6
Regeneration in Endodontics with Clinical Cases
Abhishek Parolia1,2, Maya Feghali3, and Catherine Ricci4
1 Department of Endodontics, University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, USA
2 School of Dentistry, International Medical University, Kuala Lumpur, Malaysia
3 Private Practice, Paris, France
4 University of Nice-Sophia Antipolis, Nice, France
6.1 Introduction
Regenerative endodontics has been defined as “the biologically based procedures designed to replace damaged structures, including dentin, root structures, as well as cells of the pulp‐dentin complex” [1]. Regenerative endodontics was introduced first by Nygaard‐Ostby in 1961, then revised by Iwaya et al. in 2001 [2]. Since then, many studies have been published showing favorable outcomes in terms of radiographic healing of periapical tissues, thickening and lengthening of dentinal walls, and apical closure [3, 4].
The regenerative procedure has been shown to be an alternative approach to the established apexification procedures for the treatment of permanent immature necrotic teeth as a result of caries, trauma, or development anomalies. Various intracanal medicaments (ICMs) including calcium hydroxide have been used for the apexification procedure. However, calcium hydroxide is not advocated any more because of the long time needed to create an apical barrier, weakening its effect on the thin dentin walls and, thus, increasing the susceptibility of cervical root fracture [5].
Current treatment protocols recommend the placement of mineral trioxide aggregate (MTA) plug to close the apical foramen. Although MTA induces a mineralized barrier apically, this approach does not allow further root maturation.
The new way of regenerative thinking seems to be promoted by the limitations of the use of calcium hydroxide or MTA apexification that consist in creating a physical barrier against which the root canal filling can be achieved without any improvement in root dimensions, and susceptibility to root fractures because of thin canal walls and poor root‐crown ratio [5].
Regenerative procedure based on the usage of stem cells, scaffold, and growth factors aims to repair and replace damaged tooth structures and restore normal pulp function in combination with regaining pulp connective tissue vitality in necrotic and infected teeth [6]. According to the American Association of Endodontics (AAE) [7], the degree of success of functional pulp regeneration is largely measured by parameters including elimination of symptoms and evidence of bony healing, increased root wall thickness and/or increased root length, and positive response to vitality testing for the tertiary goal ([7])
Different terms have been used to describe this procedure, such as regeneration, pulp revascularization, and revitalization. These techniques have been suggested to make use of the stem cells present at the apical area of immature teeth after induction of bleeding from the periapical tissue. The blood clot formation has been shown to allow repopulation of the root canal with vital tissues and promote continued deposition of hard tissue and further root development by the deposition of mineralized tissue [5].
This regenerative technique, commonly known as the regenerative endodontics procedure (REP), is based on the following prerequisites [5]:
- Presence of stem cells
- Complete disinfection of the root canals
- Provision of a scaffold within a root canal
- Provision of a signal to the stem cells so that they can differentiate
Stem cells of the apical papilla (SCAP) have been shown to play a major role in regeneration techniques. Stem cell population growth into the root canal system is achieved mainly through induction of bleeding from the periapical area. This has been supported by the work of Lovelace et al. [8] who showed a 400‐ to 600‐fold increase in mesenchymal stem cell markers in blood collected from root canals in comparison to the levels found in systemic blood samples. Apical papilla cells differentiate into root primary odontoblasts and promote root dentin formation by continuing their normal physiological development after revascularization procedures [9]. Although the exact nature of the tissue repopulating the root canal system is still unclear, histological studies have reported fibroblasts, blood vessels, collagen, cementoblasts and osteoblasts, and pulp‐like tissue in the repopulating tissue [9].
6.2 Factors Affecting the Clinical Outcome of REP
6.2.1 Etiology
The etiology or cause of the pulpal necrosis or apical periodontitis has shown to influence the outcome of REPs. Caries, trauma (30%), or development anomalies including dens evaginatus (22%) [10] have been the main causes of permanent immature teeth developing necrosis and apical periodontitis and, thereby, treated by REP [10].
REPs performed to treat cases with dens evaginatus have shown to have better prognosis than cases with trauma as a cause for the pulpal damage [10]. This could be explained by the fact that trauma to the tooth structure can lead to the induction of root resorption and cause damage to the Hertwig’s epithelial root sheath and apical papilla, thus affecting the outcome of REP negatively [9].
The vast majority of failed REP cases were diagnosed with necrotic pulp and some form of apical pathosis. The presence of established periapical pathosis in cases of a necrotic pulp with an immature apex may render the disinfection of these cases more challenging and less predictable. Various studies have observed and demonstrated a relationship between the duration of pulp necrosis and the outcome of REP [11]. Similarly, Vishwanat et al. [12] found a significant association between the presence of periapical radiolucency and the lack of increased root wall thickness due to the residual bacterial biofilms modifying the osteogenic differentiation of stem cells from the apical papillae.
6.2.2 Type of the Tooth
The establishment of REPs constitutes an adequate treatment option for immature single‐rooted necrotic teeth with apical periodontitis. However, there is little evidence for the complete acceptance of REP as a predictable and reproductible treatment option in posterior immature teeth with pulpal necrosis and apical periodontitis [13, 14].
In addition to the type of the tooth, the size of the apical foramen/opening has been considered a significant predictor factor for the success of REP. Better outcome is noted when the size of the apical foramen ranges between 0.5 and 1 mm [13].
6.2.3 Induction of Bleeding and Blood Clot
The evoked‐bleeding step in REPs triggers the significant accumulation of undifferentiated stem cells into the root canal space as shown by [8], where these cells might contribute to the regeneration of pulpal tissues.
Once the blood clot is formed after the induction of bleeding, it acts as a physical scaffold for the three‐dimensional organization of the newly formed tissue and releases necessary stem cell population growth factors for cell growth and cell differentiation [15].
Although the bleeding induction during REP is a critical step, the outcome of it remains unpredictable. Multiple cases have reported difficulties initiating bleeding even after the use of vasoconstrictor‐free anesthetic solution[10, 11]. Furthermore, some studies, despite the lack of bleeding induction, have shown radiographic continuing of thickness of canal walls and apical closure [10, 16].
Digka et al. [17] did not observe any significant differences in the histological outcome with the success or failure to induce apical bleeding and a blood clot formation, and, in fact, concluded that the periapical tissues may be injured during the apical bleeding procedure with an endodontic file. Therefore, the bleeding induction step may not be a clear predictor to determine the outcome of REP.
6.2.4 Disinfection of the Root Canal System
Thorough disinfection of the root canal system plays a crucial role in the success of REPs. Various irrigants and ICMs have been attempted to achieve thorough disinfection.
Sodium hypochlorite (NaOCl) has been used with different concentrations as the only irrigation solution, or in combination with other irrigants for REPs. Despite the fact that this irrigant has been shown to have a potent antimicrobial action that dissolves organic matter at concentrations superior to 3%, it is probably cytotoxic to periodontal ligament cells and stem cells of apical papilla [5, 15]. For this reason, clinical considerations of the AAE recommend the use of lower concentrations of NaOCl in REPs [18].
In some publications, chlorhexidine (CHX) in addition to NaOCl has been used to disinfect the root canal system because of the antimicrobial activity and substantivity of CHX. The use of CHX and NaOCl should not be recommended because it leads to the formation of a cytotoxic orange precipitate named Para‐Chloroaniline [19, 20]. Additionally, 2% CHX solution has been found to induce serious cytotoxic effects on stem cells, so clinicians should avoid using it as the final irrigant in REPs [15, 21].
The use of NaOCl solution followed by EDTA is now widely recommended [10]. It has been shown that EDTA promotes greater survival of the SCAPs and the release of trapped stem cells from the dentin [21]. In another study, [22] found that EDTA used for final irrigation partially countermands the effect of high concentrated NaOCl on the survival of stem cells. EDTA helps create a microenvironment in root canals that promotes the survival/proliferation and the differentiation of SCAPs, and has a positive impact on the outcome of REP [10, 22].
Various ICMs have been tried and tested in REPs, however, triple antibiotic paste (TAP) (100 mg metronidazole, 100 mg minocycline, and 100 mg ciprofloxacin) has been shown to have efficient bactericidal effect and potency to eradicate microorganisms from the infected dentin of root canals. Lately, the use of minocycline has been eliminated from the TAP to avoid potential tooth discoloration [23].
6.2.5 Coronal Barrier
A poor coronal seal can have a negative impact on the outcome of REPs. Achieving a good coronal seal is of utmost necessity in maintaining a sterile root canal environment, preventing future contamination and, thereby, failure of the procedure.
Nowadays, several materials such as MTA, Biodentine and bioceramic‐based ready‐to‐use materials are gaining popularity in providing a coronal seal because of their advantages, including biocompatibility and tissue‐conductive properties. Glass ionomer cements (GICs) or composite resin are placed above the MTA‐based materials to ensure a hermetic seal [24, 25].
6.3 Materials used for REP
NaOCl at a concentration between 1 and 2.5% can be used as the main solution for irrigation. However, biocompatibility considerations should be considered to protect any vital remnants of SCAP.
In addition to NaOCl, EDTA has been found to offer advantages by increasing the survival ability of the stem cells and releasing growth factors trapped within the dentin matrix [13]. EDTA conditioning of the dentin promotes cell adhesion, migration, and differentiation toward the dentin [26]. Thus, EDTA irrigation as a final rinse before the induction of bleeding was likely to act favorably on the formation of new mineralized tissue [13, 26].
Various ICMs including calcium hydroxide and TAP have been used to disinfect the root canals in REPs with no differences observed in terms of treatment outcomes [27, 28].
Calcium hydroxide as an ICM has been historically used to induce the formation of a hard tissue barrier at the root apex because of its antimicrobial activity, high pH, or its direct effect on the periapical soft tissues [28, 29]. However, there are several limitations relating to its use, such as the long time required for hard tissue barrier formation, possibility of root canal contamination during the process, multiple, repeated dressings, and patient’s compliance. Additionally, long‐term application of calcium hydroxide may affect the dentinal structure and reduce the fracture resistance of teeth.
MTA has gained popularity amongst clinicians over the years. The principal components of MTA powder include tricalcium silicate, tricalcium aluminate, tricalcium oxide, and silicate oxide, and liquid can be distilled water or saline.
MTA has multiple benefits compared to calcium hydroxide as the apexification procedure can be completed in one or two visits with no dependence on the patient’s compliance, and greatly reducing the risk of reinfection of the tooth and fracture [4]. It also possesses high radiopacity, less solubility, good antimicrobial property, and high biocompatibility, bioactivity, and regenerative potential. However, ProRoot MTA has some limitations as well, including high cost, long setting time (70–175 minutes) and difficulty handling.
Therefore, a few other alternatives such as Biodentine (Septodont, Saint‐Maur‐des‐Fosses, France), and OrthoMTA (BioMTA, Seoul, Korea) can also be tried to manage these kinds of cases.
Biodentine contains tricalcium silicate as a core material and calcium chloride in liquid form. It has a few major advantages over MTA, including fast setting time (6–10 minutes), high compressive strength (100–300 MPa), and flexure strength (34 MPa). However, the radiopacity of Biodentine is lesser (3.5 mm of equivalent thickness of aluminum) than MTA (7 mm of equivalent thickness of aluminum). It also possesses less solubility, good antimicrobial property, and high biocompatibility, bioactivity, and regenerative potential similar to MTA [30, 31].
OrthoMTA, popularly known as grafting material, has similar composition to MTA with less heavy metal contents than MTA. It also possesses similar properties like MTA and Biodentine with a setting time of 180–360 minutes. It forms an interfacial hydroxyapatite layer between OrthoMTA and the root canal wall and prevents microleakage. It also creates intratubular mineralization and entombs the remaining microorganisms [32, 33].
6.4 Key Points to Remember While Performing REPs
- A permanent tooth with an open apex poses a different set of challenges compared to the tooth with a mature root apex.
- Incomplete root and thin dentinal walls make the tooth more susceptible to fracture, and compromised crown to root ratio may cause increased mobility.
- Owing to the presence of fracture‐prone thin dentinal wall, disinfection of the root canal system relies solely on chemical disinfection using irrigants and ICM.
- Careful selection of irrigants/ICMs is imperative to ensure successful outcomes. Calcium hydroxide/TAP/2% chlorhexidine can be used as an intracanal medication. However, each ICM may have its limitations.
- Extrusion of instruments/irrigants/ICMs and obturating material can lead to inflammation of periapical tissues and delay the healing process.
- To prevent extrusion of irrigants into periapical tissue, irrigating system with a negative pressure system such as an EndoVac or GentleWave system is recommended. Close‐ended, single side vented needle should be used if positive pressure technique is used while irrigating the canal in open apex cases.
- Careful working length determination through an apex locator and reconfirming it with the intraoral periapical radiograph (IOPA) is recommended in open apex cases.
- Although MTA has been the material of choice because of its biocompatibility, it takes a long setting time, and a waiting period of a few hours may be needed after the placement of MTA to achieve hard set mass. An alternative fast‐setting Biodentine material can be used.
- A very specific disinfected environment must be created in the root canal space for revascularization of the pulp to take place. A combination of antibiotics – specifically ciprofloxacin, metronidazole, and minocycline – has been shown to properly kill common endodontic pathogens in the infected root canal. The blood clot can be created by instrumenting the tooth beyond apex to approximately 1–2 mm to permit bleeding into the root canal system.
- Multiple theories for the mechanism of revascularization have been proposed and discussed. Current protocol of REP suggested by the AAE presents with its own sets of limitations. Therefore, careful case selection is imperative in determining case success.
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