Australian Dental Journal

Transcription

1 Australian Dental Journal The official journal of the Australian Dental Association Australian Dental Journal 2016; 61:(1 Suppl): doi: /adj Management of incompletely developed teeth requiring root canal treatment SC Harlamb* *Specialist Endodontist, Private Practice, Burwood, New South Wales, Australia. ABSTRACT Endodontic management of the permanent immature tooth continues to be a challenge for both clinicians and researchers. Clinical concerns are primarily related to achieving adequate levels of disinfection as aggressive instrumentation is contraindicated and hence there exists a much greater reliance on endodontic irrigants and medicaments. The open apex has also presented obturation difficulties, notably in controlling length. Long-term apexification procedures with calcium hydroxide have proven to be successful in retaining many of these immature infected teeth but due to their thin dentinal walls and perceived problems associated with long-term placement of calcium hydroxide, they have been found to be prone to cervical fracture and subsequent tooth loss. In recent years there has developed an increasing interest in the possibility of regenerating pulp tissue in an infected immature tooth. It is apparent that although the philosophy and hope of regeneration is commendable, recent histologic studies appear to suggest that the calcified material deposited on the canal wall is bone/cementum rather than dentine, hence the absence of pulp tissue with or without an odontoblast layer. Keywords: Apexification, immature teeth, regenerative endodontic procedure, root canal, trauma. Abbreviations and acronyms: CEJ = cemento-enamel junction; CMCP = camphorated para-chlorphenol; HERS = Hertwig s Epithelial Root Sheath; IADT = International Association of Dental Traumatology; MTA = mineral trioxide aggregate; PDL = periodontal ligament; PLP = plasma-rich plasma; REP = regenerative endodontic procedures; SCAP = stem cells from the apical papilla; TAP = triple antibiotic paste. INTRODUCTION The incompletely developed permanent tooth, following a traumatic injury, provides the clinician with diagnostic and clinical challenges. Endodontic treatment, if indicated, poses instrumentation and obturation issues due to the wide canal and thin dentinal walls, and as such the decision to commit the tooth to endodontic treatment should be based on definitive findings and sound biological principles. Studies have shown that the endodontically treated immature tooth is more prone to fracture 1 than its fully developed root filled counterpart, and as such there is presently an abundance of researchers exploring the notion of continued root development of the immature tooth with a necrotic and infected pulp. Until recently, when asked to present a review on the endodontic management of the immature tooth, the author would discuss and describe techniques such as conservative pulp therapy (apexogenesis) or apexification. There would be an outline of indications, techniques, follow-up and outcomes. Rafter s review in 2005 was an excellent example and even included the then exciting, relatively new material known as mineral trioxide aggregate (MTA). 2 In 2015, however, preparing such a paper is not so straightforward. Despite Nygaard-Østby s 3 work in the 1960s, which showed the possibility of the growth of connective tissue into the pulp space following formation of a blood clot, the concept of pulp regeneration remained relatively quiet (and ignored) until the turn of the century. Since then, there have been an abundance of case series and reports with at least 35 papers 4 dealing with pulp regeneration published between 2007 and 2013, reflecting a mounting interest in the possibility of continued root development in the infected immature tooth. This review will explore the impact of trauma on the immature tooth, as well as endodontic treatment options such as pulpotomy and apexification and the roles of calcium hydroxide and MTA. Regenerative procedures will also be discussed and the current treatment protocol outlined Australian Dental Association 95

2 SC Harlamb Although an immature tooth may require endodontic intervention due to caries or congenital anomalies such as dens invaginatus, it is important to note this review will deal with the endodontic management of the trauma-afflicted immature permanent tooth. Trauma and the incompletely developed tooth Studies have revealed that 30% of children are affected by a traumatic dental injury, with the majority occurring before complete formation of the root. 5 Prior to commencement of endodontic treatment, careful assessment, both clinical and radiographic, is essential. The clinician should be mindful that, if possible, every attempt should be made to preserve pulp integrity in the incompletely developed mature tooth. As such, the type of trauma the permanent immature tooth has been subjected to plays an essential role in formulating a treatment plan. Avulsion injuries, fractures and luxation injuries all have vastly differing impacts on both the pulp and periodontal ligament (PDL), and subsequently need to be individually considered. Avulsion injuries and the immature tooth The majority of avulsion injuries occur between the ages of 8 to 12 years. 6 Following an avulsion injury, severe damage is inflicted upon both the pulp and periodontal attachment. As a result of the tooth being separated from its socket, viable PDL cells are present on both the root surface as well as the socket wall. Therefore, the timing of replantation of the avulsed tooth is critical. The avulsed immature permanent tooth has the added complications of its shortened root and thin walls, and the impact these will have on its long-term prognosis. The time that an avulsed tooth is out of its socket 7 is critical and therefore should be considered as follows: Extraoral dry time MORE than 60 minutes Following an avulsion injury, a tooth with a dry time in excess of 1 hour will have virtually no viable PDL cells on its root surface. 8 It has been concluded that the 60-minute mark of dry time is the critical point at which PDL cell damage occurred. At 2 hours, there were no viable cells present on the root surfaces. 8 As a result, the management of the avulsed immature tooth with a dry time in excess of 1 hour is complex to replant or not? Some argue that the prognosis for such teeth is so poor that replantation will lead to probable replacement resorption and ankylosis with all the well-known complications (difficulties with extraction, impact on marginal bone, etc.) 6 ensuing. Conversely, others argue that replantation will allow for maintenance of both the alveolar height and width, hence ensuring easier implant placement once the child has fully developed. 9 Malmgren and coworkers 10 in 1984 introduced decoronation as a treatment alternative to extraction of the ankylosed tooth they argued that removal of the ankylosed tooth would lead to severe bone loss, thereby compromising implant placement. The technique involved removal of the crown at the cementoenamel junction (CEJ), encouraging bone deposition over the resorbing root. The authors argued that such a technique supports the indication for replantation of avulsed teeth in children even when the extra-alveolar conditions indicate that healing might be compromised by ankylosis. 6,11 The recently revised International Association of Dental Traumatology Dental Trauma Guidelines 11 confirm the prognosis for such teeth is poor with resorption and ankylosis to be expected. However, replantation is recommended (delayed replantation) for aesthetic, functional and psychological reasons and to maintain alveolar contour. 11 Extraoral dry time LESS than 60 minutes If stored ideally (physiological storage media such as milk, saline, saliva or HBSS) or extraoral dry time of less than 60 minutes, it is generally accepted that pulp revascularization and continued root development is possible. Andreasen et al., in their seminal 1995 series of papers 12 examined the pulp and periodontal responses of 400 replanted incisors which included 28 teeth with incompletely developed roots. In 34% of the immature teeth, following replantation, spontaneous revascularization occurred, a finding consistent with a study years earlier. The authors hypothesized that Hertwig s Epithelial Root Sheath (HERS) can tolerate the trauma of avulsion and replantation plus damage due to extra-alveolar storage. 12,14 Therefore, as opposed to the replanted fully matured tooth, endodontic treatment for the immature replanted tooth should be initially avoided any opportunity for continued root growth in these cases will be lost if endodontic treatment is initiated. 14 Follow-up and review is critical it is recommended that the patient be reviewed at 4 weeks, 3 months, 6 months, 1 year and yearly 15 thereafter for pulp sensibility testing and clinical and radiographic examination. Carbon dioxide (CO 2 ) has been found to be extremely reliable in assessing pulp status, even in immature teeth. 16 The clinician should be aware of any radiographic changes such as apical breakdown or root resorption, as well as clinical findings such as tenderness to percussion and palpation. However, the decision to commence endodontic treatment must be based on a holistic approach, ensuring all the clinical and radiographic findings have been considered and accurately interpreted Australian Dental Association

3 Management of incompletely developed teeth Luxation injuries and the immature tooth Luxation injuries are the most prevalent of all traumatic dental injuries, comprising 15 61%. 17 Five types of luxation injuries have been identified: concussion, subluxation, extrusive luxation, lateral luxation and intrusive luxation. In teeth with closed apices, studies have consistently confirmed that the more severe the luxation injury, the greater the prevalence of pulp necrosis. For example, 3% of teeth with a concussion type injury exhibited pulp necrosis while 85% of intrusively luxated teeth had necrotic pulps. 18 Immature teeth are less likely to develop pulp necrosis following a luxation injury according to Andreasen and Vestergaard Pedersen, 18 only 8% of immature luxated teeth exhibited pulp necrosis over a 10-year period, as opposed to 38% of luxated teeth with closed apices while root development was the only significant factor in predicting healing following a luxation injury. 18 It was also found that the wider the diameter of the apical foramen, the higher the probability of pulp survival. 19 Researchers have surmised that the greater the width of the apical foramen, the easier it is for revascularization to occur. 19 Additionally, the type of luxation injury an immature tooth is subjected to does not have the same impact on pulp necrosis developing when compared to the closed apex tooth. Therefore, it is imperative to carry out all appropriate testing prior to commencement of endodontic treatment for the luxated immature tooth. The clinician should be mindful that colour change, a negative response to pulp sensibility testing and indeed a radiographic apical radiolucency can all be followed by pulp repair, especially given the immature tooth s propensity for pulp revascularization. Andreasen 20 has concluded that tenderness to percussion is the only clinical sign which can be consistently relied upon as an indicator of pulp necrosis and infection. Management of the intrusively luxated immature tooth Intrusive luxation, the displacement of a tooth (along its long axis) into the alveolar socket, is considered the most severe of all the luxation injuries. 21 An associated fracture of the alveolar socket is also commonly seen. Studies have shown that the survival of intrusively luxated teeth (whether fully developed or not) range from 69% to 95%. 21 Irrespective of root development, 30% of all intruded teeth are lost after 15 years. 22 Following intrusive luxation, the stage of root development plays a major role in determining the potential outcome of pulp necrosis, root resorption and loss of marginal bone. Complications have been found to be significantly less in the immature tooth following intrusive luxation researchers have hypothesized a reason for the more favourable outcome is the softer bone, thereby ensuring the impact of the intrusion on the PDL to be significantly less in the growing patient. 22 The challenge associated with intrusive luxation has for many years been its clinical management. Three options are available to the clinician in the management of the intruded tooth: (1) await spontaneous re-eruption; (2) immediate surgical reduction and fixation; or (3) orthodontic repositioning. 23 Until recently, 24 the management of intrusive luxation injuries received very little attention in the literature, 23 primarily due to it being a rare dental injury (0.5% to 1%). 25 However, Andreasen et al. in have provided specific guidelines as to management of the intrusively luxated tooth the stage of root formation and the age of the patient greatly assist the clinician in the decision-making process. The authors concluded that allowing the permanent immature tooth to spontaneously re-erupt is the treatment of choice, so long as the tooth is not completely embedded. If no crown is visible, then the incisal edge should be surgically exposed and the crown loosened slightly with forceps to facilitate re-eruption, which can take up to 6 months (the authors reported a range of 2 to 14 months). 24 Figures 1 to 3 illustrate an example of spontaneous re-eruption of an intrusively luxated open apex tooth 21 in a 10-year-old patient. The patient was monitored for 7 months with continued evidence of re-eruption. Endodontic treatment was eventually deemed necessary for the intrusively luxated tooth 21 because the root canal system had become infected, and this was commenced following complete eruption of the tooth. 23 If the clinician decides to allow for re-eruption, a follow-up and review plan must be formulated with the patient and parent/carer. The author recommends review at 2, 4, 8 and 12 weeks initially. At each appointment, mobility and percussion testing should be carried out as well as pulp sensibility tests, preferably with CO Guidelines currently advise radiographs to be taken at 2 3 weeks, 6 8 weeks, 1 year and 5, 10 and 15 years. 11 During the observation period it is imperative to note any signs of pulp necrosis and infection, and inflammatory root resorption endodontic treatment will then need to be commenced as soon as practical but as per other luxation injuries and the immature tooth, endodontic treatment should only be initiated if absolutely indicated. A common concern for the clinician is if the intruded tooth is not showing any signs of re-eruption or the possibility of ankylosis. It is recommended that if there is no indication of re-eruption after one month then the crown should be loosened with forceps and the tooth orthodontically repositioned Australian Dental Association 97

4 SC Harlamb Fig. 1 Intrusive luxation of immature tooth 21 of approximately 2 3 mm with crown clinically visible. (Reproduced from Harlamb SC, Messer HH. Endodontic management of a rare combination (intrusion and avulsion) of dental trauma. Dent Traumatol 1997;1:42-46, courtesy John Wiley and Sons.) Fig. 3 Fourteen months post-trauma with associated periapical healing of tooth 21. (Reproduced from Harlamb SC, Messer HH. Endodontic management of a rare combination (intrusion and avulsion) of dental trauma. Dent Traumatol 1997;1:42-46, courtesy John Wiley and Sons.) widened canal and open apex should allow for pulp healing, the clinician should be mindful that endodontic treatment is commonly indicated for the intrusively luxated tooth. Fig. 2 Seven months post-trauma with clinically acceptable re-eruption of tooth 21. Note the apical radiolucency and tooth was non-responsive to CO 2 testing. (Reproduced from Harlamb SC, Messer HH. Endodontic management of a rare combination (intrusion and avulsion) of dental trauma. Dent Traumatol 1997;1:42-46, courtesy John Wiley and Sons.) In conclusion, current guidelines stipulate that if a tooth with incomplete root formation is intrusively luxated then the clinician should expect a favourable response with spontaneous re-eruption. Although the The crown fractured immature tooth The management of a pulp exposure of an immature tooth following crown fracture (complicated crown fracture) has long been recommended to be conservative in nature. Cvek 27 has stated that the exposed vital pulp should be maintained in young teeth with incomplete root formation and that premature removal of the pulp deprives the tooth of adequate root development. In a clinical study where patients aged 7 to 16 were examined over 12 hours following a complicated crown fracture, the primary pulp response observed was hyperplastic in nature 28 whereas following a mechanically induced pulp exposure, researchers found no evidence of necrosis, other than a superficial inflammatory response of no more than 2 mm. 29 These findings served as the basis for the development of the Cvek partial pulpotomy, a technique designed to maintain the integrity of the pulp by surgically removing the coronal portion of the pulp, thereby ensuring continued root development in the immature tooth. Calcium hydroxide was the material of choice proposed by Cvek he recommended cutting a cavity Australian Dental Association

5 Management of incompletely developed teeth approximately 2 mm below the site of the pulp exposure, establishing haemostasis and then covering the wound with calcium hydroxide to promote hard tissue formation. MTA has recently been proposed as an alternative material to calcium hydroxide in partial pulpotomy cases, the main advantages being that complete haemostasis need not be achieved as MTA requires fluid to be present to set and that once set, MTA acts as a barrier against bacteria penetration. 30 Both calcium hydroxide and MTA will be discussed in detail below. Apexification The American Association of Endodontists defines apexification as a method to induce a calcified barrier in a root with an open apex or the continued apical development of an incompletely formed root in teeth with necrotic pulps. 31 Endodontic management of an immature tooth is justifiably described as challenging for three fundamental reasons: 7 (1) The open apex creates a difficult environment for controlling the root canal filling material to be used. (2) Due to the width of the canal and the thin root dentine walls, it can be extremely difficult to adequately clean the canal, as an aggressive instrumentation approach is contraindicated. (3) The remaining canal walls are inevitably quite thin and therefore there exists a high degree of possibility of root fracture. Two types of apexification procedures have been described: calcium hydroxide (multiple visit) apexification and MTA apical barrier (single visit) apexification. Calcium hydroxide (multiple visit) apexification Calcium hydroxide has played an integral role in dentistry since first described by Hermann 32 in 1930 as a pulp capping agent. Since then numerous studies have been carried out confirming its bactericidal efficacy and in turn its ability to promote healing and the formation of a hard tissue barrier. These effects are directly related to calcium hydroxide s alkaline ph of 12.5, which enables it to cause localized tissue necrosis, allowing inflammatory cells to migrate to the area, thereby pre-empting wound healing. It has also been found that 99.9% of common bacterial flora within an infected root canal system are killed when they come into contact with calcium hydroxide. 33 Calcium hydroxide also has the ability to dissolve necrotic pulp tissue, 34 which therefore allows the clinician to minimize filing (see below). Calcium hydroxide s ability to promote a hard tissue barrier (i.e. whether it has osteogenic properties) remains uncertain. However, it is generally accepted that the apical placement of calcium hydroxide within the root canal of a tooth with an open apex elicits a response similar to when it comes into contact with coronal pulp tissue. Rather than dentine being formed however, reparative or cementum-like hard tissue has been identified. 35 Frank first described the calcium hydroxide apexification technique 36 in 1966 following Kaiser s 37 presentation 2 years earlier which combined calcium hydroxide with camphorated para-chlorphenol (CMCP). Frank advocated the placement of calcium hydroxide with CMCP, with the calcium hydroxide to be replaced every 3 months until an apical barrier was formed which could take up to 24 months. The calcium hydroxide apexification technique is simple. Once working length is established radiographically, light filing is advocated with copious irrigation using 0.5% sodium hypochlorite (NaOCl) 33 to facilitate the removal of necrotic pulp tissue. Sterile paper points must be used to dry the canal followed by placement of calcium hydroxide, which can be mixed with saline, sterile or distilled water. 2 Pulpdent â calcium hydroxide mixed with methylcellulose has been proposed by Heithersay 38 and Feiglin. 39 An adequate interappointment temporary restoration is a critical, yet often overlooked, step in the apexification procedure, as it is essential the medicament remains within the canal without any possibility of bacterial ingress. 41 Abbott 41 has recommended replacement of the calcium hydroxide every 2 to 3 months, usually over 5 to 6 appointments. A single application of calcium hydroxide may lead to the medicament washing out, hence the possibility of delayed healing (Fig. 4). 41 The apical barrier, Abbott also argues, can only be accurately assessed clinically tapping a sterile paper point apically provides the clinician with an idea of the integrity of the barrier. If blood or exudate are detected, then the calcium hydroxide needs to be replenished and further assessment indicated. Radiographs alone are not an accurate indicator of barrier formation. 41 Chawla 42 has suggested that calcium hydroxide needs to be placed only once as the author states there is no benefit in multiple applications of the medicament. However, this approach generally leads to much longer treatment times and it is not possible to ascertain when the root filling can be done. Once the clinician is satisfied with apical barrier integrity, calcium hydroxide should be placed one final time and left in situ for a further 3 months the canal can then be obturated, usually with a heat softened gutta-percha technique. As apexification with calcium hydroxide is the most established of all the techniques, its long-term success 2016 Australian Dental Association 99

6 SC Harlamb Therefore, although some disadvantages do exist with the multiple visit calcium hydroxide apexification technique, the clinician should bear in mind it is, to date, a technique which has been scrutinized and assessed for many years. It is a reliable and simple technique to carry out and therefore should not be readily dismissed as newer materials or techniques are proposed the clinician should continue to consider and offer it as a treatment option. Fig. 4 Calcium hydroxide washed out in the apical half of the canal of tooth 11 after 3 months it has therefore been recommended calcium hydroxide be replaced at 3 monthly intervals in apexification cases. (Reproduced from Abbott PV. Apexification with calcium hydroxide when should the dressing be changed? Aust Endod J 1998;24:27-32, courtesy John Wiley and Sons.) rates are well documented. Ballesio et al. 43 reported success rates of up to 90% with a follow-up of 7 to 13 years, while Heithersay 38 and Cvek 44 reported success rates above 95%. Cvek observed no difference in periapical healing between calcium hydroxide treated mature and immature teeth after 4 years. 1 Equally, disadvantages have been identified with the calcium hydroxide apexification method. Multiple appointments for replenishment of calcium hydroxide do pose problems for the clinician. Managing a child over numerous appointments can be challenging while the literature is replete with evidence that children may be traumatized in an ever-increasing manner when subjected to multiple appointments. 45 Apexification does not promote continued root development while calcium hydroxide has been shown to cause dentine brittleness via its proteolytic and hygroscopic properties. 46 Andreasen et al. 47 reported that long-term calcium hydroxide dressings could increase the risk of root fracture, hypothesizing that the high ph produced by the hydroxyl ions have a detrimental effect on the organic support (denaturation and dissolution of protein) of dentine. Cvek reported a high incidence of fracture (specifically at the cervical portion of the root) in the immature tooth following long-term calcium hydroxide applications. In teeth with very early root development, a fracture rate of 77% in 26 teeth was observed which fell to 2% in 362 mature teeth. 1 MTA apical barrier (single visit) apexification MTA was initially proposed as an apical plug in apexification cases in The authors at the time suggested that following 1 week with calcium hydroxide dressing, 3 4 mm of MTA be placed apically with pluggers and paper points. Over the ensuing years the technique has evolved into a single visit treatment. As will be shown, subsequent studies have shown very little difference in success rates between the single visit and multiple visit techniques. MTA is composed of calcium silicate, bismuth oxide, calcium carbonate, calcium aluminate and calcium sulfate, and when mixed with water or saline is made up of 33% calcium, 49% phosphate, 2% carbon, 3% chloride and 6% silica. 49 MTA takes up to 3 hours to set, has excellent sealing properties, is biocompatible and has the ability to set in a moist environment. 50 Additionally, when set MTA comes into contact with fluid, calcium hydroxide is released. Friedland and Rosado 51 deduced that this was the reason that MTA formed a hard tissue barrier similar to calcium hydroxide. As a result, MTA has been proposed as an excellent material in apexification cases. The MTA apexification technique is more challenging than the calcium hydroxide technique previously described. Following light filing and copious irrigation with 0.5% sodium hypochlorite and 17% EDTA, the canal is dried with sterile paper points. The MTA, once mixed to the correct consistency, can be dispensed on an MTA block (Fig. 4) and the material placed into the middle to apical third of the canal with a Half Hollenbach instrument (Fig. 5). The MTA can then be compacted to the correct working length with large paper points or loose fitting pluggers (pre-measured). It is advisable to place a moist cotton pellet against the MTA which should be left in situ for at least 6 hours. 7 Advocates of the MTA single visit technique place a bonded composite resin material directly over the MTA, filling both the canal and access opening. 50 However, such an extensive restoration would likely render the tooth impossible to retreat. There is no doubt that MTA offers many advantages when utilized in apexification procedures. However, it does have poor handling characteristics, being Australian Dental Association

7 Management of incompletely developed teeth structure and thin dentinal walls continue to be a clinical concern. Ongoing research appears to indicate that resin-bonded restorations within the canal and beyond the CEJ do act to reinforce these fracture prone teeth. 52 Fig. 5 MTA is placed into the slots of the MTA block. Fig. 6 MTA is placed on a Half Hollenbach to allow for ease of placement into the canal. heavily reliant on correct mixing techniques and its long setting time is a concern in the single visit technique as the clinician is unable to observe whether the material has set. Control of placement of MTA is difficult while both grey and white MTA have been found to discolour teeth. Another limitation with MTA is the difficulty the clinician is faced with if it needs to be removed. Witherspoon et al., 50 in a retrospective study, analysed the success rates of 144 immature teeth which were treated with an MTA apical plug over one (92/144) or two visits (52/144). The group in the twovisit category had calcium hydroxide placed for 3 weeks prior to the MTA plug being placed. Both groups achieved high success rates of over 90% following recall of at least 12 months However, with only 39.7% of the two-visit group being recalled as opposed to 60.3% of the single visit group, it is difficult to conclude much more than both techniques worked well in the short-term period. As can be seen, apexification procedures over the years have been successful in retaining the traumatized immature tooth. However, regardless of the technique or material employed the remaining tooth Regenerative endodontic procedures and the incompletely developed tooth where are we? The disadvantages associated with apexification discussed above have led, over the past 10 to 15 years, to increasing interest in the possibility of regenerating pulp tissue in the immature tooth with an infected necrotic pulp, thereby allowing for continued root development. This new frontier of regenerative endodontics has been met with either extreme enthusiasm 4,53 or scepticism. 54,55 There also appears to be a distinct lack of consensus regarding a title. At last count, the author has identified at least 7 descriptors: pulp regeneration; 53 pulp revascularization; 56 maturogenesis; 57 pulp revitalization; 58 pulp replacement; 59 pulp repair; 60 or most recently regenerative endodontic procedures (REPs). 4 A factor in this lack of consensus is that there is little agreement as to what is actually being regenerated and the impact that this tissue has (and will have) on the remaining tooth structure. 54 Nygaard-Østby 3 in 1961 found that following the creation of a blood clot in an infected root canal, tissue ingrowth was established. It was, however, not pulp in origin, rather it was consistent with fibrous connective tissue and cementum. As previously stated, the concept of pulp regeneration remained relatively quiet until recently, followed by ongoing hysteria amongst researchers multiple papers (152 case reports and case series) 4 dealing with pulp regeneration have been published, with claims that with pulp regeneration, a paradigm shift in the management of the infected immature tooth has been created. 53 REPs are defined as biologically based procedures designed to replace damaged structures, including dentine and root structures, as well as cells of the pulp-dentine complex. 4 Mesenchymal stem cells were identified within the apical papilla of immature teeth 61 and have subsequently been coined stem cells from the apical papilla (SCAP), which in turn have been found to differentiate into odontoblast-like cells (in vitro). 61 Therefore, the hypothesis of the REP is that undifferentiated cells within the apical papilla of an immature tooth can be stimulated to assist in the further development of the root and that for the procedure to succeed, all bacteria must have been eliminated, a scaffold is established apically to allow for ingrowth of new tissue and that a barrier and restoration ensures no bacterial recontamination. 62 Being an immature tooth, it was recommended that virtually no mechanical instrumentation be carried 2016 Australian Dental Association 101

8 SC Harlamb out and as such research was conducted to identify a new disinfection medicament which could effectively disinfect the canal and have no deleterious effect on the root dentine or any undifferentiated cells in the apical region. Hoshino et al. 63 found the combination of ciprofloxacin 200 mg, metronidazole 500 mg and minocycline 100 mg to be effective in eliminating bacteria from infected dentine the combination has become known as triple antibiotic paste (TAP). For cells and vasculature to proliferate in any regenerative procedure, a scaffold is required in the immature tooth researchers have found that the creation of a blood clot serves as a scaffold which then allows for stimulation of cell growth as well as possible odontoblast-like cells forming. 64 As it is imperative that the clot/scaffold remain free of bacterial contamination, a barrier needs to be placed and MTA has been found to be the most reliable material for this. As previously mentioned, interest was renewed with REPs following two case reports published in and 2004, 66 the former providing the basis for the recommended protocol of REPs. Below is a summary of the most recently revised clinical recommendations for REP proposed by the American Association of Endodontists: 67 First appointment (1) Local anaesthesia, dental dam isolation and access. (2) Copious, gentle irrigation with 20 ml 1.5% NaOCl using an irrigation system that minimizes the possibility of extrusion of irrigants into the periapical space. (3) Dry canals with paper points. (4) Place calcium hydroxide or low concentration of triple antibiotic paste. If the triple antibiotic paste is used: (a) consider placing a dentine bonding agent in the pulp chamber [to minimize risk of staining]; and (b) mix 1:1:1 ciprofloxacin: metronidazole:minocycline to a final concentration of 0.1 mg/ml. (5) If triple antibiotic paste is used, ensure that it remains below the CEJ. (6) Place 3 4 mm of a temporary restorative material such as Cavit, IRM, GIC or another temporary material. Dismiss patient for 1 4 weeks Second appointment (1 4 weeks after first visit) (1) Assess response to initial treatment. If there are signs/symptoms of persistent infection, consider additional treatment time with the antimicrobial, or an alternative antimicrobial, intracanal dressing. (2) Anaesthesia with 3% mepivacaine without vasoconstrictor. (3) Rubber dam isolation. (4) Copious, gentle irrigation with 20 ml of 17% EDTA. (5) Dry with paper points. (6) Create bleeding into the root canal system by over-instrumenting (induce by rotating a precurved K-file at 2 mm past the apical foramen with the goal of having the entire canal filled with blood to the level of the CEJ). (7) Stop bleeding at a level that allows for 3 4 mm of restorative material. (8) Place white MTA as the capping material. MTA has been associated with discolouration. Alternatives to MTA (such as resin-modified glass ionomer or bioceramics) should be considered in teeth where there is an aesthetic concern. (9) A3 4 mm layer of GIC is flowed gently over the capping material. Follow-up (1) Clinical and radiographic exam: o No pain, soft tissue swelling or sinus tract (healing is often observed between the first and second appointments). o Resolution of the periapical radiolucency (often observed 6 12 months after treatment). o Increased width of the root walls and length of the root. o Positive pulp sensibility test response (not always present). As can be seen, the REP technique is not a simple one and a clear understanding of each of the clinical steps is imperative. The intention of this review is neither to dismiss nor advocate a particular procedure and this has been the rationale for providing the current 67 REP treatment protocol. However, the clinician should be aware of the pitfalls and disadvantages of a relatively new technique that lacks high levels of evidence and is largely based on case reports. Identified problems with REPs It is important to note that the outcomes of REPs are to date based on case studies alone. These case studies lack the use of a standardised treatment protocol and include a broad range of differences in the aetiology of treated disease, chemo-mechanical debridement regimen, number of visits and intra-canal medicament. 4 Indeed, many of these case studies involve no more than one or two teeth and the lack of consistency as to the aetiology (trauma, caries, dens evaginatus, etc.) makes it extremely difficult to draw any conclusions about the outcomes, as the impact on HERS in partic Australian Dental Association

9 Management of incompletely developed teeth ular varies greatly from one case to another. Case studies are unreliable in determining success and failure outcomes 68 with the Centre for Evidence Based Medicine at Oxford University ranking case studies as the lowest form of evidence-based studies (Level 5). 68 Minocycline (a component in the TAP) and MTA have been identified as possible causes of discolouration of a tooth following an REP and patients should be warned of the possibility of this occurring. In a recent article, of 16 teeth treated without the minocycline component in the TAP (substituted with amoxicillin) were found to have discoloured and the authors concluded that the use of grey and white MTA was the cause. Internal bleaching may be required but this may not be feasible if MTA has been placed within the pulp chamber due to the difficulties associated with its removal. It is interesting to note that as a result of this complication, a technique without the use of the TAP has been suggested. 70 In an editorial, Nair 55 argued that proponents of regenerative endodontics have not yet seen the elephant in the room, namely, that to date there has been no evidence of an acceptable pulp-odontoblastdentine complex in these infected cases, and it is indeed the presence of infection which is precluding that outcome, primarily caused by continued challenges in dealing with residual biofilms in all aspects of endodontics. He states that research should be focused on generative dentistry and likens it to demolishing an old decrepit house and rebuilding it according to its original design, rather than retaining it by carrying out a soft renovation. 55 The creation of the blood clot has also been reported during the second stage to have been met with difficulty. Kahler et al., 69 despite using an anaesthetic without a vasoconstrictor, could not initiate bleeding in some of their cases. They also reported that even if bleeding was initiated, the amount of blood required for clot formation was insubstantial. Another report, where a vasoconstrictor was used, failed to cause bleeding in 4 of 12 teeth. 71 As a result of this possible complication, the use of a plasma-rich plasma (PRP) scaffold has been suggested, 72 where blood is drawn from the patient, red blood cells are removed and thrombin and calcium are added to prepare the PRP. The use of PRP is designed to replicate the functions of a naturally occurring blood clot/scaffold as it contains the following properties: (1) stimulates collagen production; (2) contains growth factors; (3) promotion of vascular ingrowth; and (4) induces cell differentiation. 72 However, the practicalities of the creation and subsequent placement of a PRP scaffold in a clinical dental setting will likely preclude it from being used in most practices. Subsequent to this study, in a pilot study using ferrets, histologic examination has been carried out on the type of tissue formed following blood clot creation and the use of PRP as a scaffold. 59 The authors found, histologically, in both groups an ingrowth of bonelike tissue from the apical region extending to the coronal third of the root. 59 Connective tissue was also identified in the pulp space in association with fibroblasts and blood vessels. Interestingly, the authors concluded that the thickening of the root was essentially due to the presence of bone and cementum rather than dentine. Therefore, if this is the case, the claimed advantage of increased resistance to fracture following a REP comes into question. As previously mentioned, a long-held cited disadvantage associated with apexification has been increased susceptibility to fracture due to cessation of dentine deposition in the cervical one third of the root. As histological studies are continuing to show no evidence of dentine deposition following a REP (especially in the coronal third of the root), one needs to question if there is any difference in the long term with respect to fracture resistance in either treatment scenario. Long-term prospective clinical studies are indicated prior to these claims continuing to be made. Authors of a recent histological study 73 reported that following bone ingrowth into the pulp space (a now known phenomenon following REPs), replacement resorption, as a result of fusion between the bone and the canal wall, was identified due to the absence of the protective qualities of the PDL against resorption. Replacement resorption could therefore be a long-term outcome of REPs. Recent case reports 74 continue to claim evidence of an increase in root length and thickness following a REP. However, the lack of radiographic standardization renders the findings impossible to draw any definitive conclusions other than subjective interpretation (which is consistently reported positively 4 ). Indeed, the case cited 74 presents three radiographic images (preoperative, 6 months and 1 year) with three different angulations. Research is also lacking as to the true long-term impact of these marginal improvements in length and thickness with respect to fracture resistance and tooth survival. There is little doubt REPs have captured the imagination of endodontic researchers and continued investigations into the procedure are to be commended and encouraged. However, the reliance on case studies alone to determine treatment protocols is troublesome and has medico-legal and ethical implications. Additionally, the uncertainty of what is actually being produced in the pulp space following these procedures will hopefully be clarified and that well-designed prospective outcome studies are to be produced Australian Dental Association 103

10 SC Harlamb Equally of concern is that as REPs are reliant on the presence of a scaffold and subsequent cell differentiation in the apical papilla region, the differing impact of disease process in that region needs further clarification. For example, one would expect that following an intrusive luxation injury, cells in the apical region of an immature tooth behave and respond differently to those same cells in a tooth affected by a long-term caries lesion progression or an exposed pulp due to a genetic malformation such as a dens evaginatus where the apical PDL has not been damaged or affected. The authors of a recent review 75 recommended a REP only be considered if the other alternatives (apexification and partial pulpotomy) were not possible, i.e. the procedure should be treated as the option of last resort. Given the lack of long-term outcome studies and as yet incomplete understanding of the biologic responses following initiation of an REP, there is little reason to not support their proposition. SUMMARY An immature permanent tooth which has been subjected to a traumatic episode requires careful clinical and radiographic examination prior to committing it to endodontic treatment. As has been shown, the immature tooth, in a number of trauma scenarios, has a good chance of revascularizing without any clinical intervention. If a necrotic and infected pulp within such teeth has been definitively diagnosed, then endodontic treatment can pose clinical challenges. Although treatment protocols such as apexification techniques have been in existence for many years, the reality of dealing with a structurally weakened tooth persists, with cervical fractures in particular being an ongoing concern. Caution needs to be exercised when so-called regenerative procedures are to be considered. Claims that pulp is being regenerated are simply not supported by many recent histologic findings and, as such, proven therapies such as apexification should still be considered the first treatment of choice. DISCLOSURE The author has no conflicts of interest to declare. REFERENCES 1. Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta percha. A restrospective clinical study. Endod Dent Traumatol 1992;8: Rafter M. Apexification: a review. Dent Traumatol 2005;21: Nygaard-Ostby B. The role of the blood clot in endodontic therapy. An experimental histologic study. Acta Odontol Scand 1961;13: Diogenes A, Henry MA, Teixeira FB, Hargreaves KM. An update on clinical regenerative endodontics. Endod Topics 2013;28: Andreasen J, Ravn JJ. Epidemiology of traumatic dental injuries to primary and permanent teeth in a Danish population sample. Int J Oral Surg 1972;1: Malmgren B, Malmgren O, Andreasen JO. Alveolar bone development after decoronation of ankylosed teeth. Endod Topics 2006;14: Trope M. Treatment of immature teeth with non-vital pulps and apical periodontitis. Endod Topics 2006;14: Soder PO, Otteskog P, Andreasen JO. Effect of drying on viability of periodontal membrane. Scand J Dent Res 1977;85: Filippi A, Pohl Y, von Arx T. Decoronation of an ankylosed tooth for preservation of alveolar bone prior to implant placement. Dent Traumatol 2001;2: Malmgren B, Cvek M, Lundberg M, Frykholm A. Surgical treatment of ankylosed and infrapositioned reimplanted incisors in adolescents. Scand J Dent Res 1984;92: International Association of Dental Traumatology. IADT guidelines for the management of traumatic dental injuries. Dent Traumatol 2012;28: Andreasen JO, Borum MK, Andreasen FM. Replantation of 400 avulsed permanent incisors. 3. Factors related to tooth growth. Endod Dent Traumatol 1995;11: Kling M, Cvek M, Mejare I. Rate and predictability of pulp revascularisation in therapeutically reimplanted permanent incisors. Endod Dent Traumatol 1986;2: Trope M. Clinical management of the avulsed tooth: present strategies and future directions. Dent Traumatol 2002;18: International Association of Dental Traumatology. Dental Trauma Guide: URL: org/permanent_avulsion_treatment.aspx. Accessed June Fulling HJ, Andreasen JO. Influence of maturation status and tooth type of permanent teeth upon electrometric and thermal pulp testing procedures. Scand J Dent Res 1976;84: Andreasen JO. Etiology and pathogenesis of traumatic dental injuries. A clinical study of 1298 cases. Scand J Dent Res 1970;78: Andreasen FM, Pedersen BV. Prognosis of luxated permanent teeth the development of pulp necrosis. Endod Dent Traumatol 1985;1: Andreasen FM, Zhijie Y, Thomsen BL. Relationship between pulp dimensions and development of pulp necrosis after luxation injuries in the permanent dentition. Endod Dent Traumatol 1986;2: Andreasen FM. Histological and bacteriological study of pulps extirpated after luxation injuries. Endod Dent Traumatol 1988;4: Andreasen JO, Andreasen FM. Intrusive Luxation. In: Andreasen JO, Andreasen FM, Andersson L, eds. Textbook and Color Atlas of Traumatic Injuries to the Teeth. 4th edn. Oxford: Blackwell Munksgaard, 2007: Andreasen JO, Borum MK, Jacobsen HL, Andreasen FM. Replantation of 400 avulsed permanent incisors. 2. Factors related to pulpal healing. Endod Dent Traumatol 1995;11: Harlamb SC, Messer HH. Endodontic management of a rare combination (intrusion and avulsion) of dental trauma. Endod Dent Traumatol 1997;1: Andreasen JO, Bakland LK, Andreasen FM. Traumatic intrusion of permanent teeth. Part 3. A clinical study of the effect of treatment variables such as treatment delay, method of repositioning, type of splint, length of splinting and antibiotics on 140 teeth. Dent Traumatol 2006;22: Australian Dental Association

11 Management of incompletely developed teeth 25. Andreasen JO, Bakland LK, Andreasen FM. Traumatic injuries of permanent teeth. Part 2. A clinical study of the effect of preinjury and injury factors, such as sex, age, stage of root development, tooth location and extent of injury including number of intruded teeth on 140 intruded permanent teeth. Dent Traumatol 2006;22: Andreasen JO, Bakland LK, Andreasen FM, Matras RC. Traumatic intrusion of permanent teeth. Parts 1 3. Dent Traumatol 2006;22: Cvek M. Endodontic management and the use of calcium hydroxide in traumatised permanent teeth. In: Andreasen JO, Andreasen FM, Andersson L, eds. Textbook and Color Atlas of Traumatic Injuries to the Teeth. 4th edn. Oxford: Blackwell Munsgaard, 2007: Cvek M. A clinical report on partial pulpotomy and capping with calcium hydroxide in permanent incisors with complicated crown fractures. J Endod 1978;4: Cvek M, Cleaton-Jones P, Austen J, Andreasen JO. Pulp reactions to exposure after experimental crown fractures or grinding in adult monkeys. J Endod 1982;8: Torabinejad M, Rastegar AF, Kettering JD, Pitt Ford TR. Bacterial leakage of MTA as a root end filling material. J Endod 1995;21: American Association of Endodontists. Glossary of Endodontic Terms. 8th edn. Chicago: AAE, Hermann BW. Dentinobleration der Wurzelkanale nach der Behandlung mit Kalcium. Zahnarzt Rundscau. 1930;39: Bystrom A, Claesson R, Sundqvist G. The antibacterial effect of CMCP, camphorated phenol and CH in the treatment of infected root canals. Endod Traumatol 1985;1: Turkun M, Gengiz T. The effects of NaOCl and CH on tissue dissolution and root canal cleanliness. Int Endod J 1997;30: Steiner JC, Van Hassel HJ. Experimental root apexification in primates. Oral Surg 1971;31: Frank AL. Therapy for the divergent pulpless tooth by continued apical formation. J Am Dent Assoc 1966;72: Kaiser HJ. Management of wide open apex canals with calcium hydroxide. 21st Annual Meeting of the American Association of Endodontists. Washington DC, Heithersay GS. Stimulation of root formation in incompletely developed pulpless teeth. Oral Surg 1970;29: Feiglin B. Differences in apex formation during apexification with calcium hydroxide paste. Endod Dent Traumatol 1985;1: Naoum HJ, Chandler NP. Temporization in endodontics. Int Endod J 2002;35: Abbott PV. Apexification with calcium hydroxide when should the dressing be changed? Aust Endod J 1998;24: Chawla HS. Apical closure in a nonvital permanent tooth using one calcium hydroxide dressing. J Dent Child 1986;53: Ballesio I, Marchetti E, Mummolo S, Marzo G. Radiographic appearance of apical closure in apexification: follow up after 7 13 years. Eur J Paediatr Dent 2006;7: Cvek M. Treatment of non-vital permanent incisors with calcium hydroxide. I. Follow-up of periapical repair and apical closure of immature roots. Odonotol Revy 1972;23: Brand AA. The child dental patient: Part 1 the nature and prevalence of children s dental fears. SADJ 1999;54: Torabinejad M, Abu-Tahun I. Management of teeth with necrotic pulps and open apices. Endod Topics 2012;23: Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a root canal dressing may increase root fracture. Dent Traumatol 2002;18: Torabinejad M, Chivian N. Clinical applications of mineral trioxide aggregate. J Endod 1999;25: Torabinejad M, Hong CU, McDonald F, Pitt Ford TR. Physical and chemical properties of a new root end filling material. J Endod 1995;21: Witherspoon DE, Small JC, Regan JD, Nunn M. Retrospective analysis of open apex teeth obturated with mineral trioxide aggregate. J Endod 2008;34: Friedland M, Rosado R. MTA solubility: a long term study. J Endod 2005;31: Desai S, Chandler NP. The restoration of permanent immature anterior teeth, root filled using mineral trioxide aggregate: a review. J Dent 2009;37: Huang GJ. A paradigm shift in endodontic management of immature teeth: conservation of stem cells for regeneration. J Dent 2008;36: Spangberg LSW. The Emperor s new cloth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108: Nair PNR. Endodontic biofilm, technology and pulpal regenerative therapy: where do we go from here? Int Endod J 2014;47: Trope M. Regenerative potential of dental pulp. J Endod 2008;34:S Patel R, Cohenca N. Maturogenesis of a cariously exposed immature permanent tooth using MTA for direct pulp capping: a case report. Dent Traumatol 2006;22: Lenzi R, Trope M. Revitalization procedures in two traumatized incisors with different biological outcomes. J Endod 2012;38: Torabinejad M, Faras H, Corr R, Wright KR, Shabahang S. Histologic examinations of teeth treated with two scaffolds: a pilot animal examination. J Endod 2014;40: Schmalz G, Smith AJ. Pulp development, repair and regeneration: challenges of the transition from traditional dentistry to biologically based therapies. J Endod 2014;40:S Sonoyama W, Liu Y, Fang D, et al. Mesenchymal stem cellmediated functional tooth regeneration in swine. PLoS One 2006;1:e Law AS. Considerations for regeneration procedures. J Endod 2013;39:S Hoshino E, Kurihara-Ando N, Sato I, et al. In vitro antibacterial susceptibility of bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline. Int Endod J 1996;29: Wigler R, Kaufman AY, Lin S, Steinbock N, Hazan-Molina H, Torneck CD. Revascularisation: a treatment for permanent teeth with necrotic pulp and incomplete root development. J Endod 2013;39: Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dent Traumatol 2001;17: Banchs F, Trope M. Revascularisation of immature permanent teeth with apical periodontitis: new treatment protocol? J Endod 2004;30: American Association of Endodontists. AAE Clinical Considerations for a Regenerative Procedure. Available at: currentregenerativeendodonticconsiderations.pdf. Accessed June Torabinejad M, Kutsenko D, Machnick TK, Ismail A, Newton CW. Levels of evidence for the outcome of nonsurgical endodontic treatment. J Endod 2005;9: Australian Dental Association 105