The Effect of Dentine Desensitizing Agents on the Retention of Cemented Fixed Dental Prostheses: A Systematic Review

Background and Objectives: The use of desensitizing agents (DA) after tooth preparation to prevent hypersensitivity is well documented in the literature. A fixed dental prosthesis (FDP) should have good retention to be successful. Inadequate retention may result in microleakage, secondary caries, and, eventually, dislodgement of the FDP. The effect of DAs on the retention of FDPs has been widely studied in the literature, but the results are conflicting. Thus, this study aimed to conduct a systematic review to assess the effect of dentine desensitizing agents, used to prevent post-cementation hypersensitivity, on the retention of cemented FDPs. The null hypothesis framed was that there is no effect of dentine desensitizing agents on the retention of cemented FDPs. The focused PICO question was as follows: “Does the application of dentine desensitizing agents (I) affect the retention (O) of cemented fixed dental prosthesis (P) when compared to non-dentine desensitizing groups (C)”? Materials and Methods: Four electronic databases were systematically searched and, on the basis of the predefined inclusion and exclusion criteria, 23 articles were included in this systematic review. A modified CONSORT scale for in vitro studies was used to assess the quality of the selected studies, as all included studies were in vitro studies. Results: Most of the studies compared the effect of more than one type of DA on retention. The results of the selected studies varied due to differences in the composition of tested dentine DAs and types of luting cements. Conclusions: Within the limitations of this study, it can be concluded that the retention values of FDPs cemented using zinc phosphate cement were reduced with most of the DAs, whereas retention values increased when GIC, resin-modified GIC, and resin cements were used with the majority of DAs. These findings are important, as they can guide dentists in selecting the DA before cementing the crowns with the luting agent of their choice, without compromising the retention of the crowns.


Introduction
A fixed dental prosthesis (FDP) is a common treatment modality for replacing missing teeth and for transforming unhealthy teeth into functional and esthetically pleasing ones [1]. To prepare a tooth for an FDP, the coronal tooth structure is prepared, which involves the removal of 1-2 mm of the tooth structure [1]. This procedure leads to the opening of millions of dentinal tubules [2][3][4]. Preparation also reduces the thickness of the dentine (depending upon the type of preparation and location of preparation), which increases the permeability of the dentine [3][4][5][6][7]. This causes pulpal irritation and post-operative hypersensitivity [7,8].
For an FDP to be successful, it should have good retention. Multiple factors affect the retention of FDP, including adequacy of tooth preparation, impression-making, fit and precision of the retainer, space and type of luting agent [27][28][29][30][31]. Inadequate retention may result in microleakage, secondary caries, and dissolution of luting agent [30][31][32][33]. A dislodged FDP is considered to be a failure from the patient's perspective, and he/she may doubt the reliability of the treatment provided by the dentist.
The effect of DAs on retention of FDPs has been widely studied in the literature, but the results are conflicting. Studies by Johnson et al. [34], Jalandar et al. [18], Chandavarkar et al. [8] and Himashilpa et al. [35] have reported higher retention values when GIC was used with Gluma DA, whereas lower retention values were reported by Swift et al. [36], Yim et al. [37] and Sipahi et al. [38]. Similarly, studies by Chandavarkar et al. [8] and Pilo et al. [39] reported higher retention values when GIC was used with pro-argenine-based DAs, whereas Himashilpa et al. [29] reported lower retention values for the same combination. Retention of FDP was reported to be affected by the combined effect of the type of luting agent and DA.
To the best of our knowledge, this is the first systematic review to assess the effect of DAs on the retention of cemented FDPs. The findings are important, as they can guide dentists in selecting the DA before cementing the FDPs with the luting agent of their choice, without compromising retention. Thus, the objective of this study is to conduct a systematic review to assess the effect of dentine desensitizing agents, used to prevent post-cementation hypersensitivity, on the retention of cemented FDPs. The null hypothesis framed is that there is no effect of dentine desensitizing agents on the retention of cemented FDPs.

Permission and Registration
For the planning of this systematic review, registration in the International Prospective Register of Systematic Reviews (PROSPERO) was applied for (CRD388403). The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to structure this systematic review [40].

Search Criteria
Studies were selected based on the following inclusion and exclusion criteria. All published in vitro and in vivo studies in the English language that compared the effect of dentine desensitizers on the retention of full-and partial-coverage FDPs after cementation were included in this systematic review. Studies that were under trial, unpublished abstracts, commentaries, letters to editors, case reports, or dissertations were excluded. Exclusion criteria also included studies in languages other than English, animal studies, studies comparing the sensitivity or bond strength of luting agents to dentine after the application of dentine desensitizers, and studies evaluating materials under trial.
The focused PICO question was as follows: "Does the application of dentine desensitizing agents (I) affect the retention (O) of cemented fixed dental prosthesis (P) when compared to non-dentine desensitizing groups (C)"? P: Cemented fixed dental prosthesis I: Dentine desensitizer application C: Non-dentine desensitizer application O: Retention of crowns Four electronic databases (MEDLINE/PubMed, Scopus, Cochrane Library, and Web of Science-Core Collection) were systematically searched in October 2022 for relevant titles with respect to the formulated PICO question. Details of the keywords and Boolean operators used in the search strategy are listed in Supplementary Table S1. On the basis of the requirements of each electronic database, slight amendments were made to the search strategy. A reference list of articles was searched manually for further relevant titles.

Screening, Selection of Studies, and Data Extraction
After performing the search on the selected electronic databases, the collected titles and their abstracts were independently examined by two reviewers (MES and MM). Duplicate titles were removed, and the titles and abstracts of the remaining studies were assessed against the preset inclusion and exclusion criteria. Full texts of the selected titles were reviewed and the studies that met the inclusion criteria were collected. Two reviewers (MES and MM) discussed the selected studies, and any disputed studies were discussed with third reviewer (S.J.) to resolve disagreements. The reference list of the selected studies was searched manually to check for any supplementary relevant studies that met the requirements. Relevant data were extracted from the studies that fulfilled the inclusion criteria and were tabulated in a self-designed

Quality Assessment of the Included Studies
A modified CONSORT scale for in vitro studies [50,51] was used to assess the quality of the selected studies. The standards of different sections of the published studies can be assessed using the checklist, which includes 14 items. The items included were as follows: "Item 1: Abstract containing structured summary of study design, methodology, results, and conclusions; Item 2a: Introduction should have scientific background and detailed explanation of rationale; Item 2b: Introduction should have study objectives with a defined hypothesis; Item 3: Methodology should contain approach used in the experiment with sufficient details to enable replication; Item 4: Precisely stated primary and secondary outcomes to enable comparison; Item 5: Details of how sample size was determined; Item 6: Details of how random allocation sequence was generated; Item 7: Method used for random allocation concealment; Item 8: Who implemented randomization? Item 9: If randomization is performed, how was blinding followed? Item 10: Statistical assessment; Item 11: Results outcome and estimation; Item 12: Study limitations; Item 13: Details related to funding; Item 14: Details related to the availability of study protocol, if available" ( Table 2).              Table 2. Quality analyses of the included studies using the modified CONSORT scale. 1  2a  2b  3  4  5  6  7  8  9  10  11  12  13 14 Studies

Identification and Screening
An electronic search in PubMed, Scopus, Cochrane, and Web of Sciences resulted in 1454 hits. Of these, 202 articles were duplicates and, hence, were removed. After screening the titles and abstracts of these articles, 1234 articles were removed. The full texts of the remaining 18 articles were reviewed by two authors and, after discussion, all 18 articles were selected for final inclusion in the study. Five articles were added after manual search of the references of the selected articles. Thus, finally, a total of 23 articles were included that satisfied all the selection criteria and addressed the PICO question (Figure 1).

Characteristics of the Selected Studies
A total of 23 in vitro studies were assessed via a selection process in this systematic review. Out of the 23 total studies, 10 studies were conducted in India, 4 in the USA, 2 in Israel, and 1 each in Georgia, Iran, Saudi Arabia, Syria, Turkey, Germany, and Switzerland. The most recent studies were published in 2022, and the oldest was published in 1996 (Table 1). All 23 studies demonstrated comparative analysis of the test and control groups and assessed the effect of desensitizing agents on the retention of cemented crowns. The sample size in the selected studies ranged from n = 20 [31] to n = 420 [35]. remaining 18 articles were reviewed by two authors and, after discussion, all 18 articles were selected for final inclusion in the study. Five articles were added after manual search of the references of the selected articles. Thus, finally, a total of 23 articles were included that satisfied all the selection criteria and addressed the PICO question ( Figure 1). Figure 1. PRISMA flow-chart demonstrating the article selection strategy, preferred reporting items for systematic reviews and meta-analyses.

Characteristics of the Selected Studies
A total of 23 in vitro studies were assessed via a selection process in this systematic review. Out of the 23 total studies, 10 studies were conducted in India, 4 in the USA, 2 in Israel, and 1 each in Georgia, Iran, Saudi Arabia, Syria, Turkey, Germany, and Switzerland. The most recent studies were published in 2022, and the oldest was published in 1996 (Table 1). All 23 studies demonstrated comparative analysis of the test and control groups and assessed the effect of desensitizing agents on the retention of cemented crowns. The sample size in the selected studies ranged from n = 20 [31] to n = 420 [35].

Findings of Quality Analysis
As all of the studies selected in this systematic review were in vitro studies, the modified CONSORT scale [50,51] for in vitro studies was used to perform quality analysis of the selected studies, on the basis of which 61.7% (213/345) of the entries were positively rated ( Table 2). Entries related to the quality of the abstract (Item 1), the introduction (Item 2a, 2b), the intervention (Item 3), the outcomes (Item 4), the statistical methods used (Item 10) in the methodology section, and the results section (Item 11) were rated positively for all of the selected articles. Thirteen studies reported their limitations (Item 12), eight reported details related to the sources of funding (Item 13), six briefly reported details on the randomization method (Item 6), only two reported of the method used for sample size calculation (Item 5), and one study made the full study protocol accessible (Item 14). One study reported steps taken to conceal the random allocation (Item 7), but none of the studies reported having taken steps necessary to prevent bias, such as who made the random distribution sequence (Item 7) and how blinding was performed (Item 9). Overall, the quality of the selected articles was good, with a moderate risk of bias.

Results of Individual Studies
The results of the selected studies varied due to differences in the composition of the tested dentine DAs and the types of luting cements. After the application of liquid-based DAs, the studies reported an increase in the retention of crowns when cemented with resin cements [19,31,36,37,41,46,49], when cemented with GIC [8,18,20,39,42,43], and when cemented with RMGIC [18,37,45,47,48]. However, the use of DAs with ZPC was reported in almost all of the studies to decrease the retention of cemented crowns [11,18,20,37,39,[41][42][43]. The studies also reported a reduction in retention when GIC or resin cements were used with specific DAs [35,37,41,[46][47][48]. The use of a laser as a DA was reported to reduce the retention of crowns when cemented using GIC [8,38,44]. However, Kumar et al. [44] reported that retention increased when laser was used as a DA and resin cement was used for the cementation of retainers (Table 1).
Multiple reasons for post-cementation hypersensitivity have been postulated in the literature, including the opening of dentinal tubules, the chemical composition and the initial low pH of the luting cements, microleakage and bacterial leakage due to polymerization shrinkage of luting agents, desiccation of the tooth, hydraulic pressure on tubules during luting, higher permeability due to smear layer removal, etc. [47,[53][54][55][56]. To minimize this post-cementation hypersensitivity, DAs are commonly used before cementation. These DAs can be in the form of liquids or lasers [8,12,38,[42][43][44][45][46][47]. They act in multiple ways, which include blocking the opening of dentinal tubules, reducing inflammation, depolarization of the nerves, etc. [11,47]. The protective layer formed by DA can affect the retention of cemented crowns by reducing the micromechanical retention tags [15,16,44].
When evaluating the retention of crowns cemented with ZPC, most studies report a decrease in retention values after the application of DAs. [11,18,20,35,37,39,[41][42][43]. ZPC uses irregularities on the dentine surface to attain mechanical retention. Application of most of the DAs blocked these irregularities, thus making the surface smooth and causing a decrease in retention. Meanwhile, in three studies, the retention values were slightly higher [11,18,34]. All three studies used the GLUMA desensitizer, which has been reported to obliterate the bulk of dentinal tubules and infiltrate into them as plugs [57]. This does not alter the irregularities on the dentine and, thus, does not reduce the retention of cemented crowns [18,57].
With GIC as a luting agent, studies have reported contrasting results for retention values with the application of DAs. The type of DA used affected the retention values to a great extent. The retention values were reported to be higher in all studies that used GC Tooth Mousse [8,18,35,43] and One Step [20,36,42] as a DA before cementation. The mechanism of bonding of GIC is chemico-mechanical. The use of GC Tooth Mousse makes the dentine surface smooth, thus helping to increase retention values, as GIC bonds better on smoother surfaces [18,35]. Higher retention values with the application of One Step DA may be due to the chemical affinity of GIC towards HEMA monomers of resin DAs. Thus, after the interface of GIC and resin has been set, it is reported to be like that of RMGIC [20,36,42]. Four studies reported higher retention values when Gluma DA was used [8,18,34,35], whereas three studies reported lower retention values [36][37][38]. The increase in retention values was proposed to be due to the chemical affinity of GIC towards resin sealers containing glutaraldehyde and HEMA [18], whereas the reduction in retention values was proposed to be due to GLUMA being a non-polymerizing resin-based sealer that fills the irregularities of dentine, thus preventing the formation of chelating bonds with dentine [37]. The use of Colgate Sensitive Pro-Relief was reported in two studies to increase retention values [8,39] and in one study to reduce retention values [35]. Chelation between polyalkenoic chains in GIC and calcium carbonate in Pro-Arging-based DAs was presumed to be a possible cause of higher retention values [39], whereas interference in bonding due to the delicate plugs formed by the DAs was presumed to be the cause of poor retention values [35]. Systemp DA increased the retention values in one study [35] and reduced them in the other [48]. The binding of calcium and fluoride minerals released from GIC with the system protein plugs was proposed to be the cause of higher retention values [35]. All Bond [37,41] and lasers [8,38,44] reduced retention values in all of the studies that used them as DAs. Lasers were reported to cause desiccation of the collagen fibrils, as well as producing micro-explosions on the top surface of the dentinal tubules, leading to smear layer formation. These changes interfere with the chemical bonding of GIC with dentine, thus reducing the retention values [44,58].
Retention values when RMGIC is used as a luting agent after DA application varied in different studies. In general, the use of Systemp DA increased retention values [35,48]. Gluma as DA increased retention values in three studies [18,36,45] and decreased them in two studies [35,37]. The use of Tooth Mousse [18,43] or Colgate Sensitive Pro-Relief [10,35] as DAs had no effect on retention values. The binding of protein plugs formed by Systemp with resin tags was proposed to be the cause of higher retention values when Systemp DA was used with RMGIC [35,48]. The increase in retention values with Gluma was proposed to be due to the chemical affinity of RMGIC towards resin sealers containing HEMA [18,45].
Most of the studies reported higher retention values for crowns cemented using resin cements after the application of different DAs [19,31,34,35,37,41,46,49]. Polymerization between the HEMA complex (at the dentine-DA junction) and resin cement [31,59,60], the rewetting properties of HEMA, the buffering capacity of resins [61], and micro-mechanical bonding between protein plugs formed by DAs and resin tags [35,62] may be possible reasons for increased retention values when RC is used with DAs. The use of Pro-Argenine [10] and lasers [44] as DAs was reported to cause no change in retention values when RC was used. It has been proposed that lasers increase the calcium ions on the surface of the dentine, which may increase chelating reactions and resin cements, partially decalcifying the smear layer (formed after laser treatment), thus forming resin tags [44,63].
Adhesive bonding between calcium ions and monomers in resin cement was shown to possess increased retention values compared to other cements [64,65].
The type of dentine desensitizing agent used in the selected studies influenced the outcome of this systematic review. With time, new generations of DAs have evolved that have better handling and properties. The comprehensive search and selection protocol is a key feature of this systematic review. Limitations of this systematic review include a moderate to high risk of bias in the selected studies, the wide variety of tested materials, and the differences in testing conditions. The current systematic review aimed to discuss the effects of DAs on the retention of crowns. The effect of these DAs on hypersensitivity also needs to be addressed, as this is an important parameter when selecting the best DA for patients before crown cementation to minimize post-operative sensitivity.

Conclusions
The following conclusions can be drawn on the basis of this systematic review: 1.
The type of dentine desensitizing agent and luting agent used affect the retention values of the cemented FDPs.

2.
In general, the retention values of FDPs cemented using zinc phosphate cement are reduced with most of the DAs, whereas retention values increase when GIC, resin-modified GIC, and resin cements are used with the majority of DAs.

3.
Blinding protocols should be followed in future in vitro studies to avoid bias.

4.
Dentists should have knowledge regarding the compatibility of DAs and luting cements in order to provide the best treatment to their patients.

Data Availability Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.