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Mineral trioxide aggregate

Mineral trioxide aggregate () is a biocompatible, bioactive endodontic primarily composed of calcium silicates, designed for repairing dental root structures and promoting periapical tissue healing in endodontic treatments. Introduced in the by Mahmoud Torabinejad and colleagues, was developed as a hydrophilic that sets in the presence of , forming a high-pH seal with antibacterial properties and the ability to stimulate formation. It received FDA approval in 1997 for specific dental applications and has since become a standard material in due to its superior sealing ability and marginal adaptation compared to alternatives like . The composition of MTA, such as the ProRoot formulation, typically includes tricalcium silicate, dicalcium silicate, tricalcium aluminate, bismuth oxide for radiopacity, and dihydrate, derived from modified . Upon mixing with , it undergoes a that results in an initial setting time of 70–74 minutes and a final setting of 210–320 minutes, during which it releases calcium ions to form hydroxyapatite-like crystals in contact with tissue fluids. These properties contribute to its bioactivity, enabling MTA to bond chemically with and support osteogenesis, while maintaining a of around 12.5 for effects. Clinically, MTA is widely applied in procedures such as vital pulp therapy (including direct and ), apexification to create apical barriers in immature teeth, repair of root perforations and resorptions, root-end filling in apical surgery, and . Research from 2009–2019, encompassing 19 studies, demonstrates high success rates, such as 100% at 24 months for in primary teeth and lower failure rates (19.7%) compared to (31.5%) in similar treatments. Despite its advantages, MTA's drawbacks include a relatively long setting time, potential tooth discoloration from bismuth oxide, and higher cost, prompting the development of modified bioactive cements to address these limitations.

Composition and Formulation

Chemical Components

Mineral trioxide aggregate () is primarily derived from , consisting of fine hydrophilic particles that include calcium s as the main active components. The primary constituents are tricalcium silicate (3CaO·SiO₂, approximately 50-75%), which contributes to the material's reactivity and strength development, and dicalcium silicate (2CaO·SiO₂, approximately 5-25%), which hydrates more slowly. Additional key phases include (3CaO·Al₂O₃, 1-18%) and tetracalcium aluminoferrite (4CaO·Al₂O₃·Fe₂O₃, 1-18%), with the latter influencing the material's color in certain formulations. Secondary components enhance specific functionalities, such as (gypsum, 2-25%), which regulates the setting time by controlling hydration kinetics. oxide serves as the primary radiopacifier at 20-45%, enabling radiographic visibility, though it can leach over time and affect long-term properties. Newer MTA formulations incorporate alternatives like zirconium oxide as the radiopacifier to mitigate potential drawbacks of oxide, such as reduced mechanical strength. Trace elements and impurities arise from the Portland cement base, including heavy metals like arsenic, lead, and chromium, with arsenic levels in some MTA products reaching up to 21 ppm in acid-soluble forms—exceeding certain international standards for dental materials but generally considered acceptable for short-term clinical use due to limited leaching in physiological conditions. These contaminants raise biocompatibility concerns, as they may leach into surrounding tissues, potentially contributing to cytotoxicity if exposure is prolonged, though overall MTA biocompatibility remains favorable compared to traditional amalgams. Mercury is typically absent or negligible in MTA. Differences between gray and white MTA primarily stem from variations in iron content; gray MTA includes higher levels of (up to 4%) in the tetracalcium aluminoferrite phase, resulting in darker coloration unsuitable for esthetic areas, while white MTA has reduced iron (less than 0.5%), aluminum, and magnesium oxides, leading to improved without significantly altering the core composition.

Commercial Variations

Mineral trioxide aggregate (MTA) is commercially available in several formulations, primarily as powder-based materials mixed with liquid to form a paste for endodontic applications. The original gray MTA, marketed as ProRoot MTA by , was introduced in 1998 and incorporates bismuth oxide as a radiopacifier to enhance visibility on radiographs. This formulation contains higher levels of iron, aluminum, and magnesium oxides, contributing to its gray color. In 2002, launched ProRoot White MTA (WMTA) to address esthetic concerns, reducing iron content to minimize discoloration while maintaining similar sealing and properties. Both gray and white ProRoot variants share a base composition of , dicalcium silicate, , and oxide, with minor differences in trace elements. Modified formulations have emerged to improve handling and setting times. Biodentine, introduced by Septodont in , is a tricalcium silicate-based material that uses in its liquid component to accelerate setting to approximately 12 minutes, making it suitable for faster clinical procedures. EndoSequence BC RRM, produced by Brasseler USA, is a premixed bioceramic variant available in paste or putty forms, emphasizing moisture-activated setting without requiring manual mixing. Similarly, iRoot BP from Innovative BioCeramix is a ready-to-use bioceramic paste designed for root repair, offering high and radiopacity. Developments around 2015 include from Biomed, featuring nano-modified particles for enhanced handling, washout resistance, and dimensional stability in powder-gel systems. TotalFill BC Sealer by FKG Dentaire, a premixed bioceramic option, utilizes and for moisture-initiated setting, focusing on canal obturation with minimal shrinkage. As of 2025, newer formulations such as by , introduced for improved manipulation and bioactivity, and Harvard MTA Universal, a general-purpose cement, continue to expand options in bioceramic repair materials. Most products are supplied as powders in desiccant-lined containers to maintain sterility and prevent moisture absorption, with typical powder-to-liquid ratios of 3:1 by when mixing is required, using sterile or manufacturer-provided solutions. generally ranges from 2 to 3 years when stored in sealed at , away from humidity and light, ensuring consistent performance. Premixed variants like EndoSequence BC RRM and TotalFill BC Sealer come in syringes for direct application, reducing preparation time while upholding sterility through single-use tips.

Properties

Physical and Mechanical Properties

Mineral trioxide aggregate (MTA) demonstrates favorable handling properties, forming a paste-like consistency upon mixing with at a 3:1 liquid-to-powder ratio, which facilitates placement in dental applications. The setting process is highly moisture-dependent, requiring a humid to initiate ; in dry conditions, setting is delayed or incomplete, potentially compromising . Initial setting time ranges from 15 to 75 minutes, while final setting occurs between 2.75 and 4 hours, as evaluated under ISO 6876 standards, with variations influenced by environmental factors such as and the presence of or saline, which can extend times up to 36 hours. Mechanically, exhibits exceeding 50 after 28 days under wet curing conditions, measured according to ASTM C109, with values typically reaching 65-86 for ProRoot MTA. This strength increases progressively over time, from approximately 40 at 24 hours to 67-70 at 21-28 days, attributed to ongoing and formation. In terms of radiopacity, MTA achieves 6.4-8.5 mm aluminum equivalence, primarily due to the incorporation of bismuth oxide as a radiopacifier, surpassing the ISO 6876 minimum of 3 mm and enabling clear visualization on radiographs. Solubility remains low at less than 1.5% in after 24 hours, per ISO 6876, contributing to excellent dimensional with minimal volumetric change (around 0.3%) and microleakage below 5%.

Chemical Properties

Mineral trioxide aggregate () exhibits significant alkalinity, with an initial of approximately 10 immediately after mixing, which rises to 12.5 within three hours of setting due to the formation and release of from the hydration of its components. This elevated is maintained over extended periods, contributing to its chemical reactivity in dental applications. MTA releases substantial amounts of calcium (Ca²⁺) and (OH⁻) ions during the early stages of setting, with peak release occurring within the first 24 to 72 hours and subsequently decreasing over time as progresses. These ions diffuse into surrounding environments, influencing local chemical conditions. The properties of MTA are primarily attributed to its high , which inhibits bacterial growth through disruption of cellular processes; for instance, it demonstrates pH-dependent inhibition against Enterococcus faecalis, producing zones of inhibition typically ranging from 10 to 15 mm in assays. This effect is most pronounced during the initial setting phase when alkalinity is highest. MTA shows relative stability in acidic environments, such as those with 4.5 to 5.5 often found in inflamed dental tissues, where it maintains structural integrity better than traditional cements like , although prolonged acid exposure can slightly increase its solubility. This resistance supports its use in challenging clinical conditions without rapid degradation.

Biological Properties

Mineral trioxide aggregate (MTA) demonstrates high biocompatibility, exhibiting non-cytotoxic effects on human fibroblasts and osteoblasts when evaluated according to ISO 10993-5 standards for in vitro cytotoxicity testing. Studies have shown that set MTA supports robust cell attachment and proliferation, with human periodontal ligament fibroblasts displaying increased viability and spreading morphology compared to unset material. Similarly, osteoblast-like cells (e.g., MG63 line) cultured on MTA surfaces exhibit enhanced alkaline phosphatase activity and mineralization potential, indicating favorable interactions essential for tissue regeneration. In terms of tissue response, MTA induces a mild initial inflammatory reaction characterized by limited infiltration of polymorphonuclear leukocytes and macrophages, which typically resolves within 7-14 days post-implantation in subcutaneous or bone models. This response is notably less severe and shorter-lived than that elicited by traditional materials such as amalgam or intermediate restorative material (IRM), where persistent moderate inflammation may extend beyond 30 days. Histological evaluations confirm that by 15-30 days, MTA sites show minimal residual inflammation and early fibrous encapsulation or bone apposition. Concerns regarding in MTA stem from its Portland cement base, yet analyses reveal only trace levels of (less than 2 ppm) and lead (less than 20 ppm) in commercial formulations like ProRoot MTA, well below the ISO 9917-1 thresholds of 2 mg/kg for and 100 mg/kg for lead considered safe for dental use. These low concentrations do not exceed toxic limits in clinical settings, as studies indicate negligible release over time, mitigating risks of systemic exposure or local cytotoxicity.00137-8/fulltext) MTA also possesses antibacterial substantivity, attributed to the sustained release of calcium ions and hydroxyl ions that create an alkaline environment, inhibiting bacterial formation for up to 21 days against common endodontic pathogens like . This effect is primarily -dependent, with the material maintaining a high surface (around 12.5) during early setting phases to disrupt microbial adhesion and growth.

Mechanism of Action

Setting and Hydration Process

The setting and process of mineral trioxide aggregate (MTA) is a that occurs when the powder is mixed with , leading to the formation of a hardened, colloidal matrix. This process is analogous to that of , as MTA is primarily composed of calcium silicates, and it requires moisture to initiate and complete the reaction. The begins immediately upon mixing and proceeds through several stages: initial dissolution and formation, setting with heat evolution, and final condensation for strength development. The primary hydration reaction involves the calcium silicate components, particularly tricalcium silicate (C₃S, approximately 52% of the powder) and dicalcium silicate (C₂S, about 23%), which react with water to produce (C-S-H) gel and (Ca(OH)₂). These products constitute the bulk of the set material, with C-S-H forming an amorphous, gel-like structure that binds the particles and Ca(OH)₂ precipitating as crystalline needles. In white ProRoot MTA, aluminate phases are minimal (around 4% calcium dialuminate, C₂A), so initial setting relies more on silicate hydration than ettringite formation. The reaction can be represented as: $2(3\mathrm{CaO \cdot SiO_2}) + 6\mathrm{H_2O} \rightarrow 3\mathrm{Ca(OH)_2} + 3\mathrm{CaO \cdot 2SiO_2 \cdot 3H_2O} for tricalcium silicate, and similarly for dicalcium silicate, though C₂S hydrates more slowly, contributing to long-term strength. Bismuth oxide (approximately 20%), added for radiopacity, remains largely inert during hydration but may incorporate into the C-S-H structure without participating in the reaction. Several factors influence the and setting of . is essential, as the material is hydrophilic and will not set properly in dry conditions; exposure to humid environments or physiologic fluids supports the . Saline or can provide this necessary and has been observed to facilitate setting in clinical scenarios, though excessive may compromise properties like . Optimal occurs at body temperature (37°C), where the is balanced for clinical use, and deviations can alter the setting time. The powder-to-liquid also affects the process, with lower s (more liquid) leading to longer working times but potentially weaker final structure due to increased ; standard s are typically around 3:1 by weight for mixing. The resulting microstructure of set MTA is a porous gel matrix dominated by intertwined C-S-H fibers and embedded Ca(OH)₂ crystals, with unreacted particles dispersed throughout. This structure exhibits porosity of approximately 20-30%, which permits gradual ion diffusion post-setting while maintaining overall cohesion. The porosity arises from water evaporation and incomplete filling of voids during gel formation, contributing to the material's bioactivity without compromising its seal.

Bioactive Interactions

Mineral trioxide aggregate (MTA) exhibits bioactive properties that promote mineralization through the release of calcium ions (Ca²⁺), which interact with phosphate ions in the surrounding environment to trigger the formation of hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂] on its surface. This process begins rapidly, with a superficial layer of apatite crystals forming within hours of setting in a phosphate-containing fluid, enhancing biocompatibility and integration with dental tissues. MTA supports tissue regeneration by stimulating odontoblast differentiation from pulpal cells, leading to the formation of a reparative dentin bridge. In animal and human studies, this bridge typically achieves a thickness of 0.2-0.5 mm within 30-90 days, providing a protective barrier over exposed pulp and promoting hard tissue repair. The material's high biocompatibility facilitates this process without significant inflammation, outperforming traditional calcium hydroxide in inducing consistent dentinogenesis. The sealability of against bacterial ingress is achieved through its slight setting expansion of approximately 0.1% and the development of tag-like structures that penetrate dentinal tubules, creating a interface with . These tags, formed during , interlock with the dentin matrix, contributing to long-term adaptation and microleakage resistance superior to many conventional sealers. MTA also promotes angiogenesis and pulp repair by upregulating key cytokines such as transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2), which enhance cellular and vascularization in the pulp tissue. This release supports the regenerative microenvironment, accelerating and integration with vital tissues.

Clinical Applications

Vital Pulp Therapy

Vital pulp therapy using mineral trioxide aggregate (MTA) aims to preserve the vitality of exposed tissue in , promoting healing and dentin bridge formation to avoid . This approach is particularly indicated for mechanical or traumatic pulp exposures smaller than 1 mm in diameter, where bleeding can be controlled within 5 minutes, indicating reversible without extensive inflammation. In direct pulp capping, MTA is applied directly over the exposed pulp after achieving , typically by rinsing with sterile saline or and applying gentle pressure with a moist pellet. The procedure involves placing a 1-2 mm layer of MTA over the exposure site, followed by a bonded composite to the and prevent microleakage. Clinical success rates for MTA in direct reach 91% at 6 months and 86% at 1 year, significantly outperforming , which achieves only 74% at 6 months and 65% at 1 year, due to MTA's superior and . Partial pulpotomy extends vital therapy to young with traumatic exposures or deep carious lesions, involving removal of 2-3 mm of inflamed coronal while preserving the healthy radicular portion. After with saline , is placed as a 1-2 mm thick medicament over the amputated , covered by a moistened pellet for initial setting, and sealed with a permanent . This technique yields success rates exceeding 90% at 12-24 months, with dentin bridge formation observed in approximately 91% of cases, often detectable radiographically within 3 months. MTA's bioactive properties enhance these outcomes by releasing calcium ions that stimulate odontoblast-like cell differentiation and reparative dentinogenesis, forming a protective bridge over the pulp.

Perforation and Resection Repair

Mineral trioxide aggregate (MTA) is widely used for the orthograde repair of lateral and furcation perforations in root canal treatment, where it is placed directly through the access cavity to seal the defect and promote healing. The procedure begins with accessing the perforation site, followed by thorough irrigation using sodium hypochlorite (NaOCl) and saline to remove debris and inflamed tissue. MTA is then condensed into the perforation using small pluggers or paper points to achieve a hermetic seal, often with a moist cotton pellet placed temporarily to facilitate setting. A coronal seal with a temporary or permanent restorative material is applied afterward, and healing is monitored via periodic radiographic evaluation. Clinical studies report success rates of 92% for furcation perforation repair with MTA, with healing observed in 1-2 years post-treatment. In furcal perforations, MTA facilitates outcomes characterized by bone healing through periodontal ligament (PDL) regeneration, as its biocompatibility promotes PDL fibroblast proliferation and cementogenic activity at the site. Radiographic evidence often shows bone formation adjacent to the repair within 3 months, with continued resolution of defects over time. This regenerative response is attributed to MTA's ability to form a seal that prevents bacterial ingress while supporting tissue repair. For resection repair following apicectomy, MTA serves as a retrograde root-end filling material, placed surgically to seal the apical terminus after root-end resection. The procedure involves resecting the root tip, preparing a 3 mm deep root-end cavity parallel to the canal using ultrasonic tips, and condensing MTA into the preparation to achieve adaptation to dentin walls. MTA in this application significantly reduces microleakage compared to amalgam, with studies showing 0% gross leakage for MTA versus 90% for amalgam after 12 weeks in fluid transport models. This superior sealing stems from MTA's physical properties, including low solubility and high post-hydration. Long-term success in root-end fillings exceeds 90% in clinical evaluations, contributing to periapical healing.

Apexification and Root Treatment

Mineral trioxide aggregate () is widely used in procedures for immature with open apices resulting from or , where it serves as an apical plug to create a reliable barrier for subsequent . The material's allows for favorable tissue acceptance at the , promoting periapical without significant . In these cases, is placed as a 3- to 5-mm-thick plug at the apical terminus of the prepared canal to seal the open and prevent extrusion of obturating materials. This approach has largely replaced traditional multi-visit due to 's ability to set in a moist and provide an immediate . The procedure for MTA apical plug placement begins with thorough canal preparation using irrigation with sodium hypochlorite and EDTA to remove necrotic tissue and debris, followed by drying with paper points. is then mixed to a putty-like consistency and inserted into the apical portion of the using a dedicated , such as the Messing or a reverse-angle endodontic carrier, under radiographic guidance to ensure precise placement at 3-5 mm from the radiographic . After insertion, a moist pellet is placed in the to maintain humidity, and the access is sealed with a temporary ; the material is allowed to set for approximately 24 hours before completing with and a sealer using lateral compaction or warm vertical techniques. This single-visit or two-visit protocol minimizes treatment time and patient discomfort while achieving a dense plug with minimal voids. Clinical outcomes for MTA apexification demonstrate high success rates, with periapical healing observed in 90-100% of cases at 12- to 24-month follow-ups, depending on the presence of preoperative radiolucencies. In teeth without initial lesions, healing rates reach 96%, while those with lesions show 85% success, attributed to MTA's sealing properties and bioactivity that induce apical closure and hard tissue deposition over time. Radiographic evidence of apical barrier formation and resolution of pathosis is typically seen within 12 months, with continued maturation in 86-97% of treated teeth. For the repair of internal and external root resorption defects, MTA is applied directly to the resorptive areas after mechanical and to seal the defects and halt progression. When combined with conventional of the , this approach yields high success rates in , as the material's effects and prevent bacterial ingress and support periodontal regeneration around the root surface. 's ability to bond to and promote cementum-like tissue formation is key to restoring root integrity in these non-surgical interventions. In mature teeth undergoing , can be used as an adjunct root canal sealer to enhance the , particularly in cases with irregular canal or minor apical irregularities. When mixed and applied as a thin layer over , it provides superior adaptation and leakage resistance comparable to traditional sealers like or zinc oxide-eugenol, contributing to long-term success rates exceeding 90%. This application leverages 's dimensional stability and moisture tolerance to ensure a bacteria-tight seal without compromising the process.

Advantages, Limitations, and Comparisons

Benefits and Drawbacks

Mineral trioxide aggregate () exhibits excellent , promoting favorable tissue responses and achieving high clinical success rates in endodontic repairs, such as approximately 96% in cases. Its ability to tolerate moisture during placement enhances sealing in humid oral environments, including the presence of blood or exudate, without compromising efficacy. Furthermore, MTA demonstrates long-term stability, with no significant degradation observed over periods exceeding 5 years in successful clinical outcomes, supporting durable restorations. Despite these advantages, MTA has notable drawbacks that can complicate clinical use. The material requires a long setting time of up to 2.75 hours, potentially delaying subsequent restorative procedures. Handling properties are suboptimal, as the powder-liquid mix can be gritty and difficult to manipulate, often staining instruments due to its radiopacifier content. Additionally, MTA incurs a relatively high cost, typically ranging from $30 to $50 per gram depending on the formulation, which may limit accessibility in some practices. Gray MTA variants carry a notable of discoloration, attributed to oxide leaching and oxidation over time. MTA is contraindicated in patients with known allergies to its components, such as bismuth oxide or calcium silicates, to prevent adverse reactions like irritation or hypersensitivity. Placement challenges due to its handling characteristics also make it unsuitable for inaccessible areas where precise delivery is difficult.

Comparisons with Other Materials

Mineral trioxide aggregate () demonstrates superior performance compared to in direct , particularly in inducing bridge formation that is faster and thicker, while eliciting less pulpal . also exhibits significantly lower microleakage rates compared to , contributing to better long-term seal integrity. However, 's higher cost remains a notable drawback relative to the more economical . In comparison to Biodentine, another tricalcium silicate-based material, MTA shares similar levels of bioactivity and , promoting comparable deposition. Biodentine offers advantages in clinical handling with a much shorter setting time of about 12 minutes compared to MTA's 150-165 minutes, allowing for quicker procedures. Conversely, Biodentine shows reduced radiopacity relative to MTA, measuring around 3.5 mm equivalent aluminum thickness versus MTA's 7.17 mm, which may affect radiographic visibility. When evaluated against other bioceramics, such as EndoSequence BC Sealer, generally outperforms in vital pulp therapy applications, achieving success rates of approximately 91% compared to 80-83% for bioceramic alternatives like Biodentine or putty formulations. Bioceramics, however, provide easier handling due to their premixed or paste-like consistency, reducing preparation time and moisture sensitivity during placement. Post-2020 studies, including a 2022 network meta-analysis, indicate MTA's edge in long-term sealing ability, with higher odds of success at 12 months compared to various alternatives in surgical . This reinforces MTA's preference in scenarios requiring durable apical barriers or repairs.

History and Developments

Invention and Early Research

(MTA) was developed in the early 1990s at by Mahmoud Torabinejad and colleagues as a biocompatible dental repair material inspired by the properties of . The material was first described in the in , with an initial study demonstrating its superior sealing ability compared to amalgam and other root-end filling materials , using dye penetration tests under . This seminal publication highlighted MTA's potential for repairing root s and serving as a root-end filling, marking the beginning of its evaluation as an alternative to existing endodontic materials that often exhibited poor and sealing. A for MTA was granted in 1995 to Torabinejad and David J. White, specifying its composition primarily of calcium silicates, bismuth oxide as a radiopacifier, and other mineral oxides derived from . Early animal research in 1995 further validated MTA's biocompatibility through a dog model involving periradicular lesions created via vital pulp extirpation and microbial . In this study, was compared to amalgam as a root-end filling after ; histological evaluation at 30 and 60 days post- revealed significantly less periradicular inflammation and more consistent deposition adjacent to , with no adverse tissue responses observed. The results indicated MTA's superior sealing properties, as evidenced by reduced bacterial penetration and enhanced tissue healing compared to amalgam, establishing its promise for clinical translation in endodontic . The U.S. (FDA) approved MTA in 1997 specifically as a root-end filling material for endodontic procedures, following promising preclinical data. Following FDA approval, ProRoot MTA was commercially launched in 1998 by Dentsply Tulsa Dental. Initial clinical trials from the mid-to-late 1990s demonstrated high success rates; for instance, a prospective study of 27 patients undergoing with MTA as the root-end filling reported a 92% healing rate at 12-month follow-up, assessed radiographically and clinically, outperforming intermediate restorative material (IRM) in promoting periapical repair. Overall, early human trials between 1995 and 2000 consistently showed 80-90% success in outcomes, with MTA facilitating bone regeneration and minimal leakage. A key milestone in MTA's early development occurred in 2002 with the introduction of white MTA (WMTA), formulated to mitigate the tooth discoloration associated with the original gray variant caused by iron oxides in the Portland cement base. This modification retained the core bioactive properties while improving aesthetics for visible restorations, as confirmed by comparative studies showing equivalent sealing and biocompatibility to gray MTA but reduced staining potential.

Recent Advances and Modifications

In the 2020s, advancements in have led to the development of nano-modified mineral trioxide aggregate (Nano-MTA), featuring particle sizes reduced to less than 100 nm to enhance reactivity and performance. These formulations, such as those incorporating nano-silica, demonstrate significantly faster setting times, often around 45 minutes compared to the hours required by conventional , due to increased surface area facilitating quicker . Additionally, Nano-MTA exhibits improved mechanical properties, with compressive strengths reaching up to 70 , supporting its use in load-bearing applications while maintaining . To address MTA's limited inherent antibacterial properties, researchers in 2022 explored enhancements through the incorporation of silver nanoparticles (AgNPs), which extend antimicrobial activity against common oral pathogens like for up to 90 days post-placement. These modifications leverage the of AgNPs to disrupt bacterial cell walls without compromising MTA's sealing ability or bioactivity, as demonstrated in studies evaluating zone of inhibition and reduction. Such integrations have shown sustained efficacy in preventing microbial ingress at root-end fillings and pulp exposures. Post-2020 clinical evidence has further solidified MTA's role in vital pulp therapies. A 2021 systematic review highlighted MTA's superiority in direct , with an of 1.41 for complete hard tissue bridge formation compared to , based on radiographic dentin bridge formation and absence of pulpal across randomized trials. Complementing this, a 2025 BMC Oral Health study compared MTA Angelus to experimental cements like AGM MTA, showing no cytotoxic effects for diluted extracts of MTA Angelus in assays with human dental stem cells (hDPSCs) after 24-72h exposure, though undiluted extracts were cytotoxic after 72h, underscoring its favorable biological response compared to AGM MTA. Looking ahead, research is exploring biodegradable variants of , incorporating polymers like to enable controlled degradation and integration over time, potentially reducing long-term material persistence in regenerative procedures. Similarly, 3D-printable composites are under investigation for fabricating custom plugs and scaffolds, offering precise adaptation to irregular defects and enhanced osteogenesis in endodontic applications. These innovations aim to overcome handling challenges and expand 's utility in personalized .

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