|Year : 2020 | Volume
| Issue : 2 | Page : 137-144
Awareness, attitude, and practice of regenerative endodontic procedures among clinicians from different dental specialties
Mohamed Jamal1, Summayah Khawaja1, Sami Chogle2
1 Department of Endodontics, Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
2 Department of Endodontics, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA, USA
|Date of Submission||23-Aug-2019|
|Date of Decision||21-Sep-2019|
|Date of Acceptance||27-Sep-2019|
|Date of Web Publication||23-Apr-2020|
Dr. Mohamed Jamal
Department of Endodontics, Hamdan Bin Mohamed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Building 14, Dubai Health Care City, Dubai
United Arab Emirates
Source of Support: None, Conflict of Interest: None
Introduction: This study assessed the opinions on and practice of regenerative endodontic procedures (REPs) among clinicians from different dental specialties.
Materials and Methods: After the Institutional Review Board approval, 205 clinicians participated in a web-based survey and were asked about their educational level, professional status, opinion toward REPs, and preferred technique when performing REPs.
Results: Although approximately 65% of participants were unsure or did not believe that there is enough evidence to support REPs, 78.2% believed that REPs are a better treatment option than apexification and 70.5% that they could be a future alternative to osseointegrated implants. The results also revealed variability in the preferred techniques to perform REPs, with 40.4% preferring the use of a mixture of antibiotics to disinfect the root canal space, whereas 20.2% preferred calcium hydroxide. Almost 66% were using ≥1 mg/mL of each antibiotic in the mixture, whereas 44.6% were using 0.1 mg/mL. Approximately 40% of participants used techniques that differ from the American Association of Endodontists' clinical considerations for REPs. Interestingly, attending a continuing dental education course (CDE) significantly reduced the participants' uncertainty toward REPs and increased their willingness to perform it themselves (P < 0.001).
Conclusions: This survey revealed a positive attitude toward and general acceptance of REPs by dentists. It also showed considerable variability in techniques used to perform REPs. Conducting more CDE may increase the awareness of REPs among different dental specialties and reducing variability in techniques.
Keywords: Apexification, regenerative endodontics, stem cells, tissue engineering
|How to cite this article:|
Jamal M, Khawaja S, Chogle S. Awareness, attitude, and practice of regenerative endodontic procedures among clinicians from different dental specialties. Saudi Endod J 2020;10:137-44
|How to cite this URL:|
Jamal M, Khawaja S, Chogle S. Awareness, attitude, and practice of regenerative endodontic procedures among clinicians from different dental specialties. Saudi Endod J [serial online] 2020 [cited 2020 Jun 4];10:137-44. Available from: http://www.saudiendodj.com/text.asp?2020/10/2/137/283135
| Introduction|| |
Endodontic treatment of immature permanent teeth with pulp necrosis presents quite a challenge to dentists. Pulp necrosis in immature teeth due to caries or trauma eventually leads to incomplete root development, resulting in roots with thin dentinal walls and an open apex. Management of such teeth with conventional cleaning, shaping, and obturation methods is challenging due to the thin walls and lack of an apical barrier.
One of the common techniques for the treatment of immature permanent teeth with necrotic pulp is apexification. This uses calcium hydroxide (Ca[OH]2) to induce a hard-tissue apical barrier. Ca (OH)2 apexification has been used in the past few decades with a reported success rate of 74%–95%., The idea of using Ca(OH)2 for the induction of a calcified apical barrier was first proposed by Kaiser in 1964. Despite the long history of Ca(OH)2 apexification and its reported success rate, this technique has certain drawbacks. Multiple appointments, long follow-up, inability to promote root development, and a high incidence of root fracture, are some of the disadvantages. Several research publications and case reports have proposed using mineral trioxide aggregate (MTA) to induce an apical barrier, as a promising alternative to Ca (OH)2 apexification.,,, MTA apexification gained wide popularity due to its superior apical seal induction, and the fact that it heals apical periodontitis and requires less visits than Ca (OH)2 apexification. The main disadvantages of MTA are difficult manipulation, technique sensitivity, and high cost of the material.
Although apexification techniques were able to induce an apical barrier and facilitate obturation, none promote root development and dentin thickening of canal walls; therefore, the possibility of root fracture of these teeth still exists.
To overcome these drawbacks, interest has shifted to biologically based techniques. Progress in dental stem cell research, disinfection protocols, and biomaterial science led to the development of regenerative endodontic procedures (REPs).
Until now, hundreds of research articles and case reports have been published on REPs, reporting variable clinical outcomes, resolution of apical pathosis, continued root development, increased thickness of canal wall dentin, and in few cases, claims of regaining the pulp vitality., The main objective of REPs is to regenerate and re-establish the functionality of the pulp–dentin complex. Thus, REPs are considered a promising alternative to manage the necrotic immature permanent teeth.
In 2013, the American Association of Endodontists (AAE) issued a position statement regarding regenerative endodontics stating that it is within the scope of practice of endodontics. In 2014, it introduced revisions to include in-depth training on REPs in postgraduate endodontic programs. Furthermore, the AAE has developed an evidence-based protocol for REPS, “Clinical Considerations for a Regenerative Procedure,” which is regularly updated.
With the increasing evidence and successful outcomes of REPs, a greater number of endodontists are using them in their clinical practice for the treatment of necrotic immature teeth.,, However, as is evident in the literature and published case reports, different protocols are being used for REPs.,,, Moreover, there are no clear data on the awareness of and beliefs about REPs among clinicians from different specialties and the clinical protocol they employ in their clinical practice. Hence, this survey was designed and conducted to assess the knowledge, awareness, attitudes, and practice of REPs among clinicians from different dental specialties.
| Materials and Methods|| |
After obtaining Boston University Medical Center Institutional Review Board approval (#H-33,404), a total of 1751 questionnaires were distributed through a web-based survey (Google forms). Distribution was done anonymously using the Boston University database of current dental students, faculty members, and alumni from all specialties, including general dentists, endodontists, periodontists, pedodontists, prosthodontist, oral surgeons, and orthodontists.
The questionnaire was divided into three parts: Part A consisted of four questions focused on sociodemographic information and dentists' professional status; Part B (Q5–10) asked questions about the dentist's opinions, beliefs, and attitudes regarding the use of REPs; and Part C (Q11–17) focused on the clinical protocol and was completed only by those who indicated that they perform REPs themselves (Q10). [Table 1] provides a full list of the questions and responses. Microsoft Excel was used for data entry. The analysis was performed using the IBM SPSS Statistics for Windows (IBM Corp Armonk, NY), version 24.0. The Chi-square test was used for the analysis of the descriptive statistics.
| Results|| |
Profile of participants
A total of 205 completed questionnaires were received, giving a response rate of 11.7%. Of the 205 participants, 97 (47.3%) were endodontists, 26 (12.7%) periodontists, 26 (12.7%) dental students, 19 (9.3%) general dentists, 14 (6.8%) prosthodontists, 13 (6.3%) orthodontists, 7 (3.4%) oral surgeons, and 3 (1.5%) pedodontists.
Around half of the participants (51.2%) had been practicing dentistry for more than 10 years. More than half of the participants (58.2%) were in private practice. A continuing dental education course (CDE) on stem cells and regeneration had been attended by 52.7%, and almost 69.4% of attendees were endodontists.
Opinions and beliefs about regenerative endodontic procedures
The second part of the survey assessed the opinions and beliefs of the participants about REPs. Approximately one-third of the participants (34.6%) believed that there is enough evidence to support the use of REPs. Of all the specialties, the most endodontists (51%) believed this. However, less than one-third of the participants (27.3%) believed that functional pulp tissue could be generated by REPs, and 38.1% of these were endodontists.
When asked their opinion of REPs in comparison to apexification, more than two-thirds of participants (78.2%) preferred REPs, and 52.5% of these were endodontists. Most participants (93.6%) believed that an entire tooth could be regenerated in the laboratory in 0–30 years. Most participants (70.5%) believed that implanting a regenerated tooth will be a better option than osseointegrated implants; of these, 54.6% were endodontists, 14.2% dental students, 9.2% periodontists, 8.5% general dentists, 5.7% orthodontist, 3.5% prosthodontists, 2.8% oral surgeons, and 1.4% pedodontists.
Regarding performing REPs, 49.3% of the participants were willing to do so themselves, while 50.7% would prefer to refer these procedures to an endodontist. Overall, most endodontists (80.7%) were willing to perform REPs themselves, followed by general dentists (6.9%), dental students (6.9%), periodontists (3%), pedodontists (1%), oral surgeons (1%), and prosthodontists (1%). None of the orthodontists chose to perform REPs themselves.
Clinical practice of regenerative endodontic procedures
The third part of the survey assessed the technical steps and protocols used to perform REPs. More than two-thirds of the participants (72%) were comfortable performing REPs on a tooth with necrotic pulp and an immature apex. Most (83.3%) of the endodontists, 5.6% of the dental students, 4.2% of the general dentists, 1.4% of pedodontists, 1.4% of prosthodontists, and 4.2% of periodontists preferred to do REPs on a tooth with necrotic pulp and immature apex. More than half of the participants (63.8%) stated that two or more visits are required to perform REPs, most of these respondents (90%) being endodontists.
To achieve disinfection of the root canal system, 40.4% of the participants were using a mixture of antibiotics, 20.2% used Ca (OH)2, and 39.4% used both. In the endodontist subgroup, 38.2% opted for the antibiotic mix, 22.4% for Ca(OH)2, and 39.5% for both.
More than two-thirds of the participants (75.3%) preferred to use a 1:1:1 ratio of ciprofloxacin, metronidazole, and minocycline for the antibiotic mixture, with 82% of endodontists using this ratio.
When it comes to the concentration of each antibiotic in the antibiotic mixture, 44.6% of the participants would use 0.1 mg/mL, and most of these (87.9%) were endodontists. A further 48.6% would use 1 mg/mL and 6.8% would use 10 mg/mL. In the endodontist subgroup, 49.2% used 0.1 mg/mL, 49.2% used 1 mg/mL, and 1.7% used 10 mg/mL.
When asked how they would deliver stem cells to the root canal system, more than half (55.1%) of the participants stated that they would do so by initiating bleeding from the periapical area, 7.9% by orthograde delivery through a syringe, while 37.1% said they would use both techniques. Most (93.9%) of those who used initiation of bleeding from the periapical area were endodontists.
The last question of the survey was about sources participants used to develop their protocol for REPs. Approximately 20% stated that they relied solely on the AAE's clinica considerations, whereas 42.1% combined the AAE's clinical considerations with published literature, CDE courses and colleauges' advise. Others only used CDE courses (20%) or published literature (12%). Among the endodontist subgroup, most (82.1%) were following the AAE's clinical considerations for REPs.
Correlation among different variables
Attending a CDE course on REPs significantly reduced uncertainty among participants about the availability of enough evidence to support REPs (P < 0.001) [Figure 1]a. Furthermore, attending a CDE significantly increased the percentage of participants who preferred REPs over apexification (P < 0.001) and increased the percentage of participants performing REPs by 33% (P < 0.001) [Figure 1]b. However, attending a CDE had no significant influence on participants' belief in regenerating a tooth in a laboratory or their choice between a dental implant or implanting a regenerated tooth. Clinically, attending a CDE significantly influenced the participants' case selection [Figure 1]c and stem cell delivery for REPs (P < 0.05).
|Figure 1: Bar chart indicating the correlation of attending a continuous dental education with (a) the availability of enough evidence supporting regenerative endodontic procedures, (b) the willingness to perform regenerative endodontic procedures or referring it to an endodontist, and (c) case selection|
Click here to view
Participants' specialty significantly influenced their beliefs about REPs (P < 0.05). Most of the endodontists keenly believed in REPs and answered in favor on all the related beliefs, compared to dentists from other specialties (P < 0.05).
| Discussion|| |
The survey yielded a very positive response regarding REPs among the participants who were from different dental specialties, including dental students, with 47.3% being endodontists.
Just over half of the participants (52.6%) have attended a CDE on stem cells and regeneration, which is very encouraging and reflects the increasing interest in this rapidly advancing field. Endodontists were the largest subgroup (70%) to attend CDEs, possibly because REPs are part of the endodontic training program, and most necrotic immature teeth are treated by them.
Our results indicate that more than two-thirds of the participants (78.2%) believed that REPs are a better treatment option than apexification. This preference could be attributed to recent studies on REPs, which claim that REPs provide a better outcome than apexification in terms of increased root thickness and root length.
Moreover, a study on survival outcome of immature treated teeth has documented a higher (100%) survival rate for teeth treated with REPs, compared to 95% and 77.2% for MTA and Ca (OH)2 apexification, respectively.
Various published studies have used different experimental models to regenerate dentin, pulp, and periodontal ligament-like tissues., In 2004, Ohazama et al. succeeded in developing rootless tooth-like structures in rodents. Young et al. succeeded in forming dentin and enamel-like structures by reimplanting bioengineered tooth and bone implants in adult rats. The influence of this ongoing progress in dental tissue bioengineering is evident in our survey, where the vast majority (93.6%) of participants believed in the possibility of an entire tooth being regenerated in future. These findings complement those of surveys by Manguno et al. and Epelman et al.,,
More than 70.5% of participants agreed that implanting a regenerated tooth is a better approach than osseointegrated titanium implants. Despite the long history and success of implants, the lack of a stress distribution function of the periodontal ligament means that these are not ideal replacements. Moreover, this shows an exciting shift toward regenerative dentistry over the traditional treatment options and increasing interest of dentists in exploring biologically based techniques for the replacement of missing teeth. This positive response could be attributed to the case reports, increased number of published studies on regenerative endodontics, and progress in research on dental tissue engineering.,,,
As far as the clinical practice of REPs is concerned, approximately half of the participants (49.3%) were willing to perform it themselves, whereas 50.7% opted to refer the procedure to an endodontist. This could be due to the fact that REPs fall within the scope of endodontics. Although only 19.9% of dentists from other specialties were performing REPs, this reflects an encouraging trend and interest of dentists from all specialties in adopting this promising technique. However, it also sheds light on the lack of clinical knowledge and training on REPs in other dental specialties in general.
In this study, more than two-thirds of the participants (72%) were more comfortable doing REPs on necrotic immature teeth. This finding is in accordance with most published literature, where most REP cases with successful outcomes were performed on necrotic immature teeth.,, Furthermore, current evidence and research data on REPs on mature teeth show the healing of periapical lesions; however, they do not recover tooth vitality. Therefore, in mature teeth, REPs do not necessarily provide any significant advantage over current conventional endodontic treatment modalities which have a high success rate (86%–98%).,
Around 40.4% of participants were using triple antibiotics paste (TAP) for disinfection, whereas 20.2% preferred to use Ca(OH)2, and 39.4% used both. These results complement the findings of a review by Diogenes et al. on published cases and studies on REPs, where 51% were disinfected by TAP and 37% used Ca(OH)2 for disinfection. The successful use of TAP in REPs and its antibacterial effect against the mixed population of microbes in the canal have been proven by different studies., Several studies have supported the use of Ca(OH)2 in REPs for its effective antibacterial properties and positive effect on the survival and proliferation of stem cells of the apical papilla (SCAP).,, The use of both Ca(OH)2 and TAP for disinfection is recommended in the AAE's clinical considerations.
According to the findings of this survey, 44.6% of participants would use 0.1 mg/mL of the antibiotic mixture, whereas 48.6% would use 1 mg/mL and 6.8% would use 10 mg/mL. Higher concentrations of TAP have a toxic effect on the survival of SCAP, whereas according to Ruparel et al., TAP in lower concentrations of 0.01–0.1 mg/mL has no such toxic effect, while concentrations of 1–6 mg/mL reduced the SCAP survival rate by 50%., However, Labban et al. stated that TAP in a concentration of 2 mg/mL has no toxic effect on dental pulp stem cells. Similar findings were reported by Althumairy et al. with TAP at 1 mg/mL not affecting the survival of SCAP. These differences in the safest nontoxic concentration of TAP could be due to the different methodologies used in these studies.
For the delivery of stem cells, around 55.1% of participants evoked bleeding from the periapical area, which is the most established and used method.,
This survey shows a wide variation in the clinical protocol used to perform REPs. This finding is similar to Diogenes et al.'s findings in a review of 34 publications (2001–2013) on REPs, which revealed lack of a standardized treatment protocol such as the number of visits and disinfection routine. Bukhari et al. and Almutairi et al. have also emphasized this aspect., Such variation in protocols can pose a challenge in determining the factors that affect the clinical success of REPs and also affect the possibility of conducting a well-designed meta-analysis, as reported by Almutairi et al.
Another possible factor in the variability in REPs protocols is the sources dentists used to develop protocols for their practice. Our results showed that 62% used the AAE's published clinical considerations, either alone or in combination with other resources, while 38% based their protocol on information obtained from the published literature, CDE courses, or both. The effect of relying on different resources for developing the clinical protocol for REPs is made evident by the differences in techniques employed by the participants in this survey [Figure 2].
|Figure 2: Bar chart showing participants' preferred techniques and their agreement with the American Association of Endodontists “Clinical Consideration for Regenerative Endodontic Procedures”|
Click here to view
Furthermore, variations in REPs protocols provide important insight into the lack of knowledge and clinical training on REPs among different dental specialties. Our results indicate that attending CDE significantly reduced uncertainty among participating dentists regarding the availability of enough evidence to support REPs, choosing between REPs and apexification, and case selection. Therefore, conducting more CDE courses for dentists from different dental specialties that promote an evidence-based standardized REPs protocol can be an effective strategy to reduce variations in REPs protocols.
| Conclusions|| |
The data from this survey revealed a positive attitude and general acceptance of dentists toward REPs. Moreover, there is a need to develop and promote a standardized REPs protocol. The lack of a standardized REPs protocol for practice can affect our ability to conduct strong outcomes studies, such as meta-analyses and systematic reviews.
Furthermore, conducting more CDE courses on REPs can be a possible strategy to reduce the uncertainty toward REPs, encourage dentists from different dental specialties to consider REPs and to use them when indicated, and to reduce variability in the REPs protocols used by promoting a standardized protocol.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Trope M. Treatment of the immature tooth with a non-vital pulp and apical periodontitis. Dent Clin North Am 2010;54:313-24.
Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha. A retrospective clinical study. Endod Dent Traumatol 1992;8:45-55.
Heithersay GS. Stimulation of root formation in incompletely developed pulpless teeth. Oral Surg Oral Med Oral Pathol 1970;29:620-30.
Kaiser HJ. Management of wide open apex canals with calcium hydroxide. Presented at the 21st
Annual Meeting of the American Association of Endodontists, Washington DC, 1964.
Conde MC, Chisini LA, Sarkis-Onofre R, Schuch HS, Nör JE, Demarco FF. A scoping review of root canal revascularization: Relevant aspects for clinical success and tissue formation. Int Endod J 2017;50:860-74.
Albadri S, Chau YS, Jarad F. The use of mineral trioxide aggregate to achieve root end closure: Three case reports. Dent Traumatol 2013;29:469-73.
Giuliani V, Baccetti T, Pace R, Pagavino G. The use of MTA in teeth with necrotic pulps and open apices. Dent Traumatol 2002;18:217-21.
Simon S, Rilliard F, Berdal A, Machtou P. The use of mineral trioxide aggregate in one-visit apexification treatment: A prospective study. Int Endod J 2007;40:186-97.
Witherspoon DE, Small JC, Regan JD, Nunn M. Retrospective analysis of open apex teeth obturated with mineral trioxide aggregate. J Endod 2008;34:1171-6.
Economides N, Pantelidou O, Kokkas A, Tziafas D. Short-term periradicular tissue response to Mineral Trioxide Aggregate (MTA) as root-end filling material. Int Endod J 2003;36:44-8.
Shabahang S, Torabinejad M, Boyne PP, Abedi H, McMillan P. A comparative study of root-end induction using osteogenic protein-1, calcium hydroxide, and mineral trioxide aggregate in dogs. J Endod 1999;25:1-5.
Chhabra N, Singbal KP, Kamat S. Successful apexification with resolution of the periapical lesion using mineral trioxide aggregate and demineralized freeze-dried bone allograft. J Conserv Dent 2010;13:106-9.
] [Full text]
Damle SG, Bhattal H, Loomba A. Apexification of anterior teeth: A comparative evaluation of mineral trioxide aggregate and calcium hydroxide paste. J Clin Pediatr Dent 2012;36:263-8.
Bose R, Nummikoski P, Hargreaves K. A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root canal systems treated with regenerative endodontic procedures. J Endod 2009;35:1343-9.
Miller EK, Lee JY, Tawil PZ, Teixeira FB, Vann WF Jr. Emerging therapies for the management of traumatized immature permanent incisors. Pediatr Dent 2012;34:66-9.
Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB. Challenges in regenerative endodontics: A case series. J Endod 2010;36:536-41.
Sharma S, Mittal N. A comparative evaluation of natural and artificial scaffolds in regenerative endodontics: A clinical study. Saudi Endod J 2016;6:9-15. [Full text]
AAE Position Statement. Scope of endodontics: Regenerative endodontics. J Endod 2013;39:561-3.
Lee JY, Kersten DD, Mines P, Beltran TA. Regenerative endodontic procedures among endodontists: A Web-based survey. J Endod 2018;44:250-5.
Manguno C, Murray PE, Howard C, Madras J, Mangan S, Namerow KN. A survey of dental residents' expectations for regenerative endodontics. J Endod 2012;38:137-43.
Al Qahtani SS, Aziz S, Al Garni, Alaenazi MS. What opinions do Saudi endodontic residents hold about regenerative endodontics? Saudi Endod J 2019;9:1-7.
Bukhari S, Kohli MR, Setzer F, Karabucak B. Outcome of revascularization procedure: A retrospective case series. J Endod 2016;42:1752-9.
Almutairi W, Yassen GH, Aminoshariae A, Williams KA, Mickel A. Regenerative endodontics: A systematic analysis of the failed cases. J Endod 2019;45:567-77.
Diogenes A, Henry MA, Teixeira FB, Hargreaves KM. An update on clinical regenerative endodontics. Endod Top 2013;28:2-3.
Jeeruphan T, Jantarat J, Yanpiset K, Suwannapan L, Khewsawai P, Hargreaves KM. Mahidol study 1: Comparison of radiographic and survival outcomes of immature teeth treated with either regenerative endodontic or apexification methods: A retrospective study. J Endod 2012;38:1330-6.
Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, et al.
Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 2008;34:962-9.
Wang J, Liu X, Jin X, Ma H, Hu J, Ni L, et al.
The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly (L-lactic acid) scaffoldsin vitro
and in vivo
. Acta Biomater 2010;6:3856-63.
Ohazama A, Modino SA, Miletich I, Sharpe PT. Stem-cell-based tissue engineering of murine teeth. J Dent Res 2004;83:518-22.
Young CS, Abukawa H, Asrican R, Ravens M, Troulis MJ, Kaban LB, et al.
Tissue-engineered hybrid tooth and bone. Tissue Eng 2005;11:1599-610.
Epelman I, Murray PE, Garcia-Godoy F, Kuttler S, Namerow KN. A practitioner survey of opinions toward regenerative endodontics. J Endod 2009;35:1204-10.
Ferreira CF, Magini RS, Sharpe PT. Biological tooth replacement and repair. J Oral Rehabil 2007;34:933-9.
Wigler R, Kaufman AY, Lin S, Steinbock N, Hazan-Molina H, Torneck CD. Revascularization: A treatment for permanent teeth with necrotic pulp and incomplete root development. J Endod 2013;39:319-26.
Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dent Traumatol 2001;17:185-7.
Nosrat A, Seifi A, Asgary S. Regenerative endodontic treatment (revascularization) for necrotic immature permanent molars: A review and report of two cases with a new biomaterial. J Endod 2011;37:562-7.
Saoud TM, Zaazou A, Nabil A, Moussa S, Lin LM, Gibbs JL. Clinical and radiographic outcomes of traumatized immature permanent necrotic teeth after revascularization/revitalization therapy. J Endod 2014;40:1946-52.
Friedman S, Mor C. The success of endodontic therapy – Healing and functionality. J Calif Dent Assoc 2004;32:493-503.
Ng YL, Mann V, Rahbaran S, Lewsey J, Gulabivala K. Outcome of primary root canal treatment: Systematic review of the literature – Part 2. Influence of clinical factors. Int Endod J 2008;41:6-31.
Sato I, Ando-Kurihara N, Kota K, Iwaku M, Hoshino E. Sterilization of infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ
. Int Endod J 1996;29:118-24.
Windley W 3rd
, Teixeira F, Levin L, Sigurdsson A, Trope M. Disinfection of immature teeth with a triple antibiotic paste. J Endod 2005;31:439-43.
Althumairy RI, Teixeira FB, Diogenes A. Effect of dentin conditioning with intracanal medicaments on survival of stem cells of apical papilla. J Endod 2014;40:521-5.
Ruparel NB, Teixeira FB, Ferraz CC, Diogenes A. Direct effect of intracanal medicaments on survival of stem cells of the apical papilla. J Endod 2012;38:1372-5.
Arruda MEF, Neves MAS, Diogenes A, Mdala I, Guilherme BPS, Siqueira JF Jr., et al.
Infection control in teeth with apical periodontitis using a triple antibiotic solution or calcium hydroxide with chlorhexidine: A randomized clinical trial. J Endod 2018;44:1474-9.
Labban N, Yassen GH, Windsor LJ, Platt JA. The direct cytotoxic effects of medicaments used in endodontic regeneration on human dental pulp cells. Dent Traumatol 2014;30:429-34.
Trope M. Regenerative potential of dental pulp. Pediatr Dent 2008;30:206-10.
[Figure 1], [Figure 2]