Dental fillings and restorations are invasive to periodontal tissues [22]. Owing to its affordability and effectiveness, amalgam is still the most popular dental filling material in some low- and middle-income countries (LMICs) [23], and its widespread usage and potency have been well established [26 − 24]. SSCs are presently used for the restoration of primary or newly erupted/young permanent teeth severely affected by caries, hypoplastic lesions, or fractures [27]. Teeth restored with amalgam fillings are more prone to plaque accumulation than other materials, primarily due to the uneven surface of amalgam materials [22]. Furthermore, imperfect alignment, improper margin contours, and subgingival placements of SSCs initiate gingivitis near and around primary teeth [28].
The most popular dental restorations for children include dental amalgam fillings and SSCs [29, 30]. However, all dental restorations (e.g., amalgam fillings and SSCs) could potentially cause inflammation and thus increase inflammatory factors [22]. The inflammatory response of the gingiva can be monitored by evaluating changes in the GCF. The GCF serves as a "defensive layer" in the gingival sulcus and shields the beneath tissues against bacterial invasions and external effects [31]. The GCF is, in turn, a critical sample for evaluating and tracking the inflammation in periodontal tissues. GCF, which contains cytokines, bacterial products, and secondary products, serves as a key marker that illustrates the ecology of the gingival sulcus and periodontal pocket [32]. Cytokines (e.g., interleukins) are frequently found in the GCF and could be potent markers for diagnosing periodontal disease [33–35].
Gingivitis increases gingival blood flow, vascular permeability, and the migration of inflammatory cells from the peripheral blood to the gingival groove fluid. As a result, host cells produce and release cytokines and prostaglandins [36]. Hence, elevated levels of inflammatory mediators such as prostaglandin E2 (PGE2), IL-1, and TNF-α in the GCF might ideally indicate disease activity [37].
In the present study, GCF samples were taken before treatment and seven and 21 days after dental restorations with amalgam fillings and SSCs. In the group receiving SSCs, the level of TNF-α was significantly reduced. Moreover, the level of IL-1β cytokine was significantly increased in both groups after seven days. However, the level of IL-1β cytokine was decreased in the group receiving dental amalgam fillings on day 21 post-treatment.
Dental caries are a source of inflammation due to the production of cryogenic microorganisms and other byproducts, as well as the invasion of tooth enamels. In a recent short-term controlled prospective study, Stefanović et al. estimated the concentrations of pro-inflammatory cytokines (IL-1β and TNF-α) in the GCF of decayed and healthy teeth. Like in our study, they reported a reduction in the levels of the inflammatory factors IL1-β and TNF-α after seven days in patients treated with amalgam fillings. They further reported a significant decrease in IL1-β and TNF-α cytokines levels in both groups after 30 days [38]. In the present study, the concentration of IL1-β in patients receiving amalgam fillings first increased within seven days and then decreased significantly on day 21 post-treatment. This discrepancy in the results of short-term analyses between the two studies could be due to the varying mean age of the participants and the GCF sampling methods. Stanković et al. used paper strips for GCF sampling, while we used absorbent paper points in the present study. Additionally, the mean ages of the participants in the present study and the survey carried out by Stanković et al. were "7.15" and "31 ± 6.15" years, respectively. Such an evident disparity in the mean age of the participants between the two studies describes the different levels of hormones and, thus, the concentration of inflammatory factors in the GCF.
Recent research has further investigated the levels of inflammatory factors in the dentinal fluid (DF). DF is a plasma-derived fluid containing serum proteins and immunoglobulins [39–41]. Geraldeli et al. [42] reported a greater level of TNF-α and a lower level of IL-1β in DF derived from extracted sound molars restored with amalgam fillings than in healthy teeth and teeth with caries. However, in the present study, the levels of TNF-α and IL-1β cytokines were reduced 21 days after restoration with amalgam fillings, compared to those in the pre-treatment and control group with healthy teeth. Due to the absence of clinical or radiological symptoms with restored teeth in the study by Geraldi et al., we cannot attribute such a raised level to the additional progression of the carious lesion or other inflammatory mechanisms. Again, the different research designs adopted by these two studies are the next reason for the discrepancy in the results. Geraldi et al. studied extracted third molar teeth and analyzed the extracted and restored teeth separately, providing no data on the post-treatment periodic examination of carious teeth. The authors additionally investigated the restored teeth after a long period of treatment of decayed teeth, confirming the long-term nature of their study. In contrast, the present study investigated patients only within seven and 21 days after treatment. In addition, the target population in the present study was children (mean age: 7.14 years), which led to different results between the two studies.
Geraldi et al. investigated third molar teeth in adult participants, whereas those investigated in the present study were children with a mean age of 7.14.
Subgingival restorations trigger dental biofilm accumulation, thereby provoking the gingival inflammatory response. Such a response may cause adverse environmental conditions for gingival health compared to untreated dental surfaces [43–45]. In line with this, some studies have assessed the level of inflammatory factors in the GCF when applying various restorative materials. Kumar et al. [46] studied the level of IL1-β in the GCF of teeth restored with ceramic, metal, and zirconia crowns immediately after crown placement and 45 and 90 days after dental restoration. The inflammatory factor level decreased after 90 days in the groups receiving zirconia and ceramic crowns.
In contrast, the inflammatory factor level increased in teeth treated with ceramic crowns. In a similar study, Sakallioğlu et al. [47] assessed the levels of various inflammatory factors (e.g., IL1-β) in teeth restored with composite, amalgam and metal-ceramic crowns. In the present study and the study by Geraldi et al. [42], the level of IL1-β cytokine was decreased in patients receiving dental amalgam fillings compared to that in controls. However, Sakallioğlu et al. reported that the level of IL1-β cytokine is significantly increased in the GCF near restored teeth following dental restoration. The mean ages of the participants in the present study and the study conducted by Sakallioğlu et al. were "6–9" and "35–45" respectively. Such a noticeable discrepancy in the mean age of the participants between the two studies reflects differences in hormone levels and, thus, in the concentrations of inflammatory factors in the GCF. In addition, Sakallioğlu et al. studied only two participants in each group, while 17 participants were included in each group in the present study. Thus, the results reported by Sakallioğlu et al. are slightly suspicious due to the small sample size.
The levels of other inflammatory factors have also been recently investigated. For instance, Kumar et al. [48] investigated MIP1-α and MIP1-β chemokine levels in the GCF of children with dental caries and SSCs. They found that the level of inflammatory factors in the GCF of teeth restored with SSC was lower than that in teeth with dental caries and greater than that in healthy teeth. In the present study, the level of IL1-β cytokine in patients receiving SSCs was significantly greater than that in controls, while there was no significant difference in the other variables. The differences between these two studies rely on investigating various inflammatory factors and employing different sampling methods. Kumar et al. [48] used the obsolete micropipette method for GCF sampling, which led to additional inflammation due to trauma during sampling. In contrast, the GCF samples were taken in the present study using absorbent paper points.
Considering the contradictory results reported in these studies, future research should target patients of various age groups and assess the levels of other inflammatory factors with more detailed research designs.