Although the use of CH paste as a temporary intracanal medication is mostly employed in replanted teeth, the importance of periodic dressing changes to maintain its action has been highlighted [24]. Therefore, clinicians are seeking a material with advantageous characteristics similar to those of CH that can be used as a single-visit filling material. Mineral trioxide aggregate (MTA) has been considered for this purpose because it has similar properties to those of CH [2526], as well as favorable physical characteristics [27]. It is believed that medications with an alkaline pH that continuously release CH are effective in controlling IRR [28].

Our search yielded 5 animal studies comparing CH with MTA using replanted teeth (Table 1). First, in 2007, Panzarini et al. [29] compared CH with MTA in monkey teeth that underwent immediate replantation. In the extra-alveolar period, the teeth were kept in saline solution. After 7 days, the teeth underwent root canal debridement and the root canals were irrigated with a saturated solution of CH with the aim of making the dentin alkaline [30]. Since there was no significant difference between the study groups regarding IRR and ankylosis, it was concluded that both MTA and CH are suitable root canal filling materials for immediately replanted teeth. Vogt et al. [31] also evaluated the effect of these 2 materials on replanted teeth exposed to a dry environment for 30 minutes. They analyzed the groups at 10 and 60 days. MTA-treated teeth displayed IRR and ankylosis similar to those observed in CH-treated teeth at both 10 and 60 days. However, the CH-treated group showed significantly lower inflammation scores than the negative control group at 10 days.

Three animal studies were performed to assess delayed replantation (with a dry time of 60 minutes). In 2014, Panzarini et al. [32] compared CH with MTA in cases of delayed replantation. In general, they did not find inflammatory cells in the periodontium of the teeth when either CH or MTA was used (except for one specimen in the apical foramen in the CH-treated group). However, in the MTA group, the incidence of ankylosis was significantly lower than in the CH group. In contrast, Marão et al. [33] did not find any significant difference in terms of ankylosis between the 2 groups.

Esteves et al. [34] compared a CH-treated group with a group in which the root canal apices were sealed with an MTA plug and then filled with CH paste. Periapical healing was significantly higher in the MTA-treated group, and although the incidence of ankylosis was not significantly different between the groups, the MTA-treated group was significantly less affected by IRR. The latter effect might be attributed to the fact that the MTA plug blocks the leakage and dissolution of CH paste in the root apex, consequently keeping the CH in the root canal. This enables continuous disinfection of the dentinal walls without contact with periapical tissue fluids [34].

In summary, when CH or MTA was used in cases of immediate replantation of avulsed teeth with long-term placement of intracanal materials (180 days), there was no significant difference in the occurrence of IRR and ankylosis [29]. However, in cases of delayed replantation, the occurrence of IRR or ankylosis in the MTA-treated groups was similar to or lower than that of the CH-treated groups (Table 1) [323334].

Two animal studies compared CH with MTA Fillapex in terms of the occurrence of ankylosis in replanted teeth [3135]. They did not find any significant differences between the 2 groups. However, in one of the studies, when compared to the MTA-treated group, the extent of ankylosis was significantly superior in the MTA Fillapex-treated group at a 60-day follow-up [31]. Negri et al. [17] also compared Sealapex and Endofill with CH and found no significant difference in the occurrence of ankylosis in teeth that underwent delayed replantation. In general, filling the root canals with the aforementioned MTA-based sealers did not provide better results.

Ledermix is a commercial water-soluble paste containing 1% triamcinolone, a corticosteroid, and 3% demeclocycline, a tetracycline. It seems that the corticosteroid in this substance plays an active role in reducing IRR [18]. The only randomized controlled trial found in our search was a study by Day et al., [36] who conducted a multicenter study (at 5 specialist pediatric dentistry centers). They utilized a standardized protocol, including calibration across centers, and did not find any significant difference in periodontal healing and ankylosis between the CH and Ledermix-treated groups. In 2001, Thong et al. [37] conducted an animal study and did not find any differences in IRR between the CH and Ledermix-treated groups when the teeth underwent immediate replantation. However, the incidence of IRR was lower in both treatment groups than in a control group. In their study, ankylosis was significantly lower in the Ledermix group than in the CH group, but the untreated control group did not differ significantly from either treatment group. This finding might have been related to the duration of extraoral storage of the extracted teeth (15 minutes), as well as the lack of contamination. In fact, it is possible that not all pulps became contaminated following extraction, and revascularization of the pulps was noted in 2 control teeth that were excluded from the analysis [37].

Bryson et al. [38] evaluated the effect of CH and Ledermix after 60 minutes of dry storage. Two-rooted premolars were first hemi-sectioned and then extracted and divided into 2 study groups. The authors dichotomized the outcomes into 1) favorable healing (presence of cementum over the dentin surface, whether previously resorbed or not) and 2) poor healing (including IRR or ankylosis). The authors concluded that the Ledermix-treated group exhibited significantly greater healing and less resorption than the CH-treated group.

However, a disadvantage of Ledermix paste is tooth discoloration, which has been reported to be significantly greater than observed with CH paste [3940].

In summary, in cases of immediate replantation, ankylosis was significantly lower when Ledermix was used compared to CH, although the occurrence of IRR did not differ significantly between the 2 treatments [37]. However, the studies in which CH and Ledermix were used for delayed replantation yielded conflicting results [3638].

In 2001, Levin et al. [16] soaked extracted dog teeth in an alendronate solution prior to replantation. This method was significantly satisfactory for the elimination of RR and resulted in better healing than when Hanks' Balanced Salt Solution without alendronate was used. This phenomenon might be attributable to the osteoclast inhibitory activity of alendronate [4142]. Thereafter, in 2007, Mori et al. [43] used alendronate as an intracanal therapeutic agent in rat teeth that underwent late replantation. When compared to a CH-treated group, the presence of RR was less evident in the alendronate-treated group at 30 days. However, these differences were not observed at 15 or 60 days. In general, CH and alendronate demonstrated similar behaviors.

In 2009, Thong et al. [7] conducted a study of avulsed monkeys' teeth using 2 intracanal medications (CH paste and etidronate disodium, a bisphosphonate) and a negative control group. IRR was significantly greater in the negative control group than in the 2 treatment groups, while ankylosis was significantly lower in the treatment groups; however, no significant difference was found between the CH and bisphosphonate groups. The lower amount of inflammatory resorption and inflammation of the periodontal ligament in the negative control group can be attributed to canal debridement prior to replantation, resulting in the removal of bacteria and pulp tissue debris. Thus, the inflammatory stimulus was less intense in the untreated control group. In the study of Thong et al., [7] the etidronate-treated group showed significantly worse overall outcomes than the CH group. Therefore, the authors concluded that intracanal bisphosphonate treatment did not yield a beneficial effect. The limited effect of bisphosphonate on RR and bone deposition might have resulted from limited penetration through the dentinal tubules to the root surface. Moreover, etidronate is more soluble than CH; thus, it cannot act as a reservoir for long-term use [7].

In 2002, Mori and Garcia [44] evaluated the possibility of using acetazolamide solution for the surface treatment of rat teeth that underwent intentional avulsion and delayed replantation. However, RR was observed in the specimens. Later, in 2006, Mori et al. [45] evaluated the effect of acetazolamide solution at a concentration of 10⁻⁵ M as an intracanal therapeutic agent in late replanted rat teeth. The results showed that CH paste limited RR, but did not prevent it. On the contrary, no RR was seen after 60 days in the acetazolamide-treated group, confirming the efficacy of acetazolamide in inhibiting RR. Thereafter, in 2013, Mori et al. [46] conducted a study with the same design, but with the introduction of acetazolamide in the paste form. The results demonstrated the potential of both intracanal substances—namely, acetazolamide paste and CH—to limit RR, although they were unable to completely prevent it. Replacement resorption lacunae were present in a greater proportion in the CH group at 60 days. It was concluded that the acetazolamide paste was more effective than CH in limiting RR. This can be explained by the mechanism of action of the active substance in the solution. Specifically, acetazolamide is known to be a potent inhibitor of carbonic anhydrase [4748], an enzyme presents in osteoclasts. This enzyme catalyzes the reaction between carbonic acid and water, leading to the formation of hydrogen ions [49], which are responsible for the decrease in pH in Howship lacunae [49]. Acidic conditions, in turn, liberate and activate other enzymes that participate in the resorption process [49]. Thus, carbonic anhydrase inhibition prevents this decrease in pH, making resorption unlikely.

Indomethacin is a non-steroidal anti-inflammatory medicament that is a potent inhibitor of cyclo-oxygenase, which is the first enzyme in the prostaglandin synthesis pathway. In a study by Zanetta-Barbosa et al., [50] it was hypothesized that indomethacin might serve as a bone resorption inhibitor, with the possible effect of preventing RR when used as an intracanal dressing in delayed tooth replantation. In their study, 24 teeth from 6 adult dogs were extracted, dried, and divided into 4 groups according to the root surface treatment protocols performed before replantation, and the intracanal medication was used after replantation. In group 1 (negative control), the root surfaces were treated by immersion in 0.9% saline solution. In the other groups, the roots were immersed for 10 minutes in CH (group 2), indomethacin (group 3), or a solution of indomethacin with CH (group 4). After 2 weeks, group 1 received a single-visit root canal treatment and obturation with gutta-percha and sealer consisting of zinc oxide and eugenol. The teeth in the other groups received intracanal medications with the same material used for immersion. At 45 and 90 days after replantation, the intracanal therapeutic dressings were changed. There was no significant difference amongst the groups regarding IRR and ankylosis. However, group 1 exhibited significantly more normal periodontal tissue than group 4. Total resorption was significantly greater in group 4 than in group 1. Therefore, based on their results, indomethacin was not recommended as a suitable intracanal dressing for replanted avulsed teeth.

Several studies have demonstrated that gallium nitrate has the potential to prevent bone resorption [5152]. Gallium nitrate has an inhibitory effect on osteoclasts [53], and it is incorporated into bone tissue, participating in the formation of fluorapatite; therefore, the newly formed bone becomes further resistant to the action of osteoclastic resorption [5152]. In 2000, Ghazi et al. [54] proposed the use of gallium nitrate as an intracanal dressing. In a quantitative in vitro study, they evaluated the amount of gallium nitrate that diffused through dentinal tubes to the periodontal space. The least amount exceeded the 10⁻⁴ M concentration required to inhibit osteoclastic activity [5455]. Subsequently, in 2006, Mori et al. [56] conducted an experiment to evaluate the effect of gallium nitrate solution as a root canal dressing in avulsed replanted teeth, in comparison to CH paste. They concluded that gallium nitrate solution and CH paste showed similar performance in general.

Enamel matrix–derived protein (Emdogain) has been used in periodontal regeneration techniques, and has shown meaningful results in promoting the formation of new bone, periodontal ligament, and cementum [5758]. The only study comparing CH with enamel Emdogain as an intracanal medication in replanted teeth was conducted by de Oliveira et al. [59] Quantification of resorption revealed that Emdogain-treated teeth showed a lower percentage of resorption (31.58%) than CH-treated teeth (80.48%). Elsewhere in the literature, Emdogain has been ascertained to be effective in stimulating the formation of acellular cementum on traumatized root teeth [60]. When applied on the root surface, these proteins resulted in the differentiation of mesenchymal cells into cementoblasts, osteoblasts, and fibroblasts.