Calcium Silicate-Based Cements in Restorative Dentistry: Vital Pulp Therapy Clinical, Radiographic, and Histological Outcomes on Deciduous and Permanent Dentition—A Systematic Review and Meta-Analysis

Vital pulp therapy aims to preserve the vitality of dental pulp exposed due to caries, trauma, or restorative procedures. The aim of the present review was to evaluate the clinical, radiographic, and histological outcomes of different calcium silicate-based cements used in vital pulp therapy for both primary and permanent teeth. The review included 40 randomized controlled trials from a search across PubMed, LILACS, and the Cochrane Collaboration, as well as manual searches and author inquiries according to specific inclusion and exclusion criteria. A critical assessment of studies was conducted, and after data extraction the results were submitted to a quantitative statistical analysis using meta-analysis. The studies, involving 1701 patients and 3168 teeth, compared a total of 18 different calcium silicate-based cements in both dentitions. The qualitative synthesis showed no significant differences in short-term outcomes (up to 6 months) between different calcium silicate-based cements in primary teeth. ProRoot MTA and Biodentine showed similar clinical and radiographic success rates at 6 and 12 months. In permanent teeth, although the global results appeared to be well balanced, ProRoot MTA generally seemed to perform better than other calcium silicate-based cements except for Biodentine, which had comparable or superior results at 6 months. Meta-analyses for selected comparisons showed no significant differences in clinical and radiographic outcomes between ProRoot MTA and Biodentine over follow-up periods. The present review highlights the need for standardized definitions of success and follow-up periods in future studies to better guide clinical decisions. Despite the introduction of new calcium silicate-based cements aiming to address limitations of the original MTA. ProRoot MTA and Biodentine remain the most used and reliable materials for vital pulp therapy, although the results did not deviate that much from the other calcium silicate-based cements. Further long-term studies are required to establish the optimal CSC for each clinical scenario in both dentitions.


Introduction
The primary aim of vital pulp therapy is to preserve the vitality of the dental pulp when it is exposed due to caries excavation, trauma, restorative procedures, or anatomical anomalies.The principles underlying this treatment are based on cellular mechanisms involved in pulp repair and bridge formation, which create an environment that induces hard tissue formation by the remaining pulp cells, seals the exposure site and contributes to sustained pulp vitality [1,2].Bacterial contamination, resulting from pulp tissue exposure, promotes an immune response followed by cell recruitment from the dentin-pulp complex and hard tissue formation by differentiated progenitor cells, leading to reparative dentin formation [3].In clinical practice, pulp capping materials are placed between the vital pulp and the external environment to protect the pulp and the exposure site [1,2].Minor indirect trauma to pulp tissue without exposure stimulates existing primary odontoblasts to produce reactionary dentin.Therefore, materials used in vital pulp treatments should adhere to biological principles, such as adequate biocompatibility and bioactivity, and consequently promote dental pulp stem cell activity and pulp healing in permanent teeth [4].
In short, vital pulp therapy techniques include various definitive options for both primary and permanent teeth.These options, from least to most invasive, are direct pulp capping [5], partial pulpotomy [6,7], and full/coronal pulpotomy.Ultimately, treatment selection depends on the extent of the remaining healthy pulp tissue and the size of the exposure [5,8].
The optimal endodontic material, which can guarantee long-term treatment success, should include the following characteristics: biocompatibility, radiopacity, antibacterial properties, dimensional stability, ease of handling, resistance to blood contamination and dislodging forces, the ability to set in a wet environment, and hard-tissue conductivity [9,10].Additionally, it should block the communication pathways of bacteria and fluids between the root canal system and adjacent dental tissues [11,12] to ensure a biological seal, stimulate hard tissue production, and induce tissue repair [13,14].Many materials have been used (or suggested for use), including adhesives, calcium hydroxide, or calcium silicate-based cements [15].Nowadays, it is commonly accepted that the last group is the gold standard for vital pulp therapy procedures.
Mineral Trioxide Aggregate (MTA, Dentsply, Tulsa, OK, USA) was the first calcium silicate-based cement introduced into the market and has been widely studied for its effects on primary and permanent teeth [15].MTA offers properties such as biocompatibility, antimicrobial effects [5,[16][17][18], and the ability to maintain pulp integrity and physiological function [18,19].Furthermore, it has been found capable of preventing infiltration, exhibiting good sealing ability [5,16,17,20], inducing hard tissue formation [5,21], and promoting tissue neoformation when placed in contact with dental pulp or periradicular tissues, without cytotoxic effects [18,22].However, handling difficulties, long setting time, and tooth discoloration have been identified as its main limitations [17,22].
Considering the vast number of calcium silicate-based cements, specifically MTA-type products, that have been introduced into the market, extensive research has been carried out focusing on the effect of these materials on vital pulp treatment in both dentitions.A search in the PubMed database using the combination of terms ("teeth" AND "pulpotomy" AND "MTA") and ("direct pulp capping" AND "MTA") was able to identify 16 previous systematic reviews [15,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37].Although an extensive synthesis has already been conducted, it is important to note that many of these reviews focus on comparisons with other material families, such as calcium hydroxide in permanent dentition, or formocresol in deciduous dentition, rather than comparing calcium silicate-based cements to each other.Additionally, the basic studies that do compare these materials to each other present very distinct follow-up times or even define success at different levels (clinical, radiographic, or even histological).However, for clinicians, in addition to knowing which material family is better, it is important to know which specific calcium silicate-based cement is most recommended for each vital pulp treatment.
Considering the lack of a general consensus regarding follow-up periods, success outcomes, or their definitions in basic research studies comparing calcium silicate-based cements, and the fact that previous systematic reviews did not take that into account, the present systematic review was designed to determine if a preferred calcium silicate-based cement exists for each type of vital pulp treatment in both dentitions.This consideration takes into account the characteristics of dental tissues and the specifics of each treatment option (such as material thickness, extent of pulp exposure, and diagnosis) as well as the clinical situation (including patient age, cooperation, and isolation conditions).
The null hypothesis to be addressed in the present review was that there are no differences between different calcium silicate-based cements concerning clinical, radiographic, and histological outcomes when used for vital pulp therapy in permanent and deciduous dentitions.

Review Registration and Study Design
The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020196232) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [38].

Search Strategy and Information Sources
Three electronic databases (PubMed, LILACS, and the Cochrane Collaboration) were accessed, and an electronic search was conducted for randomized controlled trials comparing the outcomes of at least two calcium silicate-based cements used in vital pulp therapies.Table 1 summarizes the terms and filters used for each database.A hand search was also performed by reviewing all reference lists from the previously identified studies and by searching in three relevant peer-reviewed scientific journals (Pediatric Dentistry, Journal of Endodontics, and International Endodontic Journal) as well as in previously published systematic reviews on the topic.Additionally, the authors of the identified studies were contacted via email and asked if they were aware of any additional information, including published articles, grey literature, or unpublished material.

Study Selection and Screening Process
The final selection of studies followed a three-stage assessment.Initially, the titles and abstracts of the scientific papers were screened and labeled as 'relevant' or 'irrelevant' according to predefined inclusion and exclusion criteria (Table 2) (stage 1).The studies considered relevant in the initial screening had their full texts analyzed and re-labeled using the same predefined criteria (stage 2).In the final stage, all selected papers underwent a critical appraisal of their scientific merit (stage 3).The review search was conducted between August 2019 and June 2021 and was updated in October 2023 and April 2024, considering all studies published from January 1990 until the update date.No language restrictions were applied.

Critical Appraisal
A critical appraisal of the selected studies was conducted using the Critical Appraisal Skills Programme (CASP) checklist for randomized controlled trials [39].Each scientific paper was evaluated by two reviewers (T.X. and J.M.), who scored each CASP question as "yes," "cannot tell," or "no."The results of both reviewers were compared to determine their agreement percentage, and any discrepancies were discussed until a final consensus was reached.The final score percentage for each paper was calculated based only on the consensual "yes" answers.The studies were categorized as having a "high" risk of bias (RoB) if they scored 49% or lower, "moderate" RoB if they scored between 50% and 69%, or "low" RoB if they scored 70% or higher [40].According to the eligibility criteria (I-CASP) (Table 2), the studies with a high risk of bias were excluded from the review.

Data Items and Statistical Analysis
To conduct a proper qualitative synthesis, data regarding patient demographics, tooth groups, preoperative diagnosis, treatment performed, restorative crown filling materials and their placement timing, and clinical and radiographic success rates at available followup times were retrieved from the pooled studies and combined into review synthesis tables.A quantitative synthesis (meta-analysis) was performed on groups where the comparison between two specific calcium silicate-based cements was available in at least three different studies that presented an equivalent definition of success in the assessed parameters over the same follow-up period.Additionally, histological data, such as bridge formation and degree of inflammation, were also included in the qualitative synthesis.
The data from the pooled randomized controlled trials submitted for quantitative synthesis were processed using OpenMeta [Analyst] v. 10.10 software.The pooled results were presented as risk ratio (RR) forest plots using a random-effects model (DerSimonian-Laird test) with a 95% confidence interval (CI).Tau² (estimate of between-study variance) was used to assess heterogeneity among studies, while the Q-Cochran test with the Der-Simonian and Laird method and the I² statistic were used to determine the statistical heterogeneity of outcomes.An I² value of 50% or higher was considered indicative of significant heterogeneity.Possible sources of heterogeneity were assessed by conducting meta-regression [41,42].Statistical significance was set at p < 0.05.

Selected Studies
The search in electronic databases resulted in 683 references, while the manual search identified an additional 39.The response rate from authors was 40% (16 replies out of 40 contacts), resulting in 44 additional recommended studies.From the 766 references initially identified, after excluding duplicates and those that did not meet the inclusion criteria, 70 articles had their full texts screened.From these, a final pool of 40 randomized controlled trials was included in the present review for qualitative analysis, and five of these were also included in the meta-analysis (Figure 1).Reasons for excluding studies  after full-text analysis can be seen in Table 3. Regarding the quality assessment using the CASP questionnaire, the overall agreement between the two reviewers was considered good (Table 4), and the final average CASP score for the 40 included studies was 87%.
articles had their full texts screened.From these, a final pool of 40 randomized controlled trials was included in the present review for qualitative analysis, and five of these were also included in the meta-analysis (Figure 1).Reasons for excluding studies  after full-text analysis can be seen in Table 3. Regarding the quality assessment using the CASP questionnaire, the overall agreement between the two reviewers was considered good (Table 4), and the final average CASP score for the 40 included studies was 87%.The results were presented by the number of the roots, not by the number of the teeth.

Nosrat et al. (2013) [62] I-5, I-CASP All
Under 50% score at CASP-RCT.The results were presented by the number of the roots, not by the number of the teeth.

Nowicka et al. (2013) [63] I-3 All
The study is not randomized.Disparity between the number of teeth for experimental group (11 teeth) and control group (6 teeth).

Song et al. (2015) [66] E-2 All
Short follow-up study using the same sample of another included study presenting a longer follow-up.

Tzanetakis et al. (2023) [70] I-9 All
Clinical and radiographic follow-up evaluation was performed for a median time of 2 years and did not specify the follow-up periods.

Uesrichai et al. (2019) [71] I-9 All
The studies should specify at least one follow-up period.
* Codes for inclusion factors are listed in Table 2.

Deciduous Teeth
The 22 studies focused on deciduous dentitions performed a total of 18 material comparison combinations (Table 8).The most tested combination was the comparison between ProRoot MTA and Biodentine (six studies), which revealed a very balanced success rate between them at various follow-up periods.ProRoot MTA showed clinical and radiographic outcomes above 96.8% and 86.2%, respectively, at a 2-year period, while Biodentine had outcomes above 89.7% and 82.8% during the same period.Four studies from this comparison could be included in the meta-analysis.The forest plots for the 6-month follow-up showed a clinical and radiographic relative risk of 0.994 (0.952-1.037) and 1.002 (0.966-1.040), respectively, with heterogeneity of τ² (0.00), χ² (0.220; df = 2), I² (0%) and τ² (0.00), χ² (0.209; df = 2), I² (0%), respectively (p > 0.05).For the 2-year follow-up, the clinical and radiographic relative risk was 1.011 (0.966-1.058) and 1.007 (0.931-1.089), with heterogeneity of τ² (0.00), χ² (2.053; df = 2), I² (2.6%) and τ² (0.00), χ² (1.150; df = 2), I² (0%), respectively (p > 0.05) (Figure 2).Two studies compared ProRoot MTA and CEM, with both materials showing success rates around 90% at 20 months and 2 years.Additionally, Angelus MTA and Portland cement were compared in two studies, with both showing a 100% clinical and radiographic success rate at 2 years.Both materials demonstrated dentin-like mineralization and dentin barrier formation at the time of tooth exfoliation, which ranged from 6 to 24 months after the vital pulp treatment (Table 9).A thick layer of dentin bridge formation was also observed when comparing White ProRoot MTA and Grey ProRoot MTA.Fifteen more pulp dressing material combinations were tested, with sample sizes ranging from 15 to 52 teeth per group and follow-ups from 6 months to 2 years (Table 8).Nine of these studies used ProRoot MTA, five tested either Angelus MTA or Biodentine, and one compared NeoMTA with NeoPUTTY.None of the combinations documented significant differences among the tested materials.An additional overview of these studies showed a tendency for slightly lower success percentages in the radiographic evaluation compared to the clinical evaluation.Due to the lack of studies, no more combinations were pooled into the meta-analysis.The clinical success criteria were: absence of symptoms of pain, absence of abscess, fistula or swelling, and absence of pathological mobility.
The radiographic success criteria were: absence of periapical radiolucency or interradicular furcation, absence of internal or external root resorption, and absence of widening of the periodontal ligament.

Çelik et al. (2019) [17]
The absence of spontaneous pain, pathologic mobility, tenderness to percussion, swelling, fistula, and gingival inflammation was considered as a clinical success.
Absence of internal/external root resorption and periapical/furcal radiolucency was considered as a radiographic success.Calcific metamorphosis of the pulp was not considered a failure.

Bani et al. (2017) [16]
The criteria for clinical success were: the absence of tenderness to percussion; swelling; fistulation; spontaneous pain; or pathologic mobility.
The criteria for radiographic success were: the absence of postoperative radiographic pathology, such as external or internal root resorption; furcal or periapical radiolucency; widened periodontal ligament spaces.

Guven et al. (2017) 1 [77]
The pulpotomized tooth was considered to be a clinical success if no swelling, pain, fistula, or pathologic mobility occurred.
Teeth were considered to be a radiographic success if they showed no evidence of internal or external resorption or periradicular radiolucency.Pulp canal obliteration (PCO) was not regarded as a failure.

Rajasekharan et al. (2017) [78]
This scoring system was devised to represent severity of changes but not to label an individual tooth as "success" or "failure":  Symptoms such as pain, swelling, tenderness to pressure, and signs such as presence of sinus tract, swelling and tenderness to percussion were evaluated as the clinical criteria for failure.
Internal and/or external root resorption, interradicular radiolucency, and periapical lesions were assessed as the radiographic criteria for failure.

Malekafzali et al. (2011) [80]
The treatment outcome was classified as a failure when one or more of the following signs were present: swelling/abscess, sinus tract, spontaneous pain, and/or pathological mobility.
The treatment outcome was classified as a failure when one or more of the following signs were present: radiograph evaluation detects signs of furcation radiolucency, periapical bone destruction, internal root resorption, and/or pathological external root resorption.
ProRoot MTA vs. MTA Plus Guven et al. ( 2017) 1 [77] The pulpotomized tooth was considered to be clinical success if no swelling, pain, fistula, or pathologic mobility occurred.
Teeth were considered to be a radiographic success if they showed no evidence of internal or external resorption or periradicular radiolucency.Pulp canal obliteration (PCO) was not regarded as a failure.
ProRoot MTA vs. NeoMTA Plus Alsanouni and Bawazir (2019) [81] At each follow-up appointment, the treatment was considered to have clinical failure if one of the following signs and symptoms was present: spontaneous pain; tenderness to percussion or palpation; soft tissue swelling; sinus tract or fistula; or pathologic tooth mobility.
The treatment was considered to have radiographic failure if one of the following signs were present: widening of the periodontal ligament space; furcal or periapical radiolucency; or pathological external or internal root resorption.

Celik et al. (2013) [20]
The following criteria were used for the determination of clinical success: absence of spontaneous pain and/or sensitivity to palpation/percussion; absence of fistula, swelling, and/or abnormal mobility.
The following criteria were used for the determination of radiographic success: absence of radiolucency at the inter-radicular and/or periapical regions, as determined by conventional periapical radiographs taken at all control appointments; absence of pulp canal obliteration (fully obliterated canals); and absence of internal or external (pathologic) resorption that was not compatible with a normal exfoliation process.
White MTA ProRoot vs. Gray MTA ProRoot Agami et al. ( 2004) [82] Teeth were scored as clinical successes if they had no evidence of: pain symptoms; tenderness to percussion; swelling; fistulation; or pathologic mobility.
Teeth were scored as radiographic successes if they showed no evidence of: radicular radiolucency; internal or external root resorption; periodontal ligament space widening.

Hassanpour et al. (2023) [83]
Presenting either of sinus tract, swelling, periapical lesion, spontaneous pain or long-lasting pain, tenderness to palpation and percussion, internal/external root resorption, or interradicular radiolucency was accounted as the treatment failure.

Erfanparast et al. (2018) [84]
The presence of one of the following signs or symptoms was considered as failure of treatment: pain, swelling, sinus tract, pathologic mobility, tenderness to palpation, sensitivity to percussion.
The presence of one of the following signs or symptoms was considered as failure of treatment: radiographic sign of internal and/or external root resorption, periodontal space widening, inter-radicular radiolucency, periapical lesions, and recurrent caries under the restoration.The pulpotomized tooth was clinical success if no swelling, pain, fistula, or pathologic mobility occurred.
Teeth were a radiographic success if they showed no evidence of internal or external resorption or periradicular radiolucency.Pulp canal obliteration (PCO) was not regarded as a failure.
(2023) [88] At each follow-up, the treatment was considered a clinical failure if one or more of the following signs and symptoms were present: pain; swelling; pathological mobility; sinus tract; and tenderness to percussion.
The treatment was considered a radiographic failure if one or more of the following signs were present: widening of the PDL; internal or ex-ternal root resorption; and furcal and/or periapical radiolucency.The treatment was considered clinically successful in the absence of pain, swelling, fistula, and pain on percussion and bites.
Treatment was considered successful radiologically in the absence of periodontal ligament widening, and internal or external root resorption, in addition to evaluating the presence of radiolucency in the furcation area according to the following scores: Score 0: no radiolucency; score 1: radiolucency between 1⁄4 of furcation to periapical areas; score 2: radiolucency between 1⁄4 and 1⁄2 of furcation to periapical areas; and score 3: radiolucency more than 1⁄2 of furcation to periapical areas.The treated teeth with a score of 1 or 2 were considered successful according to the previous criteria.
* The articles were directly cited; 1 References referring to the same study; 2 References referring to the same study.The treatment was considered to be clinically successful when the tooth remained asymptomatic and vital with a standard response to electrical pulp vitality test.
The treatment was considered to be radiographically successful when a dentin bridge was present over the lesion with the absence of periapical radiolucency and no periodontal ligament space widening, calcification, and internal and external resorption.

Azimi et al. (2014) [102]
Presence or absence of postoperative sensitivity was observed to evaluate the periapical status of the teeth by the main operator.
Periapical radiograph of the teeth was taken to evaluate the periapical status of the teeth by the main operator.

Asgary et al. (2022) [103]
The outcome of clinical success/failure was determined by the subjective symptoms and objective observation of inflammation/infection.Objective signs, e.g., abscess, swelling, sinus tract, redness, pain, and tenderness to percussion.
The outcome of radiographic success was classified using a modification of Strindberg's criteria: teeth with normal contour/width of periodontal ligament (PDL) were deliberated as success, and teeth with periapical radiolucency were reported as failure.

Asgary et al. (2017) [73]
Clinical failure was determined by: subjective reports of symptoms by subject.Objective signs included abscess, swelling, sinus tract infection, redness and tenderness associated with tooth.
The outcome of radiographic success: teeth with normal contour and width of PDL were judged as healed, teeth with a decreased size of the periapical radiolucency were judged as healing.Teeth unchanged, increased in size of the periapical radiolucency, or with the appearance of new periapical radiolucency were judged as failed.Internal/external root resorption and pulp obliteration were also assessed radiographically.
ProRoot MTA vs. OrthoMTA     8).Nine of these studies used ProRoot MTA, five tested either Angelus MTA or Biodentine, and one compared NeoMTA with NeoPUTTY.None of the combinations documented significant differences among the tested materials.An additional overview of these studies showed a tendency for slightly lower success percentages in the radiographic evaluation compared to the clinical evaluation.Due to the lack of studies, no more combinations were pooled into the meta-analysis.

Permanent Teeth
Nineteen material comparison combinations were conducted in the 18 studies addressing the permanent dentition response (Table 10).The most common comparison was between ProRoot MTA and Biodentine (six studies).Two of these studies provided very short outcome periods, 1.5 months and 2 months, both reporting a 100% success rate for both materials in clinical and radiographic assessments.Another study achieved the same outcome at a 1-year follow-up.Both materials were able to induce dentin bridge formation at 6 and 8 weeks, while presenting an equivalent level of pulp inflammation (Table 9).ProRoot MTA and Retro MTA were compared twice, with one clinical and radiographic evaluation showing a success rate of approximately 96% for both materials at a 1-year follow-up period.The longest follow-up period was in a study comparing ProRoot MTA and CEM, which noted a radiographic success rate of 84.7% and 78.1%, respectively, and approximately 98% clinical success for both materials at a 5-year control period.This same study was the only one to report a statistically significant difference among all the performed comparison combinations, with the radiographic outcome of ProRoot MTA (94.9%) being significantly higher than that of CEM (86.1%) at the 2-year follow-up period (p < 0.05) (Table 10).All the other 16 combinations present in single studies showed very well-balanced results in all assessed control periods.All comparisons demonstrated acceptable histological responses regarding bridge formation, although ProRoot MTA appeared to have a superior response compared to TheraCal-LC or Retro MTA (Table 9).Due to the limited number of studies, no pulp dressing material combinations tested on permanent teeth were pooled into the meta-analysis.

8W
Dentinal bridge morphology and continuity-formation of hard tissue beneath the cavity in the form of complete dentinal bridge = 5; formation of discontinuous bridge beneath the cavity (incomplete dentinal bridge) = 4; no signs of dentin formation = 0.
Pulp tissue organization and morphology-normal or almost normal pulp tissue morphology = 3; disorganization of pulp tissue beneath the cavity = 2; disorganization of entire pulp tissue = 4. Dentin bridge at the site of injury was uniform and homogenous with Biodentine, followed by ProRoot MTA.Dentinal bridge morphology and continuity-formation of hard tissue beneath the cavity in the form of complete dentinal bridge = 9; formation of discontinuous bridge beneath the cavity (incomplete dentinal bridge) = 0; no signs of dentin formation (0).
Pulp tissue organization and morphology-normal or almost normal pulp tissue morphology = 3; disorganization of pulp tissue beneath the cavity = 2; disorganization of entire pulp tissue = 4.
Normal pulp organization was seen in 33.33% of the teeth in ProRoot MTA, and in 11.11% of the TheraCal group (p = 0.06).Complete dentinal bridge formation rate was 11% and 56% in TheraCal and ProRoot MTA groups, respectively.

8W
Dentinal bridge morphology and continuity-formation of hard tissue beneath the cavity in the form of complete dentinal bridge = 1; formation of discontinuous bridge beneath the cavity (incomplete dentinal bridge) = 6; no signs of dentin formation = 2. Dentinal bridge thickness-more than 0.25 mm = 5; between 0.1 and 0.25 mm = 2; less than 0.1 mm = 2.
Extension of pulp inflammation-absent = 9.Normal pulp organization was seen in 11.11% of the TheraCal-LC group and in 66.67% of the Biodentine group (p = 0.06).
The Biodentine group showed complete dentinal bridge formation in all teeth, whereas this rate was 11% in the TheraCal-LC group.
Dentinal bridge morphology and continuity-formation of hard tissue beneath the cavity in the form of complete dentinal bridge = 1; formation of discontinuous bridge beneath the cavity (incomplete dentinal bridge) = 6; no signs of dentin formation = 2. Dentinal bridge thickness-none than 0.25 mm = 5; between 0.1 and 0.25 mm = 2; less than 0.1 mm = 2.

n/a
In the Retro MTA group, this study revealed the formation of a discontinuous bridge in most cases under the material within the pulp tissue, with no significant inflammatory reaction in partially or completely disorganized dental pulp.This contrasts with ProRoot MTA, which resulted in complete dentin bridge formation in most of the teeth with no inflammation and normal pulp morphology.

Discussion
The growing number of new patents and published studies on calcium silicate-based cements highlights the importance of this treatment option in vital pulp therapy.However, the optimal choice for each clinical scenario, whether in primary or permanent dentition, remains unclear in the literature.Therefore, this review seeks to offer high-quality evidence on the clinical, radiographic, and histological effectiveness of various calcium silicate-based cements used in vital pulp treatment.Different types of calcium silicate-based cements have been identified for each form of vital pulp therapy, which will be further explored to present their current trends and future outlooks.
In pulpotomy and direct pulp capping performed in primary dentition, there were no significant discrepancies between different calcium silicate-based cements.Specifically, there was no evidence to support different clinical and radiographic outcomes in the short term (up to 6 months) when comparing ProRoot MTA with other cements.Compared with Biodentine, ProRoot MTA showed equivalent performance in one study at six months follow-up [76] and in three studies at twelve months [17,76,77].Although ProRoot MTA tended to present superior results in long-term follow-up, these differences were not statistically significant.The type of restorative treatment and the timing of permanent filling did not seem to influence the success of vital pulp treatment.
In permanent dentition, ProRoot MTA achieved better results in vital pulp treatmentpulpotomy and direct pulp capping-compared to other calcium silicate-based cements, except Biodentine, which had similar or better results at six months follow-up.In other comparisons, ProRoot MTA performed better than Portland, OrthoMTA, and RetroMTA at six-and twelve-months follow-up, and Endocem at twelve months.It showed similar performance to iRoot BP and TheraCal-LC at fifteen months and two months follow-up, respectively.This contrasts with the literature, which indicates that all calcium silicatebased materials, except resin-containing formulations, demonstrate favorable biological and histological responses nearly equivalent to ProRoot MTA [110,111].Similar to primary dentition, there was significant diversity in clinical diagnosis (normal pulp or reversible pulpitis), treatment procedures (pulpotomy or direct pulp capping), restorative materials (composite, amalgam, stainless steel crown, ceramic crown, glass ionomer cement, or 3M TM Cavit TM ), and timing of restoration (immediate or deferred), which did not affect the clinical and radiographic results.
Generally, ProRoot MTA showed superior clinical success rates compared to most calcium silicate-based cements and was similar to Biodentine [5,[96][97][98].The differences were not sufficient to justify a different clinical performance, making it more relevant to consider material properties such as handling, setting time, biocompatibility, and tooth discoloration, as well as potential differences between commercial brands, to decide the best material for each patient (considering age and root tooth development) and specific treatment situation.Handling, setting time, and tooth discoloration are particularly important in direct pulp capping and should be considered when choosing a calcium silicate-based cement.
The present review, although limited by the number and quality of included studies for calcium silicate-based cements other than ProRoot MTA, has important strengths.Unlike previous systematic reviews, it aims to answer a specific and clinically relevant question regarding the choice of calcium silicate-based cements for each clinical situation using practical clinical outcome parameters.Although only histological analysis can evaluate the true condition of dental pulp tissue after vital pulp treatment, the follow-up periods for studies with histological evaluations (only two studies in primary dentition and seven in permanent dentition) were short-term, making it impossible to guarantee the long-term prognosis of calcium silicate-based cements in these treatments.
In daily clinical practice, there is no consistent association between clinical signs/ symptoms (e.g., pulp sensibility testing, clinician's assessment of patient pain history, direct observation of pulp tissue during and after hemostasis) and actual histopathology of diseased pulp [72,97].Consequently, the diagnosis of reversible or irreversible pulpitis is not always clear, and the treatment decision between partial or full pulpotomy and root canal treatment is not always obvious.This study considered pulpotomy for both full and partial procedures.
In the present review, pulpotomy was also a treatment option for permanent dentition with a diagnosis of irreversible pulpitis in the studies [73,95,103].This aligns with the American Association of Endodontists (AAE), which considers vital pulp therapy for symptomatic pulps [112].Carious primary teeth diagnosed with a normal pulp requiring pulp therapy or with reversible pulpitis were treated with vital pulp procedures, as recommended in the American Academy of Pediatric Dentistry (AAPD) guidelines [21] and in agreement with most of the studies in this review.Irreversible pulpitis in primary teeth is usually treated with pulpectomy, which is considered more invasive, time-consuming, requiring more effort from children and experience from the dentist, non-biological, and results in a loss of the repair and regenerative properties characteristic of vital pulp therapy [65,113].Recently, like in permanent dentition, the effectiveness of vital pulpotomy has been proven in the treatment of primary teeth affected by symptoms and signs of irreversible pulpitis.In a recent study, the success rate of Well-Root TM PT Bioceramic putty (Vericom, Republic of Korea) was 100% clinically and radiologically after a one-year follow-up, while the success rate of MTA was 95% [93].
The review level of evidence can be classified as Level 1.a (systematic review of randomized controlled trials) according to Joanna Briggs Institute Levels of Evidence [114].The review strengths are the assessment of randomized control trials only, and the review has a high level of evidence classification.While this systematic review provides valuable insights into the clinical, radiographic, and histological outcomes of calcium silicate-based cements in vital pulp therapy, several potential limitations of the included studies must be acknowledged.First, the risk of bias across studies varied, particularly in terms of randomization processes, blinding, and reporting outcomes, which may influence the reliability of the results.Additionally, there was considerable heterogeneity in the study populations, with differences in patient age, dental condition, and treatment protocols, which could affect the generalizability of the findings.The heterogeneity in interventions, such as the types of calcium silicate-based cements used and the variations in follow-up periods, further complicates direct comparisons across studies.Future research should focus on establishing standardized criteria for follow-up periods and success outcomes to enhance comparability across studies; it should also explore the long-term efficacy of different calcium silicate-based cements in diverse clinical scenarios, and evaluate if vital pulp therapy is also a treatment option for symptomatic pulps in primary teeth, as it is in permanent dentition.

Conclusions
In conclusion, the present comprehensive review evaluated the clinical, radiographic, and histological outcomes of various calcium silicate-based cements used in vital pulp therapy for both deciduous and permanent dentition across 40 randomized controlled trials.The findings revealed no significant short-term differences among different cements in primary teeth, with ProRoot MTA and Biodentine showing comparable success rates.However, ProRoot MTA tended to perform better in long-term outcomes for permanent teeth, except when compared with Biodentine, which demonstrated comparable or superior results at six months.This underscores the importance of selecting materials based on specific clinical scenarios and patient conditions.Despite the availability of numerous calcium silicate-based cements, ProRoot MTA and Biodentine remain the most reliable, highlighting the need for further high-quality, long-term studies to guide clinical decisions and establish optimal use for vital pulp therapy.

Figure 1 .
Figure 1.Flow diagram of the search strategy.Figure 1. Flow diagram of the search strategy.

Figure 1 .
Figure 1.Flow diagram of the search strategy.Figure 1. Flow diagram of the search strategy.

Figure 2 .
Figure 2. Risk ratio forest plots comparing the ProRoot MTA and Biodentine in deciduous dentition.From top to bottom: clinical success (6 months); radiographic success (6 months); clinical success (2 years); radiographic success (2 years).No significant differences were noted between both material outcomes the any of the follow-up periods.

Figure 2 .
Figure 2. Risk ratio forest plots comparing the ProRoot MTA and Biodentine in deciduous dentition.From top to bottom: clinical success (6 months); radiographic success (6 months); clinical success (2 years); radiographic success (2 years).No significant differences were noted between both material outcomes the any of the follow-up periods.
actively initiated the formation of reparative dentin in each tooth.Impossible to quantify from the graphic presented.n/an/a MTA and Biodentine actively initiated the formation of reparative dentin in each tooth (n = 11).The thickness of the dentin bridges displayed no significant different between the MTA and Biodentine groups.and continuity-formation of hard tissue beneath the cavity in the form of complete dentinal bridge = 5; formation of discontinuous bridge beneath the cavity (incomplete dentinal bridge) = 4; no signs of dentin formation = 0.

Table 1 .
Combination of terms used for each electronic database.

Table 3 .
List of the studies excluded from the review.

Table 4 .
Overall agreement scores for the CASP-Randomized Controlled Trial questionnaire.

Table 5 .
Success criteria in deciduous teeth studies regarding the clinical and radiographic parameters.
[86]et al. (2023)C PuttyJoo et al. (2023)[86]The clinical success criteria were (1) the absence of pathologic mobility; (2) the absence of spontaneous pain and/or sensitivity to palpation/percussion; and (3) the absence of gingival swelling or fistula.The radiographic success criteria were (1) the absence of internal/external root resorption; and (2) the absence of periapical/furcal radiolucency or bone resorption.If any clinical or radiological failure occurred, it was considered a failure.

Table 6 .
Success criteria in permanent teeth studies regarding the clinical and radiographic parameters.
* The articles were directly cited;1References referring to the same study;2References referring to the same study.

Table 7 .
Success criteria regarding the histological parameter.

Table 8 .
Outcomes in deciduous teeth studies regarding the clinical and radiographic parameter *.

Table 9 .
Outcomes regarding the histological parameter for both permanent and deciduous dentitions.
n/a: not available.* The articles were directly cited; Permanent t: Permanent teeth; Deciduous t: Deciduous teeth; D, Days; W, Weeks.

Table 10 .
Outcomes in permanent teeth studies regarding the clinical and radiographic parameters.