisma Flow Diagram. *: 2 studied remineralizing potential, 1 studied biocompatibility, 2 studied color stability, 1 studied porosity, 1 studied surface roughness, 3 were unable to be accessed due to COVID-19 library closures, 1 unable to be accessed in English. For more information on the PRISMA Flow Chart, visit www.prisma-statement.org.

Risk of Bias Test of the Studies in the Systematic Review

Supplementary Table 3 [S3 Table] shows the risk of bias data of the 35 articles analyzed following the methods outlined by Astudillo-Rubio et al. (7). As shown in the table, the majority of papers were given a score of 2 by both authors in the “blinding operator” and “single operator” parameters for failing to provide any pertinent information. All studies had a moderate risk of bias except three studies with low, and one study with high risk of bias (9-15). The study with a high risk of bias score failed to use a control and did not reveal any information about the operator. Furthermore, information about sample size and standardized sample preparation were considered vague by both authors. However, the paper met the inclusion criteria considered by the authors; hence it was included in order not to withhold any relevant information.

Inter-rater Reliability Results

The results of IRR tests for each risk of bias parameter are shown in Table 2. All parameters showed at least 74% or higher in percent user agreement and the average percent user agreement across all five parameters was 89.06%. The average percent of data that are reliable, as determined by Cohen’s Kappa Test, is 46.6%, indicating an overall moderate level of reliability. Because the risk of bias test included 3 different possible scores, the discrepancies between authors were due to whether the parameters in question were clearly specified in the studies. Therefore, most of the score differences were due to one author judging an article as clearly reporting the parameter, while the other author judged the article as vaguely or insufficiently reporting the parameter. This was highlighted with the sample size parameter, in which the authors initially disagreed on whether the details surrounding the sample size were elaborated sufficiently. Another parameter with a low level of agreement was indicated was the standardized sample preparation. The disagreements among the authors regarding this parameter were explained by the variability in extent to which each article specifically stated that they conducted a standardized procedure. All disagreements were resolved after discussion among the authors.

Discussion

Thirty-five in vitro studies and randomized control trials were evaluated to assess the effects of zeolite on the antimicrobial and/or mechanical properties of dental materials. Generally, zeolite itself had little to no effect on antimicrobial properties unless there was an incorporation of ions such as silver or zinc. In addition, ion-incorporated zeolite exhibited prolonged ion release and can serve as a long-term antimicrobial material (4, 10-12). The present systematic review evaluates such properties by grouping the literature into four major categories based on the type of dental material tested: dental restorations, endodontics, prosthetics, and implants.

Dental Restorations

Regarding dental restorative materials, zeolite was generally combined with glass ionomer cements (GIC), resin cements, or bonding agents (3, 13-23).

Glass Ionomer Cement

When an ion-incorporated zeolite was combined with GIC, the antimicrobial effects were usually measured by an in vitro ion release profile or an agar diffusion test. As the ratio of AgZ by weight was increased, the inhibitory effect towards oral bacteria such as S. mutans would also increase (13). Similarly, 2% AgZ had the greatest antimicrobial properties against S. milleri, S. aureus, and E. faecalis compared to 0.2% and 0% AgZ (14). It is important to note that while GIC alone can only provide a rapid release of fluoride for two days; AgZ GIC can provide sustained release of silver ions for long periods of time (13). Similar antimicrobial results to AgZ can also be found in zinc-incorporated zeolite (ZnZ) against E. coli, S. aureus, P. aureginosa, B. subtilis, and C. albicans (15). In addition, zeolite in GIC can also have effective antimicrobial properties against S. mutans when it is loaded with chlorhexidine (16). For GIC used as root canal sealers, the antimicrobial effectiveness against E. faecalis had mixed results (17, 18). ZUT, a combination of 0.2% AgZ by weight (wt) and a GIC sealer, KT-308, inhibited E. faecalis growth significantly more than KT-308 alone, regardless of concentration and time (17). On the other hand, Padachey et al. and McDougall et al. both concluded that ZUT was not more effective than the other GIC (18, 19). The present results show that depending on the concentration of zeolite incorporated, GIC can have enhanced and sustained antimicrobial properties. However, the results may be affected by the use and type of GIC, and this could be a topic of further research.

Although the antimicrobial properties of GIC tended to have a direct relationship with the concentration of zeolite, the amount of zeolite that GIC can successfully uptake is limited by its resulting mechanical properties. The change in shear bond strength of zeolite-incorporated GIC depended on the type and use of the GIC (20, 21). ZUT presented higher shear bond strength than GIC Ketac-Endo alone and was not affected when it was conditioned by media such as calcium hydroxide, chlorhexidine, formocresol, and deionized water (20). However, adding zeolite to provisional cements may decrease the shear bond strength between the dentin and composite resin. Zeolite provisional cement was compared against bone hydroxyapatite provisional cement and showed an inferior bonding strength. A possible explanation for the decrease is that zeolite-incorporated provisional cement may contain more calcium hydroxide than the bone hydroxyapatite-incorporated cement (21). The compressive strength of zeolite-GIC also had varying results depending on the type and use of zeolite (13, 16). Lee et al. reported that although AgZ GIC showed higher compressive strength at 1% wt, it decreased when the concentration was higher than 3% (13). However, Kim et al. concluded that there was no significant difference in compressive or bond strength when small amounts of chlorhexidine-loaded zeolite nanoparticles (around 1% wt) were added to GIC (16).

Resin Cements

When zeolite was incorporated into resins, antimicrobial properties were improved against some microorganisms. Various ratios of AgZ and ZnZ inhibited S. mutans and S. mitis growth but did not inhibit S. salivarius or S. sanguis colonies. In contrast to what was observed with GIC, greater amounts of Ag-Zn-zeolite did not lead to greater amounts of antimicrobial activity in resins (3). After zeolite was modified with active diazonium, the compressive strength and flexural strength of the modified resin-based composite was either improved or remained the same (22). However, further research may be needed in this aspect of modifying zeolite because there is limited research on this topic.

Bonding Agents

Although zeolite alone did not improve the antimicrobial properties of bonding agents, the incorporation of AgZ did. Increasing the exchange time between AgZ and environmental ions can decrease biofilm formation of S. mutans, S. gordonii, and S. sanguinis on dental adhesives. Despite the linear relationship, increasing the amount of silver ions loaded into the zeolite so that the release time is greater than 40 minutes can result in damages to zeolite pore channels and uncontrollable silver ion release (23). Pretreating dentin with zinc zeolite may also enhance the shear bond strength between dentin and alloys using dental adhesives. This increase in shear bond strength was especially significant in the self-etch adhesive approach (24).

Endodontics

Zeolite in endodontics was generally added to calcium hydroxide and mineral trioxide aggregate (MTA) and used as root canal irrigants (25-31).

Root Canal Irrigants

Although 2% AgZ did show statistically significant antimicrobial effectiveness as a root canal irrigant compared to the saline control, it did not exhibit as much effectiveness compared to common root canal irrigants such as 5% Sodium hypochlorite, 2% Chlorhexidine, and 0.10% Octenidine (OCT) (25). A possible reason why AgZ was not as effective as the other root canal irrigants against E. faecalis, C. albicans, and S. aureus growth is that it was not as effective at breaking down the biofilm of these microorganisms (25). When further studies on the mechanical properties of AgZ are published, a better conclusion can be drawn on whether it is worth using AgZ as a root canal irrigant.

Calcium hydroxide

Calcium hydroxide is considered an ideal intracanal medication in endodontics due to its unique ability to increase surrounding pH by dissociating in water to produce hydroxyl ions. Although the high pH denatures bacterial protein and breaks down cell walls, calcium hydroxide was not effective on all types of microorganisms that cause endodontic infections. Ghatole et al. showed that when AgZ was added to calcium hydroxide, antimicrobial property against E. faecalis is enhanced compared to the control or when chlorhexidine is added (26). Therefore, AgZ can potentially be added to intracanal medications, such as calcium hydroxide, to improve antimicrobial effectiveness.

MTA

When AgZ was added to MTA, it exhibited significant antimicrobial properties toward selected oral microflora. AgZ in MTA was effective against most oral microorganisms, such as E. faecalis, S. aureus, and C. albicans. However, it was not effective against P. intermedia and A. israelii (27, 28). No big differences were found in the types of microbes inhibited by 0.2% and 2% AgZ MTA, but 2% AgZ MTA demonstrated significantly higher inhibitory effects than 0.2% AgZ MTA throughout a 72-hour period. Specifically, 2% AgZ demonstrated the highest amount of silver ion release at 24 hours (27). In addition, 2% AgZ was found to have greater antimicrobial properties compared to MTA with 2% chlorhexidine (28). Therefore, 2% AgZ could serve as a potential additive in MTA to enhance its antimicrobial properties.

Although zeolite significantly increased the antimicrobial properties of MTA, it did negatively affect physical properties such as setting time, water absorption, push-out bond strength and compressive strength (29-31). Setting time decreased as the ratio of 2% AgZ increased, and water absorption was the lowest when 2% AgZ was incorporated into MTA compared to the MTA-only control (29). In addition, adding Ag-Zn-Ze composite had a negative effect on the push-out bond strength and compressive strength of MTA (30, 31). A possible reason for the decrease in push-out bond strength is that zeolite is very porous in its structure. When water molecules reside in the pores, they can disturb the hydration and crystallization processes of MTA (30). In conclusion, although zeolite may enhance the antimicrobial properties of MTA, it does reduce the mechanical properties. Thus, further research is needed to determine the proper concentration of zeolite that may be incorporated into MTA, if any, to improve its antimicrobial properties without compromising its mechanical properties.

Prosthesis

Zeolite in prosthesis was added to both acrylic resin and non-acrylic materials, such as ceramic (32-38).

Non-Acrylic Resins

The non-acrylic materials that were tested with zeolite ranged from soft prosthetic liners to all-ceramic prosthesis. Adding AgZ to soft liners improved its antimicrobial properties against C. albicans and gram-negative bacteria while also retaining its viscoelastic properties (32). Regarding the mechanical properties, the applications of zeolite into ceramic prosthesis generally focused on sodalite zeolite (33-36), a subtype of zeolite that can easily infiltrate other material due to its selectivity and strong catalytic activity (33). In alumina and zirconium toughened alumina (ZTA) ceramic prostheses, sodalite zeolite-infiltrated samples had higher bond strength than the commercial glass-infiltrated samples between ceramic core and porcelain (34). In addition, all sodalite zeolite-infiltrated samples showed flexural strength above the acceptable ranges considered by the ISO (35, 36). Furthermore, some studies have shown that the zeolite-infiltrated samples had a significantly higher flexural strength and hardness in comparison with glass-infiltrated control, especially when heated to 1600°C (35). Finally, sodalite zeolite-infiltrated ZTA has one of the highest fracture toughness and elastic modulus values compared to its glass-infiltrated counterparts (33). Therefore, sodalite zeolite infiltrated samples can serve as a potential alternative to the glass infiltrated ZTA due to superior properties in bond strength, flexural strength, Vickers hardness, fracture toughness, and elastic modulus (33-36).

Acrylic Resin

AgZ increased the antimicrobial properties of acrylic resin against oral microbes such as S. mutans, F. nucleatum, and C. albicans. Self-cured acrylic resins tend to absorb copious amounts of water and do not easily polymerize, resulting in the accumulation of periodontal disease-causing bacteria. AgZ-incorporated acrylic resin may potentially resolve this issue since it effectively diminished the attachment of S. mutans, F. nucleatum, and C. albicans to polymethylmethacrylate (PMMA) and lasted for up to 45-60 days (37-39). Similarly, 2.5% Ag-Zn-Ze was effective at inhibiting C. albicans and S. mutans when added to PMMA (40). Therefore, both AgZ and Ag-Zn-Ze may be potentially viable options to improve the antimicrobial properties of PMMA.

However, depending on the percentage added, AgZ may negatively affect the mechanical properties of acrylic resin (38-41). Adding AgZ with concentrations of 2.5% and higher, depending on the type of acrylic resin, will significantly reduce the impact and flexural strength (38, 40, 41). However, some types of heat-cured acrylic resin, such as QC20 and Lucitone 550, may still satisfy the standard for denture acrylics, which requires flexural strength to be higher than 65 MPa (38, 40). Depending on the concentration of zeolite added, both mean tensile strength and bending strength decreased. It was recommended to add less than 4% zeolite wt to keep adequate mechanical strength, and 2% when factoring in both mechanical and fungicidal effects (39). Therefore, low percentages of silver-zinc antimicrobial zeolites added to polymethylmethacrylate can be a valuable alternative for antimicrobial effects, which could help prevent common oral infections such as denture stomatitis (38).

Implants

Numerous applications of zeolite also extend to antibacterial coatings on implants. Although there is not a great amount of literature on this topic, coating titanium implants with AgZ was effective in inhibiting methicillin-resistant S. aureus (MRSA) growth (42). This positive outcome, combined with zeolite’s superior biocompatibility, may render zeolite a possible new material to be used in orthopedic implants.

Limitations of the study

Since most of the literature covered in the present review consisted of in vitro studies, it is important to note that there is a lack of widely accepted and clear criteria for assessing the risk of bias and quality of in vitro studies. To address this problem, a risk of bias test used in a previous study was adapted and used in this review (7). In the future, there should be more in vivo studies performed in order to better understand the effects of zeolite on the oral environment.

Conclusion

The available evidence collected through the present systematic review showed that ion-incorporated zeolite demonstrated enhanced antimicrobial properties when incorporated into dental materials. When ion-zeolite was incorporated into non-acrylic prosthetic materials, the mechanical as well as the antimicrobial properties were enhanced. GIC demonstrated the greatest antimicrobial effectiveness with 2% zeolite wt while maintaining mechanical properties between 1-3% zeolite wt. Therefore, it was recommended to use a concentration of 2% zeolite wt with GIC to optimize both factors. Lower concentrations such as 0.2-2% wt were recommended for MTA and acrylic prosthetic materials, which showed the greatest decrease in mechanical properties when combined with zeolite.