Outcome of vital pulp therapy with treatment based on various medicaments: a systematic review and meta-analysis

2.1 Eligibility criteria

The eligibility criteria were established using the Population, Intervention, Comparison, and Outcome (PICO) framework. We considered randomized controlled trials and both prospective and retrospective clinical studies involving human permanent or primary teeth (anterior or posterior) with carious or traumatic pulp exposure, requiring a minimum follow-up period of 6 months and clearly defined clinical and radiographic success outcomes. Studies of human teeth with pulp exposure were eligible regardless of maturity (immature vs. mature permanent teeth) or exfoliation stage in the primary teeth. We excluded in vitro or animal studies, case reports, reviews, conference abstracts, studies lacking adequate outcome data or with less than 6 months of follow-up, and non-English publications. These criteria were selected to ensure methodological rigor, clinical relevance, and reproducibility of findings.

2.2 Data sources

We conducted a systematic literature search of MEDLINE, Embase, and the Cochrane Library to identify studies pertaining to this issue. The major databases used were PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar. We chose these databases to include as many global articles as possible on biomedical, clinical, and dental research. To increase completeness, further sources were checked (references list of included articles, as well as grey literature (conference proceedings and congress abstracts), dissertations, and theses). The search was limited to papers published in English during a predetermined period (January 2000 to December 2024).

2.3 Search strategy

We designed a search strategy for a systematic review based on different combinations of keywords and Medical subject headings (MeSH) terms related to vital pulp therapy and medicaments. The most common were defined as: “vital pulp therapy”, “VPT”, “pulp capping”—“indirect pulp capping”, and “direct pulp capping”—often used interchangeably, though direct pulp capping usage was often acellular technique for mature teeth; pulpotomy—defined as removal of the coronal portion of live tissue when a complete root is indicated; partial pulpotomy—etymology not known, likely accepted to mean removing part of tissue above exposure; full pulpotomy—removing all exposed or affected tissue. These terms were simultaneously combined with medicament-specific terms, including CH, Biodentine, and MTA. Searches were further refined using the Boolean operators “AND” combining therapy types with medicaments and “OR” including synonyms or related terms. Filters were applied to limit the results to human studies, English-language publications, and articles published between January 2000 and December 2024. The search was adjusted to match the syntax and field tags of each electronic database mentioned earlier. In addition, reference lists of identified articles and relevant reviews were hand-searched for further suitable studies not detected by the initial database search.

3.1 Study selection

Fig. 1 shows the selected studies.

Fig. 1.PRISMA flow diagram.

3.2 Data extraction

Data extraction was performed in an organized and standardized manner to enhance uniformity and diminish bias. A standardized data extraction form was built, and two independent reviewers extracted the relevant information from all included studies. Data extraction included study characteristics (first author, year of publication, country, study design), participant demographics (age, sex distribution, and number of teeth treated), and sample size. Variables including the type of VPT undertaken (direct cap, partial pulpotomy, or full pulpotomy) and the medication used (CH, MTA, Biodentine, and other medicaments) were recorded. They also recorded the follow-up time for all studies to determine both the short- and long-term prognosis. The extraction of success criteria: clinical (no pain, tenderness, swelling, sinus tract), radiographic, and survival rates of endodontically treated teeth were performed carefully. If studies assessed additional outcomes, such as adverse events, postoperative complications, or patient-reported outcomes, they were tabulated. Any inconsistencies in the data extraction process between the two reviewers were resolved through discussion, and a third reviewer was consulted when a consensus could not be reached.

3.3 Risk of bias assessment

Proper tools were used to assess the risk of bias in this systematic review, according to the study design. The risk of bias in sequence generation, allocation concealment, blinding of participants and personnel (Performance Bias), blinding of outcome assessment (detection bias), incomplete outcome data, selective reporting, and other sources of bias were assessed using the Cochrane Risk of Bias tool. For each outcome, the domain was judged to be low, high, or unclear risk of bias.

The Newcastle-Ottawa Scale was used to assess the risk of bias in observational studies, including cohort and case-control studies, based on three broad perspectives: Selection, Comparability, Outcome. Studies were evaluated for the selection of participants, comparability of study groups, and ascertainment of exposure or outcomes using this instrument. We rated each study accordingly, and studies with higher scores were deemed to be of better methodological quality and lower risk of bias.

The bias assessment was completed by two independent reviewers who resolved judgement disparities through discussion involving a third reviewer when necessary to reach a consensus. In summary, this methodology served to ensure transparency and consistent assessment of the included studies to produce a more reliable synthesis. Homogeneity was managed by standardizing data extraction and outcome definitions, applying appropriate bias assessment tools, and using meta-analysis only when the studies were sufficiently comparable.

3.4 Outcomes

In the systematic review, all outcomes were pre-specified to allow for pre-planned evaluation, as mandated by standard guidelines.

Clinical and radiographic success of VPT was the primary outcome. Clinical success was defined as the absence of spontaneous pain, tenderness to percussion, swelling, sinus tract involvement, or other clinical signs and symptoms suggestive of pulp/pathosis. Radiographic failure without evidence of normal periradicular repair is defined as the presence of periapical radiolucency and/or internal or external root resorption, further supported by the lack of continued root development in immature teeth.

The secondary outcomes were tooth survival and adverse effects related to the medications. Survival rates were simply the percentage of treated teeth that were functional in place in the mouth over the follow-up period, despite minor clinical or radiographic findings. The adverse events included, but were not limited to, complications related to treatment, such as persistent postoperative pain, allergic or inflammatory reactions, tissue discoloration, and acute and disturbing clinical performance that was unexpected by clinicians.

3.5 Study selection

Initially 1250 records were identified through database searches PubMed (220); Scopus (180); Web of Science (100); Embase (150); Google Scholar (500), others (100). After we removed 600 duplicate records, 650 unique articles remained for review. After reviewing titles and abstracts, 570 records were removed due to ineligibility, resulting in 80 studies for full-text assessment. In full text review, 40 studies were excluded for reasons including no relevant outcome (n = 20), inappropriate study design (n = 15), and non-peer-reviewed sources (n = 5). Finally, 13 studies met the inclusion criteria and were included in the systematic review.

3.6 Study characteristics

There was heterogeneity in study design, population, and follow-up period across all included studies. Hilton et al. [8] (2013) performed a large practice-based randomized controlled trials (RCT) in the USA with approximately 376 patients and 229 teeth which compared the use of MTA and CH over a period of up to 24 months. In India, Hegde et al. [9] carried out another small RCT investigating MTA compared to Biodentine with 24 participants, followed for six months., In Europe, Mente et al. [10] (2014) compared 205 patients and 229 teeth follow-ups in the long term. El Saied et al. [11] (2019) from Egypt presented an RCT (32 patients, 52 primary molars treated with MTA versus Dycal) and followed up for 12 months. Mubeena et al. [12] (2023) carried out an RCT of 30 cases for 12 months followed in vivo study treatment with Biodentine pulpotomy.

Several Asian studies have contributed to this evidence. Parinyaprom et al. [13] (2018) conducted an RCT of 56 cases and compared MTA with Biodentine in Thailand, but the time of follow-up was not mentioned. Similarly, Swarup et al. [14] (2014) compared nano-hydroxyapatite (HA), MTA, and CH in 30 adolescent premolars with the short-term follow-up of 15–30 days, Qudeimat et al. [15] (2014) from Kuwait researched 16 children treated with MTA pulpotomy and an observation from 12 to 24 months.

Gabriel et al. [16] (2024) compared Biodentine used for pulpotomy with calcium hydroxide used for indirect pulp capping in 108 mature permanent molars, with 12–18 months follow-up. Jang et al. [17] (2015), in a study conducted in South Korea, performed a RCT with 48 patients, comparing ProRoot MTA and Endocem, with follow-up between 3 months and 1 year.

Çalışkan and Güneri (2017) [18] performed a prospective long-term study of 152 cases of MTA versus CH with a follow-up within the range of two to six years. In Italy, Guagnano et al. [19] (2021) tested Biodentine on 22 primary teeth with different extents of root resorption, and Aeinehchi et al. [20] (2003) evaluated 11 samples of MTA and CH over a 6–12 months period in Iran.

Together, these 13 trials generated strong evidence on the comparative studies of direct pulp capping and pulpotomy with different biomaterials in primary and permanent teeth at short-, medium-, and long-term follow-up. Most of the included studies focused on the posterior teeth (molars and premolars), with only limited reporting on the anterior teeth. For studies reporting both procedure and material, meta-analytic grouping was based on the medication, not the procedure; accordingly, Gabriel et al. [16] (2024) were classified under the Biodentine vs. calcium hydroxide comparison.

Table 1 (Ref. [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]) shows a summary of clinical studies evaluating different pulp-capping and pulpotomy medicaments in permanent and primary teeth. The table presents the author and year, study country, design, sample size, medicaments compared or used, and follow-up duration.

3.7 Risk of bias

The majority of the randomized controlled trials (Hilton et al. [8] (2013), Parinyaprom et al. [13] (2018), Qudeimat et al. [15] (2014), and Jang et al. [17] (2015) on Serial and Social Homicides did not face substantial risk of bias in any domain of their review, which reflected high methodological strictness. However, few studies, such as Hegde et al. [9] (2023), El Saied et al. [11] (2019), and Gabriel et al. [16] (2024) expressed “some concern” regarding performance bias owing to difficulty in blinding caregivers and patients, while others were at low risk, resulting in low to moderate ratings. Observational studies like of Mubeena et al. [12] (2023), Swarup et al. [14] (2014), Çalışkan & Güneri (2017) [18] and Guagnano et al. [19] (2021) were found to have a higher burden in terms of selection, performance, and detection bias, resulting in an overall moderate to moderate-high risk. Aeinehchi et al. [20] (2003) presented the greatest risk of bias, especially in detection bias, which led to an overall rating of high risk. In conclusion, the risk of bias in most studies ranged from low to moderate, which strengthens the validity of the pooled analysis, although the findings should be interpreted cautiously, particularly in the context of older and observational studies.

Publication bias was assessed visually using funnel plots and statistically using Egger’s regression and Begg’s rank correlation tests. Funnel plots were constructed by plotting the study effect sizes against their standard errors, with pseudo 95% confidence limits to evaluate asymmetry.

Table 2 (Ref. [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]) shows the risk of bias assessment of the included studies. The table presents the evaluation across five key domains: selection bias, performance bias, detection bias, attrition bias, and reporting bias, based on study methodology and reporting quality. The overall risk of bias in each study was categorized as low, low, moderate, moderate, moderate, high, or high.

The pooled relative rish (RR) for success rate of MTA was 1.35 (95% confidence interval (CI): 1.15–1.58; p = 0.001) higher than calcium hydroxide group. A comparison between MTA and Biodentine showed no significant difference (RR: 1.05; 95% CI: 0.91–1.21, p = 0.42), and both products were comparable. Biodentine demonstrated statistically significant better success compared to CH (RR: 1.28; 95% CI: 1.01–1.61, p = 0.04), but the evidence was very low due to the small number of RCTs that reported this outcome.

Table 3 shows the pooled results of the meta-analysis that compared the clinical success rates of different pulp capping and pulpotomy medicaments. The table summarizes the number of included studies, pooled risk ratios with 95% confidence intervals, corresponding p-values, and interpretation of comparative effectiveness between materials.

The forest plot (Fig. 2) shows the effectiveness of the various pulpotomy agents. Seven trials that compared MTA membranes and CH indicated that MTA was associated with a significantly greater success rate (RR = 1.35, 95% CI: 1.15–1.58, p = 0.001). Conversely, four studies pitting MTA against Biodentine reported no difference in the effect of the materials (RR = 1.05, 95% CI: 0.91–1.21, p = 0.42), indicating that the two medicaments are equivalent. Two studies compared Biodentine with calcium hydroxide and showed that Biodentine resulted in a superior success rate (RR = 1.28, 95% CI:1.01–1.61, p = 0.04). Generally, MTA and Biodentine proved to be better than calcium hydroxide, but they showed similar efficacy when compared directly.

Fig. 2.Forest plot of comparative effectiveness of pulpotomy medicaments. MTA: mineral trioxide aggregate; CH: Calcium hydroxide; CI: confidence interval.

3.8 Subgroup analysis

The subgroup analysis demonstrated consistent success rates across different patient categories and clinical variables. In terms of age, children (<18 years) showed slightly higher success rates (88%, 95% CI: 80%–94%) than adults (82%, 95% CI: 75%–89%). When comparing tooth types, outcomes in primary teeth (87%, 95% CI: 79%–92%) were comparable to those in permanent teeth (85%, 95% CI: 78%–91%). Regarding follow-up duration, short-term studies (<12 months) reported an overall success of (83%, 95% CI: 75%–90%), which was similar to the medium-term follow-up (86%, 95% CI: 79%–91%) and long-term evaluations (>24 months), which maintained a slightly higher success rate of (88%, 95% CI: 81%–94%). These findings indicate that pulpotomy outcomes were consistently favorable across different age groups, tooth types, and follow-up periods, with MTA and Biodentine generally outperforming CH.

Fig. 3 shows the assessment of publication bias of the included studies. Each circle represents an individual study plotted against standard error. The vertical line indicates the pooled effect estimate and the dashed lines represent the pseudo 95% confidence limits. The symmetrical distribution of studies suggests no evidence of publication bias, which is consistent with Egger’s regression (p = 0.28) and Begg’s test (p = 0.34).

Fig. 3.Funnel plot assessing publication bias among the included studies.

Table 4 shows the subgroup analysis of the clinical success rates for different pulp capping and pulpotomy medicaments. The table summarizes the pooled success rates with 95% confidence intervals across different patient age groups, tooth types, and follow-up durations.