## 4 Discussion  
Mineral Trioxide Aggregate (MTA) was recommended in the past as a repair material for root perforations. It was developed by Loma Linda University (in 1993) and was originally introduced as a retrograde filling material [2]. It was shown to result in a much lower percolation in contact with the surrounding tissues in comparison with the most commonly used materials such as amalgam, intermediate restorative material (IRM), and Super-EBA. For this reason, MTA was considered the material of choice for the repair of root perforation [3] since it was shown to be biocompatible with the periradicular tissue (minimal inflammatory response, ability to allow regeneration of hard tissue structures such as bone and cement) [4], thus facilitating the regeneration of the periodontal supporting apparatus [5,6]. In research on human osteoblast models, it was found that MTA stimulated the production of cytokines, such as interleukin-1\(\alpha\), interleukin-1\(\beta\), and interleukin-6, which are involved in bone turnover [10]. Figure 11: Group A. Scar tissue and rare inflammatory cells at the implant site with MTA after 30 days. Rare inflammatory cells. Col. [PERSON], \(\times\)400. Figure 12: Group B. Dense subcutaneous tissue over the implant with MTA after 30 days. Rare inflammatory cells. Col. [PERSON], \(\times\)400. Sealapex is a calcium hydroxide-based sealer commonly used in endodontics, with both its biostimulating properties and cytotoxicity in contact with the periradicular tissues being extensively discussed in the literature [10; 11; 12]. In general, Sealapex demonstrated reduced inflammatory reaction as compared to other endodontic sealers, showing moderate inflammation at 48 h that became mild in later periods. Other zinc oxide-eugenol-based sealers (Endoflas, Tubliseal) were toxic after 48 h and 7 days. The toxicity decreased gradually in later periods [13]. The cytotoxicity of BioAggregate (BA), the third material used in the study, was also evaluated, as compared to that of MTA, on mesenchymal cell cultures, with the results showing that there was no statistically significant difference between MTA and BA in any of the experimental time periods. DiaRoot BioAggregate displayed in vitro compatibility similar to MTA [14]. In the present study, 7 days after implantation, the presence of more pronounced inflammatory reactions and the presence of multinucleated giant cells were histologically noted in contact with the remaining enclaves of Sealapex and MTA, while in the BA samples, the inflammatory reaction was considerably reduced, as demonstrated by the absence of these cells and reduced inflammatory cell infiltrate. This indicates a biocompatibility of BA with the living subcutaneous tissue, compared to the first two materials. The inflammation [12] and the presence of thicker bands of necrotic tissue in contact with the implanted materials (thicker in MTA compared to Sealapex and BA) after the first 7 days may be accounted for by both the different chemical composition of the cements and the high alkaline pH of MTA: after manipulation, the pH of MTA was 10.2 initially and rose to 12.5, 3 h after mixing, remaining constant thereafter. The maximum pH of Sealapex is 9.1 and that of BA is 12 after setting [15]. At 30 days after implantation, histological analysis [14] of the samples showed no significant differences between the three studied materials [15], with several isolated groups of inflammation cells [16] being found only in one Sealapex sample and one MTA sample. The fact that no inflammation reaction was histologically detected 3 months after subcutaneous implantation with any of the used materials [17] is due to the phagocytic cell activity and tissue repair capacity [18] characteristic to these animals.