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Authors: Dr Faizal C P, Dr. Dr Soni Kottayi.

Mineral trioxide aggregate (MTA), has recently been investigated as a potential alternative restorative material to the presently used materials in pediatric endodontics. Several in vitro and in vivo studies have shown that MTA prevents microleakage, is biocompatible, and promotes regeneration of the original tissues when it is placed in contact with the dental pulp or periradicular tissues. This article reviews the various clinical application of MTA in pediatric dentistry.

MTA is a bioactive material that was developed in the early 1990s, originally as a retrograde filling material, and first appeared in the dental scientific literature in 1993 1. Since then, the indications for MTA have expanded significantly. Paediatric dentists have successfully employed MTA in a variety of endodontic applications since the late 1990s. Over the years, further research on the material has resulted in MTA being applied in various clinical situations in addition to its use as a suitable root-end filling material. The diverse application of MTA in the practice of paediatric dentistry is evident in its use as an apical barrier in immature non-vital teeth and in the coronal fragment of fractured roots, as a pulpotomy medicament in primary and permanent teeth, a pulpcapping agent in young permanent teeth, and as a repair material for perforation and resorptive defects2,3.
MTA is a modified preparation of Portland cement .They contain a mixture of a refined Portland cement and bismuth oxide, and are reported to contain trace amounts of SiO2, CaO, MgO, K2SO4, and Na2SO4 . The major component, Portland cement, is a mixture of dicalcium silicate, tricalcium silicate, tricalcium aluminate, gypsum, and tetracalcium aluminoferrite 4,5.Gypsum is an important determinant of setting time, as is tetracalcium aluminoferrate,although to a lesser extent 6. Currently, two different preparations of MTA are available: the original preparation is grey-colored (GMTA); whereas, a white preparation (WMTA) was recently introduced to address esthetic concerns. The d major difference between GMTA and WMTA is in the concentrations of of its contents (Table 1)

Biocompatibility of MTA
A number of in vitro studies have been conducted to evaluate the biocompatibility of MTA ., the results suggest that the cytotoxicity of set MTA is less than that of traditional materials. For example, studies using cultured osteoblastic cells have demonstrated that MTA is less toxic than amalgam, Super EBA, and intermediate restorative material (IRM) 8.However, MTA in its freshly mixed state shows a higher cytotoxicity , which could be due to its high pH 5,6,9
In vitro experiments have also demonstrated that MTA has the capacity to stimulate cell differentiation/activation, which may contribute to hard tissue matrix formation and/or mineralization. Recent studies using pulp cells have also suggested the capacity of MTA to stimulate matrix formation and mineralization during dentinogenesis. Cultured rat pulp cells stimulated with MTA through transwell inserts showed an increased mineralization and upregulation of BMP-2 mRNA and protein . Thus, BMP-2 may be involved in MTA-induced mineralization. The MTA-induced mineralization together with the alkaline phosphatase activity and dentin sialophosphoprotein (DSPP-) and BSP-expressions of cultured pulp cells was further enhanced when enamel matrix derivative (EMD) was added . Thus, a combination of MTA and EMD may promote the differentiation of pulp cells more rapidly than MTA alone10.
Incubation of gingival and periodontal ligament fibroblasts with MTA causes the induction of osteogenic phenotypes such as alkaline phosphatase, osteonectin, osteopontin, and osteonidgen . In a study in which a cementoblast cell line was used, WMTA extracts at lower concentrations induced biomineralization of these cells and caused the upregulation of the mRNA expression of type I collagen and bone sialoprotein 11.
The biocompatibility of MTA has also been studied in vivo as rootend fillings in animals 12,13.These studies reported satisfactory periapical tissue responses and healing with MTA.. MTA has been evaluated in vivo as a pulpotomy medicament in comparison to formocresol and ferric sulphate, and reported to perform ideally as a pulpotomy agent, causing dentine bridge formation and simultaneously maintaining normal pulpal histology.14,15

Table 1 Chemical composition of WMTA and GMTA 7

Chemical WMTA GMTA

CaO 44.23 40.45
SiO2 21.20 17.00
Bi2O3 16.13 15.90
Al2O3 1.92 4.26
MgO 1.35 3.10
SO3 0.53 0.51
Cl 0.43 0.43
FeO 0.40 4.39
P2O5 0.21 0.18
TiO2 0.11 0.06
H2O+CO2 14.49 13.72

Antimicrobial activity of MTA
Various MTA preparations show antibacterial and antifungal activities against different microbial strains16. Similar to calcium hydroxide-based materials, the antimicrobial action of MTA is most likely associated with elevated pH resulting from ionization that releases hydroxyl ions. However, this activity of MTA is limited against some facultative bacteria and has no effect on strict anaerobic bacteria The weaker antimicrobial activity of MTA may be compensated for by its good sealing ability

Clinical applications of MTA
The ability of MTA to induce reparative dentinogenesis or dentin bridge formation has been consistently demonstrated in which direct pulp capping 8-11,17was performed in mechanically exposed pulps . These studies have also shown that MTA causes limited pulp tissue necrosis shortly after its application. Thus, MTA seems less causative compared with calcium hydroxide, which is known to cause the formation of a necrotic layer along the material-pulp interface . Compared with calcium hydroxide, MTA induces reparative dentin formation at a greater rate and a superior structural integrity 18
Also, the majority of studies in which MTA capping was carried out in mechanically pulp-exposed healthy human teeth showed that MTA provides higher frequencies of dentin bridge formation, a better quality (thickness, completeness, and/or integrity) dentin bridge, and milder pulp inflammation compared with calcium hydroxide-based materials 17. In one representative study19 involving 33 healthy third molars [, direct pulp capping was performed with MTA or a hard-setting calcium hydroxide cement (Dycal) in 20 and 13 teeth, respectively, and histological, ultrastructural, and quantitative analyses were carried out after 1 week to 3 months. The MTA-capped pulps were mostly free from inflammation, and hard tissue bridges of steadily increasing length and thickness were formed. Dycal-capped pulps, however, showed the formation of less consistent barriers, which were frequently accompanied by tunnel defects, and pulp inflammation often persisted, even after 3 months
On the other hand, the cellular and molecular events involved in MTA-induced reparative dentinogenesis have been addressed in a limited number of in vivo studies12. In one study, early pulpal cell response after capping with MTA was examined in mechanically exposed dog pulps . MTA initially induced the formation of a zone of crystalline structure and an arrangement of pulp cells with the morphological features of increased biosynthetic activity, for example, nuclear and cytoplasmic polarization and developed cytoplasmic organization. Then, the deposition of fibrodentin, followed by reparative dentin formation, which was characterized by the presence of polarized odontoblast-like cells and a tubular dentin-like matrix, was seen. Thus, the stereotypic pulp defense mechanism by which fibrodentin triggers the expression of the odontoblastic potential of pulp cells may be involved in MTA-induced reparative dentinogenesis10. In another study, the reparative process of mechanically exposed rat molar pulps capped with MTA was investigated by immunohistochemistry 20. The reparative process involved initial deposition of osteopontin in the superficial layer of the pulpal matrix followed by increased cell proliferation and the appearance of nestin-immunoreactive newly differentiated odontoblast-like cells. Thus, the reparative dentinogenesis that occurs following MTA capping is primarily governed by the natural healing process of exposed pulps, which involves the proliferation and migration of progenitors followed by their differentiation into odontoblast-like cells. Osteopontin could play a triggering role in the initiation of this process. The expression of dentin sialoprotein, a noncollagenous protein expressed exclusively by odontoblasts, has been detected in newly differentiated odontoblast-like cells after direct pulp capping of human teeth with MTA . Stronger dentin sialoprotein expression was observed in MTA-capped teeth than in Dycal-capped teeth, suggesting a superior dentinogenic effect of MTA.21
Based on the histologic investigations mentioned above, MTA appears superior to calcium hydroxide-based materials with regard to its capacity to stimulate reparative dentinogenesis, as far as mechanically exposed healthy pulps are concerned. MTA and calcium hydroxide share a mechanism of hard tissue formation that can be regarded as the natural healing process of exposed pulps. Thus, MTA should be regarded as “the current gold standard material”, for in vivo pulp capping experiments aimed at investigating the cellular and molecular mechanisms involved in nonspecific reparative dentinogenesis. Based on the in vitro capacity of MTA to stimulate hard tissue-forming cells, however, the possibility that MTA has specific actions for stimulating dentinogenesis cannot be ruled out.

There are several prospective studies22,23 involving the use of MTA materials as pulpotomy dressings for primary teeth . MTA exhibited clinical success at 6 months with radiographic dentin bridges observed in 50% of the specimens .other studies found similar results with WMTA but radiographic analysis was limited only to the mandibular teeth. Within this limitation, results were that 69% of the pulp canals demonstrated signs of stenosis, 11.5% of the pulp canals exhibited dentin bridges, and one canal exhibited possible early signs of internal resorption adjacent to the MTA dressing. . Percinoto et al24. have compared MTA to calcium hydroxide as a pulpotomy dressing, and reported both materials to be equally effective in primary teeth. MTA has also been compared to formocresol and calcium hydroxide as a pulpotomy dressing in primary molars by Moretti et al25. with satisfactory clinical and radiographic outcomes.
One prospective clinical study26 reported MTA as a pulpotomy medicament in 31 vital, cariously exposed, first molar permanent teeth . At 24months, 79% of the 28 teeth available for evaluation maintained a positive response to vitality testing with the remainder free of clinical or radiographic pathology. Sixty-four percent of the specimens had pulpal radiographic hard tissue bridge formation, while pulpotomy in seven teeth that initially presented with immature apices displayed radiographic signs of continued root development .
The histologic pulpal response comparing MTA to calcium hydroxide as pulpotomy dressings was investigated in premolar teeth extracted for orthodontic purposes, reporting that MTA induced a more homogenous and continuous dentin bridge with less pulpal inflammation than calcium hydroxide at both 4 and 8 weeks after treatment 26,27

Root-end filling in immature permanent teeth.

MTA procedure were cited as reduced treatment time, reduced risk of calcium hydroxide induced changes to dentine, and consequently reduced fracture risk, and the early placement
of a sealing and possibly reinforcing coronal/ intra-radicular restorationTwo prospective, observational studies have investigated. MTA as an apical barrier in non-vital immature permanent incisors
3,10. Simon et al.28 reported a range of follow-up periods from 6 to 36 months for 57 teeth, 14 of which were in patients under the age of 16, in which an apical plug of MTA was placed as a barrier.
This group of workers reported a decrease in the size of the pre-existing peri-apical lesion
in 81% of their cases98. A similar study bySaris et al29. reported similar results in 17 non-vital permanent immature incisors. The one-step placement of an MTA apical barrier was viewed as a promising alternative to traditional, multiple-visit apexification with calcium hydroxide. 3,10,28

Apical seal in the non-vital coronal portion of permanent teeth following root fracture.

Root canal treatment of the coronal fragment with calcium hydroxide followed by filling with guttapercha is the traditional treatment of choice for non-vital root-fractured teeth2,3.
As in the case of open root apices, the use of calcium hydroxide has been promoted to induce hard-tissue barrier formation at the fracture site. The hard tissue barrier is then able to serve as a matrix for the condensation of gutta-percha and sealer. In this situation, MTA has the potential to offer all of the advantages noted for one-step root-end filling. Currently, there have been no human or animal studies reported on the use of MTA as an apical barrier for the coronal fragment of the root-fractured tooth. There are, however, case reports explaining the technique with follow-up of up to 2 years. 30

Recent advances
The handling properties of MTA are recognized to be less than ideal, since the working time is limited to a few minutes, even though this slow-setting material requires approximately three hours for initial setting and the cement mixture is somewhat grainy and sandy. Thus, attempts were made to improve these drawbacks by using additives to accelerate setting. Calcium chloride (2% to 15%) has been widely studied as a setting accelerator: it reduces the setting time ,increases the sealing ability and maintains a high pH . Moreover, the addition of calcium chloride did not affect the formation of dentin bridges following pulpotomies in, and thus may not deteriorate the biologic properties of MTA.10 However, calcium chloride reduces the compressive strength of set MTA5,6. One study recommended an admix of 1% methylcellulose and 2% calcium chloride because it improved the handling properties of MTA without reducing its compressive strength . also reduces the setting time while maintaining biocompatibility in vitro 31.
Attempts have also been made to improve the working and physical properties of MTA by developing new calcium silicate-based materials . Among these, NEC (new endodontic cement) is a novel endodontic material consisting of different calcium compounds (i.e., calcium oxide, calcium phosphate, calcium carbonate, calcium silicate, calcium sulfate, calcium hydroxide, and calcium chloride . NEC is reported to show a shorter setting time , better handling properties, and a similar sealing ability compared with those of MTA. When applied to exposed dog dental pulps, both NEC and MTA show favorable responses characterized by the formation of dentin bridges, while Dycal showed inferior responses accompanied by incomplete dentin bridge formation and pulp inflammation 32,33.

MTA has undergone modification and purification from Portland cement to make it more suitable for clinical use. The clinical outcome of MTA seems quite favorable, although the number of controled prospective studies is still limited Attempts are being conducted to improve the working properties of MTA via the addition of setting accelerators shorter setting time better handling properties, and a similar sealing ability .

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More References are available on request