CURSO DE ANÁLISE DE VIBRAÇÕES - FUPAI
(Parte 1 de 4)
dental materials 24 (2008) 149–164 available at w.sciencedirect.com
journal homepage: w.intl.elsevierhealth.com/journals/dema
Mineral trioxide aggregate material use in endodontic treatment: A review of the literature
Howard W. Robertsa,∗, Jeffrey M. Tothb, David W. Berzinsc, David G. Charltond a USAF Dental Evaluation and Consultation Service, Dental Biomaterials Evaluation, Great Lakes, IL, United States b Medical College of Wisconsin, Department of Orthopedics; Marquette University School of Dentistry, Graduate Dental Biomaterials; Milwaukee WI, USA c Marquette University School of Dentistry, Graduate Dental Biomaterials; Milwaukee WI, USA d US Navy Institute for Dental and Biomedical Research, Great Lakes IL, USA article info
Article history: Received 26 July 2005 Received in revised form 23 April 2007 Accepted 30 April 2007
Keywords: Hydroxyapatite Portland cement Biocompatibility Pulp-capping Apexiﬁcation Root-end ﬁlling Pulpotomy Endodontics GMTA WMTA MTA Mineral trioxide aggregate abstract
Objective. The purpose of this paper was to review the composition, properties, biocompatibility, and the clinical results involving the use of mineral trioxide aggregate (MTA) materials in endodontic treatment. Methods. Electronic search of scientiﬁc papers from January 1990 to August 2006 was accomplished using PubMed and Scopus search engines (search terms: MTA, GMTA, WMTA, mineral AND trioxide AND aggregate). Results.Selectedexclusioncriteriaresultedin156citationsfromthescientiﬁc,peer-reviewed dental literature. MTA materials are derived from a Portland cement parent compound and have been demonstrated to be biocompatible endodontic repair materials, with its biocompatible nature strongly suggested by its ability to form hydroxyappatite when exposed to physiologic solutions. With some exceptions, MTA materials provide better microleakage protection than traditional endodontic repair materials using dye, ﬂuid ﬁltration, and bacterial penetration leakage models. In both animal and human studies, MTA materials have been shown to have excellent potential as pulp-capping and pulpotomy medicaments but studieswithlong-termfollow-uparelimited.PreliminarystudiessuggestedafavorableMTA material use as apical and furcation restorative materials as well as medicaments for apexogenesis and apexiﬁcation treatments; however, long-term clinical studies are needed in these areas. Conclusion. MTA materials have been shown to have a biocompatible nature and have excellent potential in endodontic use. MTA materials are a reﬁned Portland cement material and the substitution of Portland cement for MTA products is presently discouraged. Existing human studies involving MTA materials are very promising, however, insufﬁcient randomized, double-blind clinical studies of sufﬁcient duration exist involving MTA for all of its clinical indications. Further clinical studies are needed in these areas. © 2007 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
None of the authors have any ﬁnancial interests in any of the products mentioned in this manuscript. The opinions stated in this manuscript are solely those of the authors and do not represent the opinion of the United States Air Force, the United States Navy, the Department of Defense, or the United States Government. ∗ Corresponding author. Present address: 310C B Street, Building 1H, Great Lakes, IL 60088, USA. Tel.: +1 847 688 7670; fax: +1 847 688 7667.
E-mail address: Howard.email@example.com (H.W. Roberts). 0109-5641/$ – see front matter © 2007 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
|2. Chemical, physical, and mechanical properties||150|
|3. Microleakage studies||153|
|3.1. In vitro dye/ﬂuid ﬁltration method leakage studies||153|
|3.2. In vitro bacterial leakage studies||153|
|3.3. Biocompatibility studies||154|
|3.3.1. In vitro studies||154|
|3.3.2. In vivo studies||155|
|3.4. Characterization of MTA biocompatibility||156|
|4. Clinical applications of mineral trioxide aggregate materials||157|
|4.1.1. Animal models||157|
|4.2. Human studies||157|
|4.2.2. Pulpotomy dressing||157|
|4.2.3. Other MTA material use||159|
It is estimated that over 24 million endodontic procedures are performed on an annual basis, with up to 5.5% of those procedures involving endodontic apical surgery, perforation repair, and apexiﬁcation treatment . Endodontic surgery is performed to resolve inﬂammatory processes that cannot be successfully treated by conventional techniques, which may be due to complex canal and/or apical anatomy and external inﬂammatory processes . Surgical procedures may also be indicated for the resolution of procedural misadventures, to include root perforation that may occur either during canal instrumentation or post-space preparation [2,3]. Surgical treatment usually involves the placement of a material designed to seal the root canal contents from the periradicular tissues and repair root defects . Understandably, this material should demonstrate the ability to form a seal withdentaltissueswhilealsoexhibitingbiocompatiblebehavior with the periodontal tissues .
Anidealendodonticrepairmaterialideallywouldadhereto tooth structure, maintain a sufﬁcient seal, be insoluble in tissue ﬂuids, dimensionally stable, non-resorbable, radiopaque, andexhibitbiocompatibilityifnotbioactivity[2,4,5].Anumber of materials have historically been used for retrograde ﬁllings and perforation repair, such as amalgam, zinc-oxide-eugenol cements, composite resin, and glass-ionomer cements [4,6]. Unfortunately, none of these materials have been able to satisfy the total requirements of an ideal material [4,5].
Mineral trioxide aggregate (MTA) is a biomaterial that has been investigated for endodontic applications since the early 1990s. MTA was ﬁrst described in the dental scientiﬁc literature in 1993  and was given approval for endodontic use by the U.S. Food and Drug Administration in 1998 .A si t will soon follow, MTA materials are derived from a Portland cementparentcompound:itisinterestingthatnoinformation has been published regarding to any investigations that led to the precise delineation of the present MTA materials. The aim of this article is to present a systematic review of the physical properties, biocompatibility testing, and pertinent clinical studies involving MTA materials.
A structured literature review was performed for articles published between January 1990 and August 2006. The Internet database PubMed (w.ncbi.nlm.nih.gov/entrez) and Scopus (w.scopus.com) was used to search for the keywords MTA, GMTA, WMTA, and mineral AND trioxide AND aggregate. For further reﬁnement, the following exclusion criteria were deﬁned: Publications were limited to those of English language and from the scientiﬁc, peer-reviewed literature. Furthermore, publications possessing a questionable peer-review process (e.g., manufacturer-supported) were excluded for consideration. Although clinical case reports were included, only clinical studies involving appropriate number, sufﬁcient controls and analysis were given serious consideration . Using the search keywords limited to dental publications produced a total of 245 results, of which application of inclusion criteria produced the 156 citations that forms the basis for this review (Fig. 1).
2. Chemical, physical, and mechanical properties
MTA materials are a mixture of a reﬁned Portland cement and bismuth oxide, and are reported to contain trace amounts icate, tricalcium silicate, tricalcium aluminate, gypsum, and tetracalcium aluminoferrite [10–12]. Gypsum is an important determinantofsettingtime,asistetracalciumaluminoferrate, although to a lesser extent . MTA products may contain approximatelyhalfthegypsumcontentofPortlandcement,as wellassmalleramountsofaluminumspecies,whichprovides a longer working time than Portland cement. Although it may be inferred that Portland cement could serve as a MTA substi-
Fig. 1 – Literature search criteria.
tute, it is important to emphasize Portland cement and MTA are not identical materials. MTA products have been reported tohaveasmallermeanparticlesize,containfewertoxicheavy metals,hasalongerworkingtime,andappearstohaveundergone additional processing/puriﬁcation than regular Portland cements [13,14].
The ﬁrst MTA material was described as a ﬁne hydrophilic powder composed predominantly of calcium and phosphorus ions, with added bismuth oxide to provide radiopacity greater thandentin.However,laterinvestigations[10,1,16]found phosphorus levels in MTA products to be very low, near electron probe microanalysis detection limit, which correlates with the manufacturer’s material safety data sheet . Since it is unlikely that a signiﬁcant compositional change in MTA materials occurred from the time of the ﬁrst report and given that Portland cement is primarily composed of silicate and aluminate materials [10,13,18,19] earlier reports  of MTA product phosphorus content are most likely in error .
The MTA product powder is mixed with supplied sterile water in a 3:1 powder/liquid ratio and it is recommended that a moist cotton pellet be temporarily placed in direct contact withthematerialandleftuntilafollow-upappointment.Upon hydration, MTA materials form a colloidal gel that solidiﬁes to a hard structure in approximately 3–4h [12,15], with moisture from the surrounding tissues purportedly assisting the set- ting reaction . Hydrated MTA products have an initial pH of 10.2, which rises to 12.5 three hours after mixing [1,15]. The setting process is described as a hydration reaction of trical- cium silicate (3CaO·SiO2) and dicalcium silicate (2CaO·SiO2), which the latter is said to be responsible for the development of material strength . Although weaker than other materials used for similar purposes, MTA compressive strength has been reported to increase in the presence of moisture for up to 21 days , while MTA product microhardness and hydration behavior has been reported to be adversely affected with exposure to the pH range of inﬂammatory environments (pH 5) as compared to physiologic conditions (pH 7) .
MTA materials have been reported to solidify similar to other mineral cements, in which the anhydrous material dissolves, followed by the crystallization of hydrates in an interlocking mass . The basic framework of the hydrated mass is formed by the interlocking of cubic and needle-like crystals in which the needle-like crystals form in sharply delineatedthickbundlesthatﬁlltheinter-grainspacebetween the cubic crystals . The effect of mixing MTA powder with different liquids and additives has shown that the choice of preparationliquidcanhaveaneffectonsettingtimeandcompressive strength . Three and ﬁve percent calcium chloride solutions, a water-based lubricant, and sodium hypochlorite gels decreased setting time; however ﬁnal compressive strength was signiﬁcantly lower than that obtained prepared with sterile water. Preparation with saline and 2% lidocaine anesthetic solution increased setting time; but compressive strength was not signiﬁcantly affected. Interestingly, a MTA product prepared with chlorhexidine gluconate gel did not set . It seems to reason that the setting reaction of MTA products,likeitsPortlandcementparentcompound,isahydration reaction;sufﬁcientwaterinpotentialpreparationliquidsmust be present for reaction . Furthermore, it should also be intuitive that the chosen preparation liquid must also possess water with the necessary diffusion ability to be available for the hydration reaction. Clinicians may consider different solutions instead of sterile water in the preparation of MTA materials; however, clinicians should consider the potential therapeutic gain versus the loss of MTA material physical properties in these situations.
Up to 2002, only one MTA material consisting of graycolored powder was available, and in that year white mineral trioxide aggregate (WMTA) was introduced as ProRoot MTA (Dentsply Endodontics, Tulsa, OK, USA) to address esthetic concerns . After that time, two forms of MTA materials were categorized: the traditional gray MTA (GMTA) and WMTA. Scanning electron microscopy (SEM) and electron probe microanalysis characterized the differences between GMTA and WMTA and found that the major difference between GMTA and WMTA is in the concentrations of Al2O3, MgO,andFeO[12,16](Table1).WMTAwasfoundtohave54.9% less Al2O3, 56.5% less MgO, and 90.8% less FeO, which leads to the conclusion that the FeO reduction is most likely the cause for the color change . WMTA was also reported to possess an overall smaller particle size than GMTA  while it was also suggested the reduction in magnesium could also contribute to the lighter color of WMTA . A reported elemental analysis comparing a commercial form of WMTA, a Portland cement,andthestatedMTApatentcanbeobservedinTable2.
Table 1 – Chemical compositions of GMTA and WMTA (wt%)
Chemical WMTA GMTA
Adapted from Asgary et al. .
X-ray photoelectron spectroscopy (XPS) that reported surface sulfur and potassium species increase 3-fold during the setting reaction. This suggested that MTA material setting time could be prolonged by the formation of a passivating trisulfate species layer, which may serve to prevent further hydration and reaction . This trisulfate species may serve a protective function, as it was reported that that WMTA ﬂexural strength was signiﬁcantly reduced when 2-m thick layers wereexposedtosterilesalinemoistureformorethan24h. Calcium release from MTA materials diminishes slightly with time  while MTA materials were reported to form a porous matrix characterized by internal capillaries and water channels in which increased liquid/powder ratio produced more porosity and increased solubility . GMTA solubility levels have been reported to be stable over time, but the usuallyreported pH of between 1 or 12 may slightly decrease . The high pH level of MTA materials has led some to theorize that the biologic activity is due to the formation of calcium hydroxide [2–25]. WMTA solubility, hardness, and radiopacity has been compared to two Portland cements reporting that WMTAwassigniﬁcantlylesssoluble,exhibitedgreaterVickers hardness, and was more radiopaque .
There are some evidence that MTA materials possess a prolonged maturation process that continues past the stated setting time of 3–4h, as GMTA retention strength for furcation repairshasbeenreportedtoresistsigniﬁcantlymoredislodge-
Table 2 – Elemental analysis comparison portland cement and ProRoot WMTA (wt%)
Element Portland cement WMTA Patent
Adapted from Dammaschke et al. .
ment at 72h as compared to 24h . This was corroborated by one study that reported increase push-out strength up to7d ays  with an additional study reporting maximum GMTA push-out strength observed at 21 days . Interestingly, GMTA that has not reached full maturity has been suggested to possess an ability to re-establish dislodgement resistance after partial displacement; but the re-established resistancestrengthdecreasedasdislodgementtimeincreased after placement .
Different intracanal irrigant/oxidizing agents have been found to affect the push-out strength of GMTA as it was susceptibletosodiumhypochlorite,sodiumperboratemixedwith saline, 30% hydrogen peroxide, sodium perborate mixed with 30% hydrogen peroxide, and saline at 7 days . GMTA pushout strength was also reported to be similar to Super-EBA and IRM when exposed to saline or sodium hypochlorite, but GMTA was more susceptible to oxidizing agents , which was reinforced by a report that a hydrogen peroxide-based canal preparatory agent signiﬁcantly reduced the push-out strength of GMTA to dentin, whereas 2% chlorhexidine and 5.25% sodium hypochlorite did not . Another report found thatperforationretentionstrengthwasnotaffectedbypreparing GMTA with either saline, sterile water, or lidocaine, but the bond strength to blood-contaminated root dentin was signiﬁcantly less than that observed to uncontaminated dentin . Any adhesion that may be formed between GMTA and dentin may be stronger than the cohesive strength of the GMTA material, as it was reported that GMTA–dentin bond failures was usually cohesive within the MTA material . Furthermore, total GMTA–dentin bond strength is also heightened by increased surface area, as one report states that 4mm of GMTA has been reported to afford more resistance to displacementthan1-mmthickapplications,andwasnotaffected by previous calcium hydroxide placement .
Placement of GMTA using hand condensation techniques has been suggested to provide less porosity than ultrasonicassistedtechniquesinsimulatedstraightcanals.However, different results were found that suggested a denser MTA ﬁl was obtained in both straight and curved canals with a combination hand and ultrasonic placement over a solely manual condensation technique . GMTA root-end marginal adaptation and stability was reported to be signiﬁcantly better than a ZOE preparation after being submitted to a computer controlled, simulated masticating apparatus that produced an estimated 5 year equivalence of chewing cycles .P refabricated posts luted with GMTA were reported to provide signiﬁcantly less retentive strength than a glass-ionomer and zinc phosphate luting agents . WMTA has been reported to strengthen the cervical fracture resistance of immature sheep incisors as compared to the use of calcium hydroxide . Although this result is considered promising, it should be noted that within the groups sample number were low (<10) and the sample dimensions were also varied in dimension.
WMTA and a ZOE preparation was found to have similar antibacterial properties against Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa in a direct contact test  while substituting 0.12% chlorhexidine gluconate provided more antibacterial activity against Actinomyces odontolyticus, Fusobacterium nucleatum, Streptococcus sanguis, E. faecalis, Escherichia coli, S. aureus, P. aeruginosa, and Candida albicans than WMTA prepared with sterile water alone . This ﬁnding should be tempered with knowledge that MTA materials may not set when mixed with some chlorhexidine preparations . Both freshly mixed and set GMTA was reported to be inhibitory to C. albicans using an antifungal tube-dilution method  while another study reported differences in that GMTA and WMTA at different powder/liquid mixtures were not equally effective at preventing the growth of C. albicans . Both WMTA and GMTA in concentrations of 50 and 25mg/ml were equally inhibitive against C. albicans for upto7days;however,atlowerconcentrationsonlyGMTAwas effective . This is evidence of not only the importance of proper powder/liquid ratios but also raises possible questions concerning that the two MTA preparations may not be equally effective in some clinical applications.
In conclusion, MTA materials are derived from Portland cement, and although it could be inferred that Portland cement could serve as a suitable substitute, it is important to emphasize that MTA products and Portland cement are not identical materials. MTA materials have been reported to have a smaller mean particle size, contain less heavy metals, have a longer working time, and appears to have undergone additional processing/puriﬁcation than the Portland cement parent compound. WMTA has been marketed since 2002 due to esthetic considerations and contains less iron, aluminum, andmagnesiumoxidesthanitsGMTAcounterpart.Bothmaterials undergo a hydration setting reaction that is said to reach an initial set in 3–4h but whose maturation and resistance to dislodgement increases with time. The physical properties and setting time of MTA materials can be affected by different preparation liquids and both WMTA and GMTA have been shown to possess antibacterial and antifungal activity, which is presumably due to its pH.
3. Microleakage studies
The success of an endodontic material may largely depend on its sealing ability, as most post-treatment endodontic disease is thought to occur due to tissue and other materials in uncleaned and/or unobturated areas of the root canal system that egress into the surrounding tissues .
3.1. In vitro dye/ﬂuid ﬁltration method leakage studies
The microleakage of MTA materials compared to other traditional endodontic materials via in vitro dye and ﬂuid ﬁltration methods have been the subject of many studies [42–64]. GMTA has been reported to have less microleakage than amalgam [42–45,47,48,51,52], zinc-oxide-eugenol (ZOE) preparations [42–4], and a conventional glass-ionomer material  when used as a root-end restoration following apical resection. However, other studies reported no difference in leakage between MTA materials and zinc-oxide-eugenol preparations [45,51,52,59], and conventional glass-ionomer restorative materials . The minimal thickness for MTA to effectively seal the apical area has been investigated with one study reporting a placement thickness of at least 3mm  with another report stating a minimal of 4mm is required for signiﬁcant microleakage prevention . The addition of calcium chloride has been reported to enhance the sealing ability of both GMTA and WMTA, probablyby the effect of calcium chloride’s enhancement of MTA material setting time . WMTA and GMTA have been compared for the sealing of simulated canals with open apices using thicknesses of 2 and 5mm followed by gutta percha obturation either immediately after MTA material placement or 24h later . Results found that GMTA had less microleakage than WMTA in samples obturated 24h after MTA placement; in all groups 5mm of MTA material allowed less leakage. Based on the results, theauthorsrecommendeda5-mmGMTAapicalbarrierplaced for treatment of open apices with gutta percha obturation followed24hlater.Visualtopographyevaluationsofroot-end restorationsrestoredwithGMTA,ZOEmaterials,andamalgam have reported that root-end restoration ﬁnishing method had no effect on marginal adaptation of GMTA and ZOE material  while another report stated that GMTA appeared to have better root-end marginal adaptation than amalgam .
For repair of furcation perforations, a ZOE preparation was reported to provide a better seal than GMTA at 24h, after which no difference in leakage was observed . However, in another report, GMTA was found to allow more microleakage in furcation repairs when compared to a ZOE preparation and a self-etch, one step bonding agent . The furcation perforationrepairmicroleakageofGMTAandWMTAwascompared from both an orthograde and retrograde direction . The results found no difference in leakage between the two MTA materials; but the more interesting ﬁndings were that signiﬁcantly more leakage was found from a microleakage challenge from an orthograde direction . This suggests an impelling need for an adequate coronal barrier material over MTA furcation repairs to adequately protect against coronal microleakage.
The microleakage of MTA materials used for root canal obturation has been reported by two studies [54,61]. The ﬁrst studysuggestedthatGMTAdisplayedmoremicroleakagethan laterally-condensed as well as thermoplasticized gutta percha  but this was contrasted by the other study which reported that both WMTA and GMTA allowed less apical microleakage than warm, vertically condensed gutta percha . The second study also reported no signiﬁcant difference in leakage between GMTA and WMTA, but importantly noted that root canal obturation with MTA materials would severely limit retreatment options and should be considered in only select cases . Another report reported that root resection of canals obturated with GMTA did not affect its sealing ability .
3.2. In vitro bacterial leakage studies
The microleakage of MTA materials has also been evaluated, to a lesser extent, using bacterial penetration methods [31,41,65–75]. GMTA has been evaluated for resistance against apical bacterial leakage when utilized as a root-end ﬁlling compared with amalgam and ZOE materials within endodontically prepared but unobturated root canals inoculated with Staphylococcus epidermis  and Serratia marcescens .G MTA was found to have signiﬁcantly more resistance to S. epidermis penetration than amalgam and ZOE preparations with no leakageevidentafter90days,withtheothermaterialsexhibit- ing bacterial penetration ranging from 6 to 57 days . The second study found that GMTA resisted S. macescens penetrationforupto49daysafterinoculationwhiletheamalgamand ZOE materials displayed trends for more bacterial penetration .WMTAandabondedpolymer-basedmaterialwerefound to exhibit similar root-end bacterial leakage resistance using a Streptococcus salivarius model with both materials having signiﬁcantly less bacterial leakage than a ZOE preparation . GMTA was also reported to allow signiﬁcantly less E. coli endotoxinpenetrationusingamodiﬁedLimulusAmebocyteLysate test than amalgam and two ZOE preparations over a 12-week evaluation .
In contrast, GMTA was found to have the same bacterial penetration resistance as a ZOE preparation, amalgam, a bonded resin composite, as well as a bonded amalgam during a 12-week evaluation using Streptococcus salivarius . Similar results were reported during a 47-day study with GMTA compared against a polyacid-modiﬁed resin composite and a ZOE preparation using Prevotella nigrescens . Furthermore, WMTA root-end ﬁllings contaminated with either blood, saline, or saliva during placement were found to displayvaryingresistancetoStaphylococcusepidermidiswithsaliva contamination causing signiﬁcantly more leakage .
When used as perforation repair materials, GMTA did not demonstrate any bacterial leakage during a 45-day evaluation while approximately half of the amalgam-repaired furcations allowed penetration and transmission of F. nucleatum . Furthermore, no signiﬁcant difference was found between GMTA and WMTA in the resistance to F. nucleatum penetration when used for furcation repair . When used in the treatment of immature apices, GMTA has been reported to provide resistance to bacterial penetration by E. faecalis and S. epidermis but not Enterobacter aerogenes . A similar report reinforced GMTA resistance to E. faecalis penetration with no leakage identiﬁed by E. faecalis 16S rDNA polymerase chain reaction assay after 10 days . GMTA was also evaluated against Actinomyces viscosus microleakage for up to 70 days in simulated imature apices that had received either a 2- or 5-m apical GMTA restoration, or a series of 2-m GMTA apical retrograde ﬁllings. Results reported that only the 5-m thick restoration resisted microleakage for the entire evaluation, and exhibited signiﬁcantly less leakage compared to the positive control and other GMTA groups . When evaluated as a coronal barrier, no difference against human saliva bacterial penetration was found between GMTA, WMTA, or a resin-modiﬁed glass-ionomer restorative material . One study attempted to evaluate the in vivo coronal sealing ability of WMTA in canineendodonticallypreparedandobturatedrootcanals,but no conclusive results were found .
In conclusion, MTA materials have been investigated using dye, ﬂuid ﬁltration and bacterial inﬁltration leakage methods. The majority of the dye and ﬂuid ﬁltration studies suggest that MTA materials overall allow less microleakage than traditional materials when used as an apical restoration while providing equivalent protection as a ZOE preparation when used to repair furcation perforations. GMTA and WMTA were shown to provide equivocal results compared against gutta percha when used as a root canal obturation material in the limited number of microleakage studies. MTA materials have been suggested to afford less microleakage than traditional materials in a majority of bacteria-based microleakage studies when used as an apical restoration, furcation repair, and in the treatment of immature apices. In both ﬂuid ﬁltration and bacterial leakage models, 3mm of MTA material is suggested as the minimal amount for protection against microleakage while 5mm is suggested in the treatment of immature apices.
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