Methodology

An electronic search of scientific papers was accomplished using PubMed and MedLine search engines and Cochrane databases using selected keywords and with appropriate medical subject headings (MeSH). The search terms (keywords/headings) used were: mineral trioxide aggregate (MTA); White MTA (WMTA); Gray MTA (GMTA); MTA Angelus (AMTA); Portland cement (PC); properties of MTA (physical, chemical, bacterial, biological, biocompatibility); pulp capping agents; retro-filling materials; perforation repairs (lateral and furcation); root-end filling materials; recent advances in endodontic materials; newer obturation materials; apexogenesis; and apexification. Only articles relevant to the topic (MTA) and published in English in peer-reviewed journals from January 1991 to May 2010 were included. Following this, a hand-search was conducted for the available issues of all the major journals pertaining to the topic.

Composition

MTA is an ash-colored powder made up of fine hydrophilic particles.^6,10 Available as Gray MTA (GMTA) and White MTA (WMTA), both formulae basically are 75% Portland cement, 20% bismuth oxide, and 5% gypsum (Ca) by weight.^11,12 Thus, MTA is a mixture of a refined Portland cement and bismuth oxide (17% to 18%) with trace amounts of SiO2, CaO MgO, K2SO4, and Na2SO4.^5,13 Bismuth oxide is added to make the material radiopaque. Bismuth affects calcium hydroxide precipitation after MTA hydration; and under acidic conditions (inflammation), bismuth oxide can be released in the environment decreasing MTA’s biocompatibility as it inhibits cell proliferation.^14,15 Gray MTA (GMTA) principally consists of tricalcium silicate, dicalcium silicate, tricalcium oxide, tricalcium aluminate, tetracalcium aluminoferrite, calcium sulphate, silicate oxide, and bismuth oxide,^12,13 with a predominance of calcium and phosphorus ions (as per earlier reports).¹⁶ However, recent investigations using electron probe microanalysis suggested that phosphorus levels in MTA products are very low.^17,18 White MTA (WMTA) basically lacks the tetracalcium aluminoferrite component with a lesser quantity/content of iron, aluminium, and magnesium oxides.^12,17 Another commercially available MTA material is MTA-Angelus, which is 80% Portland cement and 20% bismuth oxide, and is more radiopaque than GMTA.¹²

Manipulation and Setting

MTA is available either as a box of five 1-gram single-use packets or as premeasured water packs for easy manipulation and application. ProRoot liquid microampules (sterile water) and a carrier are also provided with the packet. It should be stored in closed sealed containers away from moisture.^5,10

The powder is mixed with supplied sterile water in a 3:1 powder/liquid ratio. A paper pad or a glass slab and a plastic or a metal spatula is used to mix the material to obtain a putty-like consistency. The mixing time should be less than 4 minutes, as prolonged mixing can cause dehydration of the mixture.^10,19 The mixture can be carried with a plastic or metal carrier.²⁰ The unused portion of MTA powder can be stored in sterilized empty film canisters.

MTA is uninhibited by blood or water, as moisture is required for a better setting of the material.²¹ The required hydration for setting is provided by a moist cotton pellet placed temporarily (until the next appointment) in direct contact and/or on the surrounding tissues.²² The hydration reaction during setting occurs between tricalcium silicate (3CaO·SiO2) and dicalcium silicate (2CaO·SiO2) to form a calcium hydroxide and calcium silicate hydrate gel, producing an alkaline pH.^12,20,23 However, Dammaschke et al reported that calcium hydroxide is a product of tricalcium aluminate hydrogenation.^12,24 A further reaction forms a high-sulphate calcium sulphoaluminate during the reaction with tricalcium aluminate and calcium phosphate.²⁵ The released calcium ions diffuse through dentinal tubules, and increase their concentration over time as the material cures.²⁶ Upon hydration, the poorly crystallized and porous solid gel (hydrated forms of components)¹⁴ that is formed solidifies to a hard structure in approximately 3 to 4 hours (initial set), with mean setting time of 165 ± 5 minutes.^8,27,28 Although moisture is needed for setting of the material, excess moisture can result in a soupy mix that is difficult to use.⁵

The hydrated set material consists of interlocked cubic and needle-like crystals. The needle-like crystals exist as sharply delineated thick bundles filling the inter-grain space between the cubic crystals.^13,29 MTA retention and push-out strength increase with time, extending from 72 hours to 21 days, indicating a prolonged maturation process of the material.^10,13,19 This slower setting time may reduce the setting shrinkage, contributing to the low microleakage shown by the material. X-ray photoelectron spectroscopy (XPS) examination of WMTA has reported a threefold increase in surface sulphur and potassium species during the setting reaction.²⁴ Thus, a passivating trisulphate species layer may aid in prolonging the setting time of the material (WMTA) and also serve a protective function.^8,24

Thus, one of the main drawbacks of MTA is the extended setting period and the prolonged maturation phase. Use of different liquids and additives for the manipulation of MTA powder can influence the setting time and compressive strength of the material.^13,30 However, it is imperative that the manipulation liquid have adequate water content with necessary diffusion ability to allow the hydration reaction to occur.¹³ Calcium chloride solutions (3% to 5%) and sodium hypochlorite gels decrease the setting time, whereas saline and 2% lidocaine increase the setting time. Chlorhexidine gluconate affects the surface hardness of MTA (WMTA) during the initial 24 hours.³¹ However, use of calcium chloride and sodium hypochlorite reduce the final compressive strength (as compared to sterile water) with saline and 2% lidocaine, having no significant affect on it.³⁰ Accelerators such as sodium phosphate dibasic (Na₂HPO₄) also reduce the setting time.^5,30

Usually, MTA is pressed into the desired location and not really condensed. The mixture is usually condensed with a moistened cotton pellet using light gentle strokes.⁵ Either hand or ultrasonic instruments can be used for placement and/or condensation of MTA. Hand instruments like Tulsa Carrier (DENTSPLY Tulsa Dental Specialties, www.dentsply.com), amalgam carrier, pluggers, paper points, messing gun MTA carriers, large bore needles, or Lentulo spirals can be used.^5,8,10 In ultrasonic condensation, a hand instrument (condenser) placed in direct contact with MTA is activated by ultrasonics placed in contact with the shaft of the hand instrument. Different results are obtained from different studies regarding the best condensation technique for placement of MTA. Some authors claimed that hand condensation techniques offer less porosity and better adaptation than ultrasonic-assisted techniques^,5,8,32 whereas others suggested that a denser MTA-fill—both in straight and curved-root canals—and better resistance to bacterial penetration is achieved with a combination of hand and ultrasonic techniques.^8,33 Though the amount of condensation pressure did not affect the compressive strength, an increase in condensation pressure can interfere with the ingress of water required to hydrate the cement, which in turn may reduce the surface hardness.^8,34 Also, irrigation should be performed before the placement, because following placement, irrigation can cause significant washout of the material.

Properties

The main characteristic properties of MTA include superior sealing ability, biocompatibility, antimicrobial effect, radiopacity, dimensional stability, and tolerance to moisture over other dental materials such as IRM, amalgam, Ca(OH)2, super EBA, ZOE, etc.^{5,8-10,13,20,35} Thus, MTA has gained popularity among dental practitioners, especially endodontists, in recent times. Among the above-mentioned properties, the sealing ability and biocompatibility of MTA has been studied extensively^9,13 (Figure 1).

Strength

The compressive strength of set MTA is about 70 MPa, which equals IRM and super EBA, but is less than that of amalgam.^10,27 Owing to the low compressive strength, placement of MTA in functional areas should be avoided. MTA’s compressive strength is not significantly affected by condensation pressure.8 As discussed earlier, MTA has a prolonged maturation process, with increased compressive strength, push-out strength, and retention strength of the material with time (up to 21 days) in the presence of moisture. The initial compressive strength following 24 hours is 40 MPa, which increases to 67.3 MPa after 21 days. Thus, after 3 weeks, no significant difference in compressive strength was observed between super EBA, IRM, and MTA.^8,27 A similar increase in flexure and push-out strength was also observed under moist conditions with the passage of time.^36,37 This is because the dicalcium silicate hydration rate is slower than that of tri- calcium silicate.²⁴ Thus, optimal physical properties are gained with time if there is enough moisture following placement at the operation site.^5,8,10

Different intracanal irrigants/oxidizing agents can affect the push-out strength/retention strength of GMTA. Use of saline, sterile water, or lidocaine has no effect on the retention strength of the material. However, it is more susceptible to oxidizing agents such as sodium perborate mixed with saline, 30% hydrogen peroxide, and sodium perborate mixed with 30% hydrogen peroxide, whereas 2% chlorhexidine and 5.25% sodium hypochlorite did not significantly affect the strength.^38,39 Also, the retention strength of the material is affected by blood-contaminated root surfaces (dentin).⁴⁰ Investigations also suggested a significant decrease in compressive strength following phosphoric acid (37%) etching. Therefore, restoration with resin-based composite should be postponed for at least 96 hours following placement of MTA.⁴¹

Retentive Strength and Bond Strength

The retentive strength of MTA is significantly less than that of glass ionomer or zinc phosphate cement and, thus, it is not considered to be a suitable luting agent.⁴² Studies have shown that a 4-mm thickness of MTA (apical barrier) offered more resistance to displacement than a 1-mm thickness,^43,44 as GMTA-dentin bond strength increases with increases in surface area.⁸ A total-etch single-bottle adhesive with a resin-based composite or compomer produced higher bond strength than a single-step self-etch system over MTA.⁴⁵

Microhardness

An exposure to acidic pH (pH5), as observed in inflammatory environment, has an adverse effect on the microhardness of both GMTA and WMTA.²⁹ It is attributed to the absence and growth of needle-like crystals between the cubic crystals during the hydration phase. A 5-mm thickness of MTA is significantly harder than a 2-mm thickness.⁴⁶ Ethylenediaminetetraacetic acid (EDTA), BioPure MTAD (DENTSPLY Tulsa Dental Specialties), and acid-etching produce surface roughness and significantly reduce the microhardness of MTA.^41,47 An increase in condensation pressure results in a more compact mass with fewer micro channels available for water uptake, thus reducing the microhardness of the material.⁸

pH

Hydrated MTA has an initial pH of 10.2, which rises to 12.5 (similar to calcium hydroxide) 3 hours after mixing and following setting.^13,16 The high pH is theorized to be responsible for the antimicrobial action and biological activity of the material. This high pH is attained due to the constant release of calcium from MTA and the formation of Ca(OH)2. The usual pH (11 to 12) of MTA materials decreases slightly with time.⁴⁸

Sealing Ability (Microleakage)

Results obtained from dye leakage, fluid filtration, protein leakage, and bacterial leakage and endotoxin leakage studies (S. epidermis, S. salivaris, S. marcescens, E. coli, F. nucleatum) indicated that overall MTA showed less microleakage and better sealing ability than traditional materials like amalgam, zinc oxide eugenol-based materials, conventional glass-ionomer, gutta-percha, etc., when used for root-end restoration, root canal obturation, furcation repair, and treatment of immature apices.^6,9,13 Expansion of MTA during setting can be responsible for its excellent sealing ability.^18,49 Usually a thickness of 3 mm to 5 mm is sufficient to provide a good seal. In the presence of blood contamination, MTA has also been shown to leak significantly less compared to amalgam, IRM, and super EBA.²¹ No difference in microleakage is reported when used either in an orthograde manner (root-canal filling) or in a retrograde manner (root-end filling).⁵⁰ However, the presence of residual calcium hydroxide, from the prior placement as an intracanal dressing, can interfere with the adaptation and reduce the sealing ability of MTA. It can act as a mechanical obstacle or can chemically react with MTA.⁵¹ In dye leakage investigations, MTA mixed with 10% calcium chloride showed a better sealing ability, with no significant difference in microleakage on addition of chlorhexidine.^52,53

Biocompatibility

Biocompatibility studies in general considered both GMTA and WMTA as biocompatible.^9,54 No genetic damage, genetic mutation, chromosomal breakage, altered DNA repair capacity, or cellular transformation was observed with MTA. MTA has shown to posses neither mutagenic (Ames mutagenicity assay, Salmonella typhimurium) nor genotoxic effects (single cell gel/comet assay).^55,56 Neither freshly mixed nor set MTA displayed neurotoxicity.⁵⁷ It was found to be less cytotoxic than amalgam, super EBA, and IRM, with set MTA being less cytotoxic than fresh MTA.^9,13,54 Enhanced attachment and proliferation of periodontal ligament and gingival fibroblasts were observed on the set-surfaces of MTA.^58,59 Similarly, cell cultures studies (animal and human) using human alveolar bone cells, mouse preosteoblasts, osteoblasts, dentinoblasts, and mouse cementoblasts have shown good survival, proliferation, and attachment, with a faster and better growth of cells on the MTA surface.^9,35,54 MTA has also shown to have a better stimulating effect on human dental pulp cells than a commercial calcium hydroxide preparation. It was proposed that cellular proliferation is via intra- and extracellular Ca2+ and Erk-dependent pathways, and cell survival is via the Pl3K/Akt signaling pathway.³⁵ Animal cells (rat bone marrow cells, mouse preosteoblasts) and human cells (gingival fibroblasts, periodontal ligament fibroblasts, alveolar bone cells) exposed to MTA have been shown to express alkaline phosphatase, bone sialoprotein, periostin, and osteocalcin, along with the formation of extensive collagenous matrix.^60-62 Addition of enamel matrix derivative to MTA has been shown to improve human dental pulp cell differentiation, alkaline phosphatase activity, and mineralization.⁶³ Although addition of chlorhexidine improved the antibacterial properties of MTA, it adversely affected the biocompatibility of the material.⁹

Animal and human studies have shown minimal or no inflammation to bone and connective tissue following implantation of MTA.^9,13 When used (in a canine model) for root-end restoration or for the repair of lateral/furcation perforation, MTA has shown favorable healing characteristics, such as lack of inflammation, no ankylosis, cellular cementum formation (overgrowth), and PDL regeneration between the cementum and alveolar bone.^6,9,13 MTA stimulates cytokine release and interleukin production, which may actively promote hard-tissue formation.^9,64 Shabahang et al observed that MTA induced hard-tissue formation more often than osteogenic protein-1 and Ca(OH)2.⁶⁵

Intra-osseous implantation of MTA showed a relatively mild-to-minor inflammatory response, which is more favorable compared to amalgam, super EBA, and IRM.⁶⁶

Some studies considered that the biocompatibility of MTA is attributable to the release of hydroxyl ions and formation of calcium hydroxide during the hydration process.^23,48 Other reports had observed the formation of a white interfacial material (precipitates) between GMTA and tooth structure within 1 to 2 hours when exposed to physiologic fluids (phosphate-buffered physiologic solution) in vivo or with simulated body fluids in vitro.^18,20 SEM and x-ray diffraction (XRD) analysis of these precipitates revealed the presence of chemically and structurally similar hydroxyapatite (HA)-like structure with a chemical composition of oxygen, calcium, and phosphorus, along with trace amounts of bismuth, silicon, and aluminum.¹⁸ However, the calcium-to-phosphorus ratios reportedly differed from that of natural hydroxyapatite.⁶⁷ This HA-like structure can release calcium and phosphorus continuously, promoting the regeneration and remineralization of hard tissues and increasing the sealing ability of MTA. The HA-layer also creates a chemical bond between MTA and the dentinal walls.⁷ The particle size and dimensional shape of MTA can also occlude dentinal tubules, which might harbor microorganisms.⁶⁸ GMTA has a greater amount of HA-crystal formation than WMTA with the presence of lower levels of silica and phosphorus in GMTA crystals and more calcium ions in WMTA crystals.⁶⁷

Thus, release of hydroxyl ions, a sustained high pH for extended periods, modulation of cytokine production, formation of calcium hydroxide, and a mineralized interstitial layer (HA) may be responsible for the excellent biocompatibility and biological activity of the material.^7,20

Antimicrobial Properties

In vitro studies have shown antibacterial activity of MTA against M. luteus, S. aureus, E. coli, P. aeruginosa, E. faecalis, and S. sanguis.^5,8 A study evaluated the antimicrobial property of MTA, amalgam, and super EBA against nine strict anaerobes. MTA was found to have an antibacterial effect on five of the nine facultative bacteria, but no effect on any of the strict anaerobes.⁶⁹ Thus, the use of MTA as an antibacterial agent may not be very beneficial in endodontic cases. The use of 2% CHX and 0.12% CHX in combination with MTA has been reported to significantly increase the antibacterial effect of both types of MTA.⁷⁰

Al-Nahazan and Al-Judai⁷¹ evaluated the antifungal activity of both freshly mixed and 24-hour-set MTA using a tube dilution test. It was observed that both types were effective against Candida albicans.²⁰ The antifungal effect of MTA might be due to its high pH or to substances that are released from MTA and is dependent on the concentration of MTA; a concentration of 25 mg/mL to 50 mg/mL is required to show an antifungal effect.⁷²

Regenerative Potential and Biological Activity

MTA has the capacity to induce bone, dentin, and cementum formation and regeneration of periapical tissues (periodontal ligament and cementum).^7,8,13 MTA provides a good biological seal and can act as a scaffold for the formation and/or regeneration of hard tissue (periapical). It is an osteoconductive, osteoinductive, and cementogenic (cementoconductive and cementoinductive) agent.^9,20 MTA stimulates immune cells to release lymphokines and bone coupling factors required for the repair and regeneration of cementum and healing of osseous periapical defects.^64,73 MTA can also stimulate periodontal ligament fibroblasts to display osteogenic phenotype and produce osteonectin, osteopontin, and osteonidogen.^20,60 Cell culture studies have shown an up-regulation of various cytokines, biological markers, and interlukines, like IL-1α, IL-1β, lL-4, IL-6, osteocalcin, alkaline phosphatase, bone sialoprotein, osteopontin, BMP-2, PGE2, and cyclooxygenase-2, by MTA.^9,20 Shabahang et al concluded that MTA can induce the formation of apical hard tissue with significantly greater consistency than osteogenic protein-1 and calcium hydroxide.65 The biologic activity of MTA is attributed to the high pH level associated with formation of calcium hydroxide. Current studies indicated that the biological activity of MTA is attributed to the formation of hydroxyapatite-like precipitate on its surface. GMTA was observed to produce twice as much hydroxyapatite crystals as WMTA, suggesting different levels of bioactivity of the two materials.^18,67

Solubility

MTA displays low or nearly no solubility, which is attributable to addition of the bismuth oxide.^5,8 Chemical analysis and x-ray diffraction have demonstrated insolubility of 18.8% in water.5 Although MTA forms a porous matrix characterized by internal capillaries and water channels with increased liquid/powder ratio—which can increase the porosity and the solubility further—the solubility levels of GMTA have been shown to be stable over time.^13,74

Radiopacity

MTA has a mean radiopacity of 7.17 mm of equivalent thickness of aluminum, which is less than that of IRM, super EBA, amalgam, or gutta-percha.^5,75 It has a similar radiodensity to zinc oxide eugenol and slightly greater radiopacity than dentin. Apart from these characteristics, MTA does not react to or interfere with restorative materials like glass-ionomer cements or resin-based composites, which are the commonly used permanent filling materials with MTA.⁷⁶

Conclusion

An ideal endodontic material should adhere to tooth structure, maintain a good seal, be insoluble in tissue fluids, dimensionally stable and nonresorbable, and radiopaque, and exhibit biocompatibility with a certain degree of bioactivity. Among the various available endodontic materials, MTA is currently the biomaterial that posses most of these characteristics. Nevertheless, the extrapolation of results obtained in in-vitro studies should be undertaken with caution when applied to clinical conditions.

Editor's Note: To read Part 2 of this series, click here. 

11. Oliveira MG, Xavier CB, Demarco FF, et al. Comparative chemical study of MTA and Portland cements. Braz Dent J. 2007;18(1):3-7.

About the Authors

Neeraj Malhotra, MDS, PGDHHM
Reader
Department of Conservative Dentistry & Endodontics
KDDC
Mathura, U.P., India

Antara Agarwal, MDS
Senior Dental Consultant
Cosmetic Dentistry & Endodontics
Indus Hygiea, Unit of Indus Speciality Health
Mohali, Punjab, India

Kundabala Mala, MDS
Professor
Department of Conservative Dentistry and Endodontics
Manipal College of Dental Sciences
Mangalore, Karnataka, India