Different Pulp Dressing Materials for the Pulpotomy of Primary Teeth: A Systematic Review of the Literature

Background: Pulpotomy of primary teeth provides favorable clinical results over time; however, to date, there is still not a consensus on an ideal pulp dressing material. Therefore, the aim of the present systematic review was to compare pulpotomy agents to establish a preferred material to use. Methods: After raising a PICO question, the PRISMA guideline was adopted to carry out an electronic search through the MEDLINE database to identify comparative studies on several pulp dressing agents, published up to October 2019. Results: The search resulted in 4274 records; after exclusion, a total of 41 papers were included in the present review. Mineral trioxide aggregate (MTA), Biodentine and ferric sulphate yielded good clinical results over time and might be safely used in the pulpotomies of primary molars. Among agents, MTA seemed to be the material of choice. On the contrary, calcium hydroxide showed the worst clinical performance. Although clinically successful, formocreosol should be replaced by other materials, due to its potential cytotoxicity and carcinogenicity. Conclusion: MTA seemed to be the gold standard material in the pulpotomy of primary teeth. Promising results were also provided by calcium silicate-based cements. Further randomized clinical trials (RCTs) with adequate sample sizes and long follow-ups are encouraged to support these outcomes.


Introduction
Dental caries is an infective, chronic, degenerative and multifactorial condition that represents the most prevalent chronic disease worldwide, mainly in children [1,2]. Tooth decay would seem to be one of the major public health problems related not only to primary teeth but also to permanent ones, and, despite the preventive strategies mostly adopted in developed countries, 2.4 billion adults and 486 million children are affected by dental decay in the permanent and deciduous dentition, respectively [3].
Early caries management should avoid the progressive destruction of dental hard tissue and subsequent loss of dental vitality [4], inducing critical conditions in which premature tooth extraction is required [5]. This is mostly true for primary teeth (due to anatomical considerations, reduced rate of mineralization and high prevalence of risk factors) that show a rapid progression of tooth decay [2,4,6]. Therefore, vital pulp therapy (VPT) has been proposed to preserve the pulp vitality of

Inclusion Criteria -
Human in vivo studies written in English published in peer-reviewed journals; -Comparative clinical articles reporting on different materials applied in pulpotomy of primary teeth; -Definitive restorations of the primary teeth; -Clinical and/or radiographical follow-up of at least 12 months; -Random allocation of the samples.

Exclusion Criteria
-In vitro studies on human and animals; -Systematic reviews, case series, case studies, retrospective studies; -Follow-up < 12 months; -Clinical studies without random allocation of the samples; -Non-comparative papers, namely reporting on only one material used in pulpotomy procedures; -Papers evaluating other clinical procedures that involved the pulp, such as direct capping, indirect capping, endodontic treatment.
After removing the duplicates, some papers were excluded subsequent to reading of the titles. Two review authors (F.I., G.D.G.) independently screened the selected abstracts to identify relevant studies according to the inclusion/exclusion criteria. In case of disagreement, a Senior Author (M.B.) was consulted and agreement was reached. Then, full reports of the selected studies were retrieved and a data extraction form was completed for each paper in an unblinded standardized manner, to determine whether the article should be included or excluded. Excluded studies and reasons for exclusion were reported.

Data Collection
Data extraction was performed by filling a form in with the following data: authors, title, publication year, aim, group distribution, materials compared, intervention, evaluated outcomes, reported results and conclusions.
After a preliminary evaluation of the selected papers, considerable heterogeneity was found in the study design, adopted procedures, outcome variables and results. Therefore, a descriptive analysis of the data was performed, since quantitative assessment and following meta-analysis could not be conducted.

Assessment of Heterogeneity
The following variables were checked to determine heterogeneity: Expertise of the clinician • Restoration materials • Outcome variables

Quality Assessment
The assessment of methodological study quality was performed by two independent authors (F.I. and G.D.G.) following the recommendations for systematic reviews of interventions of the Cochrane collaboration [17] focusing on the following criteria: random sequence generation and allocation concealment (both accounting for selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), or other possible causes of bias.
Assessment of overall risk of bias was classified as follows: low risk of bias if all criteria were met; unclear risk of bias if one or more criteria were assessed as unclear; or high risk of bias if one or more criteria were not met [2].

Search and Selection
The PubMed-MEDLINE search resulted in 4274 records. After duplicate removal, the titles and abstracts were screened according to the inclusion/exclusion criteria and a total of 75 papers underwent full-text reading. Thirty-four articles were excluded  since they did not meet the inclusion criteria; reasons of exclusion have been reported within Table 1. A total of 41 papers  were included in the present systematic review and processed for quality assessment and data extraction. The search strategy has been reported in Figure 1. Table 1. Excluded studies and reason of exclusion.

Author, Year Reason of Exclusion
Kathal et al. 2017 [18] The studied material did not present clinical evidence among scientific literature. Alsanouni et al. 2019 [19] Authors compared the same pulpotomy dressing material. Pratima et al. 2018 [20] Pulpotomy was performed by diode laser prior to MTA. Kang et al. 2015 [21] Authors compared the same pulpotomy dressing material. Akcay et al. 2014 [22] Sodium hypochlorite was applied prior to MTA and might act as a variable. Fernández et al. 2013 [23] Internal root resorption was not considered as a failure.
Liu et al. 2011 [24] Calcium hydroxide paste was mixed with other agents and the obtained material did not present clinical evidence among scientific literature. Holan et al. 2005 [25] Internal root resorption was not considered as a failure. Nematollahi 2018 [26] Authors performed partial pulpotomy that is poorly reproducible and standardizable. Musale et al. 2016 [27] The studied material did not present clinical evidence among scientific literature. Atasever et al. 2019 [28] Sodium hypochlorite was used during pulpotomy procedure and might act as a variable. Huth et al. 2005 [29] The paper reported on the same sample size of Huth et al. 2012. Nguyen et al. 2017 [30] Pulpotomy was compared with root canal therapy. Saltzman et al. 2005 [31] Pulpotomy procedures were different between the evaluated groups.
Grewal et al. 2016 [32] The success of the materials was evaluated on dentin thickness without reproducibility and standardization. Hugar et al. 2017 [33] Incomplete data reported. Kalra et al. 2017 [34] The studied material did not present clinical evidence among scientific literature. Uloopi et al. 2016 [35] Pulpotomy procedures were different between the evaluated groups. Yildiz et al. 2014 [36] No random allocation of the sample size. Ansari et al. 2018 [37] Absence of rubber dam. Gupta et al. 2015 [38] Pulpotomy procedures were performed by laser or electrosurgery. Cantekin et al. 2014 [39] Authors compared the same pulpotomy dressing material. Trairatvorakul et al. 2012 [40] Authors performed partial pulpotomy that is poorly reproducible and standardizable. Zurn et al. 2008 [41] Pulpotomy was obtained by light-cured calcium hydroxide.
Percinoto et al. 2006 [42] Corticosteroid/antibiotic solution was applied as therapeutic dressing and might act as a variable. Ghoniem et al. 2018 [43] No random allocation of the sample size. Biedm-Perea et al. 2017 [44] Retrospective study and no random allocation of the sample size. Airen et al. 2012 [45] Retrospective study and no random allocation of the sample size. Frenkel et al. 2012 [46] No random allocation of the sample size. Cardoso Silva et al. 2011 [47] No random allocation of the sample size. Ibricevic et al. 2003 [48] Retrospective study. Godhi et al. 2011 [49] No random allocation of the sample size. Hugar et al. 2010 [50] No random allocation of the sample size. Ibricevic et al. 2000 [51] No random allocation of the sample size.

Assessment of Heterogeneity
The data extraction of the included studies yielded a considerable heterogeneity between the papers in terms of pulpotomy procedure, materials management, expertise of the clinician, restoration materials, and outcome variables. To better standardize the study comparison, papers reporting pulpotomy procedures different from the standard method were excluded (e.g., absence of the rubber dam, pulpotomy performed with laser ablation or electrosurgery, hemostasis obtained with several agents that could act as bias on the clinical outcomes).
Godhi et al. 2011 [49] No random allocation of the sample size.
Hugar et al. 2010 [50] No random allocation of the sample size.
Ibricevic et al. 2000 [51] No random allocation of the sample size.  Concerning materials management, the included studies evaluated several materials (e.g., MTA, BD, FS, CH, FC) that were applied with almost with the same procedure according to the manufacturer's instructions; however, it should be considered that they were produced by various companies and might have a slightly different composition. Accordingly, the restoration materials reported by the included studies were different (composite, amalgam, glass ionomer cement, stainless steel crowns), however, in order to avoid bias, papers reporting teeth restored with temporary materials were excluded. Regarding the evaluated outcomes, all of the included studies assessed clinical and radiographical parameters; the success criteria used among the articles were similar but not the same and, therefore, it was only possible to make a descriptive comparison between the papers. Finally, the clinician expertise could not be evaluated in each study and the follow-up range varied between 12 and 42 months. Therefore, due to the lack of unequivocal data presentation, the results of the studies were reported separately.

Quality Assessment
Assessments of the risk of bias and of the methodological study quality have been reported in Table 2. Overall risk of bias of the included studies showed high risk mainly in blinding of participants and personnel (28/41 studies), followed by blinding of outcome assessment (12/41 studies) ( Figure 2). The lack of blind clinicians involved in the treatment as well as evaluation of the outcomes could affect the interpretation of the reported results provided in each study, playing a central role in the variability of study conclusions.
The inter-inter-examiner agreement between the two independent authors that performed the quality assessment of the included studies was 0.95.

Outcomes
Data and results reported by each of the included studies are summarized in Table 3. Absence of internal root resorption or furcation radiolucency.
100% of the available teeth were clinically and radiographically successful during all the follow-ups.
100% of the available teeth were clinically and radiographically successful during all the follow-ups The present data suggested that PC might serve as an effective and less expensive MTA substitute in primary molar pulpotomies.
Farsi et al.

12, 18 and 24 months
Absence of pain; swelling; sinus tract; mobility; or pain on percussion.
Absence of internal root resorption; furcation radiolucency; periapical radiolucency; or widening of the periodontal ligament space.
After 24 months, the FC group showed only one case reported pain. On the other hand, 100% of teeth treated with MTA were considered clinically successful.
At the end of the study, the FC group showed five cases with pulp pathosis (13.2%). MTA showed 100% of radiographical success. -BD group: the cavity was filled with BD and then restored by using a SCC cemented with GIC.

months
Absence of palpation-percussion sensitivity, spontaneous pain, hot-cold sensitivity, presence of fistula-swelling, pathologic mobility.
Absence of internal-external resorption, periapical/interradicular bone destruction, disintegration of the lamina dura, enlargement of the periodontal space, and radiological calcific metamorphosis.
There was no statistically significant difference between clinical success rates over time. In both groups one tooth was extracted due to fistula formation at month 12.
The success rates were 80% and 60% for MTA and BD groups, respectively. There were no statistically significant differences between the groups.
Both MTA and BD could be used as pulpotomy agents, but more long-term studies with larger sample sizes are required.
Guvenet al. 2017 [57] MTA-P*** vs.   Absence of internal root resorption, inter-radicular radiolucency and periapical lesion were absent. Hard tissue barrier formation and stenosis were considered as radiographic successes; tooth discoloration was not considered as a failure.
In both groups, 100% of the available teeth were clinically successful during all the follow-up appointments.
The radiographic success rate for both groups was 100% at 12 months. At the end of the 18-month follow-up period, one tooth from FS group presented a radiographic failure (inter-radicular radiolucency), but it was not statistically different from MTA group. The clinical success rate at 12 months was 100% and 81% for MTA and FC, respectively. The difference was statistically significant.
The radiographic success rates for MTA and FC were 96% and 81%, respectively. There was no statistically significant difference between the two agents.
MTA showed clinical and radiographic success as a dressing material following pulpotomy procedure in primary teeth, and it has a promising potential to become a replacement for FC in primary molars. Absence of radiolucencies at the inter-radicular and/or periapical regions, pulp canal obliteration (fully obliterated canals), internal or external resorption.
Comparisons using the log-rank test showed that the clinical survival probabilities of P-MTA and A-MTA were similar and significantly greater than that of the CH group, respectively.
The 24-month cumulative radiographic survival probabilities of the P-MTA, A-MTA, and CH groups were 0.974, 0.908, and 0.446, respectively.
Most radiographic failures were associated with internal resorption, which was observed in 23 teeth in the CH group, compared to none in the P-MTA and three in the A-MTA groups.
Based on the results of this study, P-MTA and A-MTA showed high clinical and radiographic success rates as pulpotomy agents in primary molars. CH showed considerably less clinical and radiographic success than the MTA cements.  At the 12-month evaluation, 100% of G-MTA teeth were clinically successful, while in the W-MTA group 3/18 showed clinical failure as well as two teeth in FC group.
At the 12-month evaluation, 100% of G-MTA teeth were radiographically successful, while in the W-MTA group 3/18 showed radiographical failure as well as two teeth in FC group.
In conclusion, G-MTA was superior to both W-MTA and FC as a pulp dressing agent for pulpotomized primary molars.  Absence of periodontal ligament space, periapical and furcation pathosis, internal resorption.
100% clinical success rates for both groups.
The BD group had a radiographic success rate of 100% at 12-month follow-up, while the DFC group had a success rate of 98.1% at 12 months.
BD and DFC pulpotomy techniques demonstrated favorable clinical and radiographic results in primary teeth, after a 12-month follow-up without any significant differences. Absence of internal or external root resorption and furcation radiolucency.
All the groups were clinically successful over the follow-up period.
At 18 months follow-up, the radiographic success rate for the DFC group was 100%, 66.7% for CH group, 73.3% for LLLT group, and 75% for LLLT + CH group.
DFC provided the best results over the follow-up period. However, LLLT might be considered as an adjuvant alternative for vital pulp therapy on human primary teeth.
At the 12th month of evaluation a success rate of 95% and 85% was seen in the MTA and FC groups, respectively.
At the 12th month of evaluation a success rate of 95% and 85% was seen in the MTA and FC groups, respectively.
MTA provided highly promising results as pulpotomy agent.  In order to ease the reading of the outcomes, the papers were further presented according to the material that yielded the best result after comparison.

MTA
Almost 65% of the included papers (27/41) demonstrated that MTA provided comparable or even better results over time when compared to other materials used in the pulpotomy procedures of deciduous teeth. Specifically, MTA showed better performance than FC after 12 months of evaluation [67,76,86], with a statistically significant difference reported in two out three of the evaluated studies [67,86]. Moreover, better results of MTA in comparison to FC were observed after 24 months of follow-up [55,70,72,85,90], although the differences did not reach a statistical significance except in one study [55]. The same trend was maintained even after 30 [77] and 42 [78] months of evaluation, respectively. In two additional studies [66,88], it was reported that FC showed slightly worse results than MTA at a 24-month evaluation; however, it performed better than other materials assessed during pulpotomy of primary teeth, such as Pulpotec and Emdogain [88], as well as Portland cement and enamel matrix protein [66]. On the other hand, Jamali et al. [65] reported a superiority of MTA in respect to FC after 24 months of evaluation, even though both groups yielded worse results when compared to 3Mixtatin (a combination of simvastatin and 3Mix antibiotic) (78.9% for FC, 90.5% for 3Mixtatin and 88.1% for MTA). However, the differences between groups were not statistically significant.
When solely compared to BD, MTA showed slightly better performances after 12 [56], 18 [61] and 24 [52] months of assessment, without any statistically significant differences among groups. No differences between MTA and BD were reported by Juneja et al. [59], evaluating pulpotomy procedures on primary teeth performed also with FC. However, the authors observed that there were statistically significant differences between FC and MTA at 12 and 18 months, both clinically and radiographically, and between FC and BD at 12 and 18 months, only clinically [59]. Accordingly, Guven et al. [57] demonstrated no differences between BD and MTA groups (total success rates at 24 months were 82.75% BD, 86.2% MTA-P and 93.1% PR-MTA); however, in the same study, primary teeth treated with FS showed the lowest success rate (75.86%) at a 24-month follow-up, although this was not statistically significant.
The comparison between MTA and FS yielded not significant differences after 18 [64] and 24 [71] months of evaluation; however, Doyle et al. [73] demonstrated a significantly lower survival rate for primary teeth treated with eugenol-free FS than MTA, after a follow-up period of 38 months. It should be noticed that Erdem et al. [71] not only reported the same performance for FS and FC (success rate of 88% for both groups) at a 24-month follow-up, but also demonstrated a statistically significant difference between MTA and a group of samples that underwent pulpotomy without use of any pulp dressing agent (96% vs. 68% after 24 months), suggesting the importance of the traditional pulpotomy procedure for the VTP of primary molars.
CH seemed to be the most ineffective material for pulpotomies of deciduous teeth and demonstrated the worst results when compared with MTA [63] after 12 months, and with MTA and FC (MTA 100%, FC 100%, CH 64%) [74], ProRoot MTA and MTA Angelus [68] and MTA and Portland cement [69] after 24 months of evaluation, respectively. In addition, the differences between CH and all tested materials were significantly different at all follow-up points.
Finally, the comparison of MTA with other pulpotomy agents, such as calcium-enriched mixture cement (CEM) [53] and Portland cement [54], provided the same clinical and radiographical performances of all evaluated materials after a follow-up period of 24 months.

Biodentine
El Meligy et al. [87] clinically and radiographically evaluated 108 primary teeth that underwent pulpotomy performed with BD or FC. After 12 months, the authors reported a 100% clinical success rate in both groups and a radiographic success rate of 100% and 98.1% in the BD and FC groups, respectively, although without any statistically significant difference.
Three out of the 41 included papers reported the same [60] or even slightly better results [58,62] of BD in respect to MTA. Specifically, after a follow-up period of 12 months, 39 pulpotomized primary teeth treated with MTA showed a clinical success rate of 92% (36/39) and a radiographical success rate of 97% (38/39), whereas 39 teeth belonging to the BD group showed a clinical and radiographical success rate of 97% (38/39) and 95% (37/39), respectively [62]. A 24-month follow-up evaluation revealed that the clinical success rate of 62 primary molars that underwent pulpotomy was 96.8% (30/31) for both BD and MTA groups and the radiographic success was 93.6% (29/31) for the BD group and 87.1% (27/31) for the MTA group [58].
Therefore, although BD showed slightly better clinical results after one year [62] and radiographic results after two years of follow-up [58], no statistically significant differences were found among groups.

Ferric Sulphate
A total of three out 41 included papers [80,83,92] demonstrated that FS performed better when compared to FC in the pulpotomy of carious deciduous teeth, however without reporting statistically significant differences. Specifically, after 12 months, a total success rate of 92.7% and 83.8% was reported by Fucks et al. [92] and a clinical success rate of 96.7% and 86.7% was reported by Havale et al. [80] in primary molars that underwent pulpotomy with FS and FC, respectively. The latest study [80] also demonstrated a gradual decrease of radiological success rate over time, showing rates of 56.7% and 63.3% for FS and FC, respectively. Moreover, Ozmen et al. [83] compared three pulpotomy agents, such as FC, FS and Ankaferd blood stopper (ABS), and reported a more favorable clinical success rate for FS (100%) than other evaluated materials (87% for both ABS and FC) after a follow-up of 24 months. Concerning radiographical success, the same authors reported gradually reduced rates that were comparable for FS and ABS (87%) and slightly lower for FC (80%).

Formocresol
According to the International Agency for Cancer Research, one of the main components of FC, namely formaldehyde, has been classified as a human carcinogen [93]; due to this reason, FC was not included as one of the keywords in the search strategy of the present systematic review. However, the same material is still largely used and was reported in more than half of the included studies (23/41). Among them, seven papers [75,79,81,82,84,89,91] reported similar or even better results of FC when compared to other agents used in pulpotomy of primary teeth. Durmus et al. [79] reported a 12-month clinical success rate of 97% and 92.5% of deciduous teeth pulpotomized and treated with FC and FS, respectively, as well as comparable radiographical results (87% FC vs.79% FS), without any statistically significant differences among groups. Moreover, FC and FS provided similar results in pulpotomy procedures after 12 (clinical success: 96% FC and 95.7% FS; radiographic success: 100% both FC and FS) and 18 months (clinical success: 96% FC and 87% FS; radiographic success: 100% FC and 91.3% FS) of evaluation [84]. Markovic et al. [82] compared the 18-month clinical and radiographical success of pulpotomies performed on 104 primary molars randomly divided into three groups and treated with FS, FC and CH. FS and FC showed comparable radiographical and clinical success (89.2% and 90.9%, respectively); on the other hand, the CH group demonstrated lower success than other groups (82.3%), although this was not statistically significant [82]. Accordingly, comparing pulpotomies with FS, FC and CH after 12, 24 and 36 months, CH showed the worst results after 24 and 36 months and, even though the values did not reach statistical significance, the failure rate for the CH group was three times higher than the FC one [81]. On the other hand, primary teeth treated with FC after pulpotomy showed slightly better results than the FS group after 12 months of evaluation (96% FC vs. 86% FS), and vice versa after 24 and 36 months of follow-up (85% FC vs. 86% FS and 72% FC vs. 76% FS, respectively) [81]. Fernandes et al. [89] reported a significantly better radiographical success rate of pulpotomy performed with FC compared to CH after 12 (100% FC vs. 50% CH) and 18 months (100% FC vs. 66.7% CH), demonstrating that CH may not be considered suitable in pulpotomy treatment of primary molars, even in combination with Low Level Laser Therapy [89]. Similar outcomes were also reported by Sonmez et al. [91], who observed 2-year follow-up success rates of 46.1%, 66.6%, 73.3% and 76.9% in 80 primary molars treated with CH, MTA, FS and FC, respectively. Although no statistically significant differences were detected among groups, CH seemed to be less clinically appropriate than other evaluated materials. Finally, Noorollahian [75] reported that, after 24 months of evaluation, primary teeth treated with FC during pulpotomy provided better radiographical results than ones that underwent MTA, although both groups yielded a 100% clinical success at the same follow-up point.

Discussion
VTP aims at preserving pulpal tissue and promoting repair of the mineralized tissue barrier (dentin bridge) [94]. In addition, the success of this technique would avoid pulpectomy and subsequent root canal obturation by several materials, that, on turn, could prevent the radicular resorption of the primary molars and alter the development of the permanent teeth [11].
Since there is a lack of a general consensus regarding an ideal pulp dressing material, the aim of the present systematic review was to establish a preferred agent to be used in the pulpotomy procedure of primary teeth affected by deep caries, after raising a PICO question. The evaluation of the included studies suggested that MTA seemed to be the material of choice after pulpotomies. Although it showed successful clinical performances over time, the majority of the authors agreed on its drawbacks, such as high costs, difficult storage and long setting time [4]. Therefore, in some cases, alternative materials may be used. FC had historically been indicated as a valid option in the pulpotomy procedures of primary molars; however, the evidence-based scientific literature has already demonstrated its potential cytotoxicity and carcinogenicity [93]. Due to this reason, FC was not included in the search strategy of the present systematic review; nevertheless, it is largely used and provides some good clinical results. Thus, to supply a complete overview on the topic, papers that compared several materials with FC were included. Seven studies [75,79,81,82,84,89,91] reported better clinical outcomes of FC than FS. On the other hand, the comparison between FC and MTA [55,66,67,70,72,[76][77][78]85,86,88,90], yielded a better performance of the latter after 12, 24, 30 and 42 months of evaluation. Accordingly, El Meligy et al. [87] observed slightly favorable clinical and radiographical outcomes of primary teeth underwent pulpotomy performed with BD than FC, although no statistically significant.
FS yielded more favorable clinical results when compared to FC in 3/41 studies included in the present review [80,83,92]. Even though it provided comparable or slightly worse outcomes than MTA [64,71,73], when the pulpotomized primary molars are going to be replaced by permanent teeth, FS may be used as a safe alternative [95].
In accordance with the scientific literature [95], the present review confirmed that CH seemed to be the most ineffective material for pulpotomies of deciduous teeth and demonstrated the worst results when compared with all tested materials, reaching statistically significant differences at all follow-up points [52,63,69,74,81,89].
The introduction of calcium-silicate-based cements (such as Biodentine) appears to be promising for VTP. Indeed, calcium-silicate-based cements seem to play a central role in regenerative endodontics, inducing pulp regeneration, healing and dentin formation [96]. The present review confirms the previously reported results [4,15], showing similar outcomes when MTA was compared to BD [52,[56][57][58][59][60][61][62]. MTA and BD may be classified as bioactive endodontic cements, due to their bioactivity feature, despite the differences in their chemical compositions [15]. The encouraging clinical properties as well as biocompatibility of calcium-silicate-based cements indicate that they can be considered as a suitable alternative to MTA for pulpotomies in primary molars. However, these preliminary results should be supported by further studies.

Limitations
The main limitation of the present systematic review was the high heterogeneity of the included studies. Although only randomized clinical comparative studies with at least 12 months of follow-up were evaluated, the lack of univocal standard procedures made difficult a precise comparison of the data. Moreover, the use of several materials composition as well as slightly different outcomes evaluation provided high variability in the interpretation of the results and could let to a misjudgment in the Conclusions. Due to this reason, some "confounding" materials reported by several included studies, such as sodium hypochlorite [84], Er:YAG laser [81], diode laser [79] and low level laser therapy [89], were excluded in the evaluation of pulpotomy dressing agents.
It should be further considered the high variability given by the type of restoration material used, although definitive, its interaction with the pulpotomy agent as well as the inconstant time between the pulpotomy treatment and the physiological exfoliation of the same tooth, that would render very hard to establish the success of pulpotomy procedure over time.
The quality assessment of the included studies showed an overall high risk of bias, mainly in blinding of participants and personnel, followed by blinding of outcome assessment. This aspect highlighted the inadequacies in the published studies, as previously reported by Gopalakrishnan et al. [97]. High quality study design and standardized clinical and radiographical protocols are needed to prospectively assess the performances of pulpotomy medicaments used in deciduous teeth.

Conclusions
Within the limitation of the present systematic review, MTA seemed to be the gold standard material in the pulpotomy of primary teeth. Promising results were also provided by BD. On the contrary, CH should be firmly avoided during pulpotomy procedures. Further RCT studies with adequate sample sizes and long follow-ups are encouraged to confirm these outcomes.