|Year : 2014 | Volume
| Issue : 3 | Page : 186-189
Regenerative endodontics: Changes, chances, and challenges of revascularization in pediatric dentistry
Mamta Dali1, Laleet Rajbanshi2
1 Department of Pedodontics and Preventive Dentistry, BPKIHS, Dharan, Nepal
2 Department of Anesthesiology and Critical Care, Nobel Medical College and Teaching Hospital, Biratnagar, Nepal
|Date of Web Publication||14-Aug-2014|
Department of Pedodontics and Preventive Dentistry, BPKIHS, Dharan
Source of Support: None, Conflict of Interest: None
Pulp vitality is extremely important for the tooth viability, since it provides nutrition and acts as biosensor to detect pathogenic stimuli. Treatment of the young permanent tooth with a necrotic root canal system and an incompletely developed root is very difficult. Few acceptable results have been achieved through apexification, but use of long-term calcium hydroxide might alter the mechanical properties of dentin. Regenerative endodontic procedures aim at the regeneration of pulp and dentin of the injured teeth. The present article reviews the recent approach of pulp revascularization and provides an overview of its methods with possible future potential of regenerating pulp as a routine dental procedure in pediatric dentistry.
Keywords: Immature, pulp, regenerative endodontics, revascularization, stem cells
|How to cite this article:|
Dali M, Rajbanshi L. Regenerative endodontics: Changes, chances, and challenges of revascularization in pediatric dentistry. SRM J Res Dent Sci 2014;5:186-9
|How to cite this URL:|
Dali M, Rajbanshi L. Regenerative endodontics: Changes, chances, and challenges of revascularization in pediatric dentistry. SRM J Res Dent Sci [serial online] 2014 [cited 2022 May 16];5:186-9. Available from: https://www.srmjrds.in/text.asp?2014/5/3/186/138743
| Introduction|| |
Regenerative endodontics (revascularization/pulpal regeneration) is one of the most exciting new developments in endodontics. The current (2012) American Association of Endodontists defines regenerative endodontics as "biologically-based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as cells of the pulp-dentin complex." 
The origin of biologically compatible regenerative endodontic procedures that allow revival of damaged dentin and root structures, including the cells of pulp-dentin complex dates back to around 1952, when Hermann first reported the application of calcium hydroxide (Ca(OH) 2 ) in vital pulp amputation. 
Until date, its application has been limited to the patients between the age group of 8 and 16 years  and in teeth with minimal periapical pathology. However, the scope of this procedure is changing with the growing evidence of persistence of self-maintained mesenchymal stem cells (MSCs) in adults  and the advent of superior scaffolds like platelet-rich plasma and platelet-rich fibrin that delivers enhanced concoction of growth factors. In addition, the presence of inflamed periapical progenitor cells,  infection survived stem cells from the apical papilla (SCAP)  in teeth with large periapical pathology, may further widen its horizon.
Pulpal necrosis in an immature tooth with an open apex can have devastating consequences for patients and presents a distinctive challenge for the dentist. Though root canal revascularization through blood clotting has become a new norm in regenerative endodontic practice with successful clinical results reported, conventional techniques such as partial pulpotomy, apexification, and apexogenesis are not yet obsolete, and clinicians have to rely on these traditional procedures or the use of apical barriers to treat immature teeth with pulpal necrosis.  Apexification with Ca(OH) 2 has several disadvantages. It requires multiple visits during a long period of time (6-24 months; average, 1 year-7 months), it depends on the parents commitment to ensure the child's dental visits are kept, the barrier formed is often porous and not continuous or compact and also it undermines the mechanical strength of dentin because of a prolonged exposure to Ca(OH) 2 . 
These drawbacks led to the use of mineral trioxide aggregate (MTA) by Torabinejad and Chivian, an alternative to Ca(OH) 2 apexification, where they suggested of cleaning the root canal and sealing the open apex with MTA in 1 or 2 visits could minimize the risk of root canal overfilling and promote apical repair. 
However, clinical experience on the outcome of apexified teeth with thin and weak roots after successful treatment showed that they are highly susceptible to fracture.  Therefore, alternative approaches that allow the increase of root thickness and length should be pursued.
In recent times, a novel concept of revascularization of immature nonvital, infected teeth was introduced. The idea is to create and deliver new tissues to replace the necrotic pulp. 
| The concept|| |
Currently, there are two major concepts in the regenerative endodontics: Guided tissue regeneration and tissue engineering.
| Guided Tissue Regeneration (Revascularization)|| |
The guided tissue regeneration has now become widely known as the "revascularization" or "revitalization" approach. The concept of revascularization, per se was introduced by Ostby in 1960.  In 1971, Nygaard-Ostby and Hjortdal performed studies that can be considered the forerunner of pulpal regeneration. The studies were aimed at determining how periodontal tissue would react, if the entire pulp was removed from the main canal and the apical part subsequently allowed to be filled with blood. It was further demonstrated that in a traumatic avulsion, blood vessels slowly grow from the apex toward the pulp horn by replacing the necrosed pulp left behind after the avulsion injury. 
The development of normal, sterile granulation tissue within the root canal is thought to aid in revascularization and stimulation of cementoblasts or the undifferentiated mesenchymal cells at the periapex, leading to the deposition of a calcific material at the apex as well as on the lateral dentinal walls.
| Tissue engineering|| |
The second concept in the regenerative endodontics is tissue engineering where synthetic biodegradable materials were introduced as scaffolds for cell expansion. Currently, at least five different types of MSCs have been isolated from the dental tissues, including dental pulp stem cells (DPSC), stem cells of human exfoliated deciduous teeth (SHED), SCAP, dental follicle progenitor cells, and stem cells from periodontal ligament.  Among these, DPSC, SHED, and SCAP show stronger potential for pulp regeneration. However, it's further use in regenerative endodontic was halted due to the lack of isolation of specific dental stem cells.
| Case selection|| |
Case selection is important. It has been reported that pulp revascularization can occur most predictably in teeth with open apices.  An apical diameter of at least 1 mm (mesiodistally) radiographically is necessary to allow ingrowth of vital tissue. The presence of a periradicular radiolucency or a negative vitality test are not determining factors in case selection as vital pulp tissue or apical papilla may be present in the canal and at the apex. 
| Clinical procedures for revascularization through blood clotting|| |
It is important to understand the biological feature permitting revascularization in young avulsed tooth/necrotic tooth before it is clinically applied. These teeth have an open apex, short root and intact, but necrotic pulp tissue. Revascularization of the pulp space in infected immature teeth with apical periodontitis is impossible unless the canals are disinfected.
The blood clot revascularization method involves the following steps:
- During the first visit, minimal instrumentation and irrigation with 2.5% sodium hypochlorite for over 20 min after excavation of the coronal pulp.
- Disinfection with copious irrigation, and with the use of the "3 mix-MP" triple antibiotic paste, consisting of equal quantities of ciprofloxacin, metronidazole, and minocycline (concentration = 20 mg/ml) in propylene glycol or macrogol ointment (as a carrier), for a period of 3 weeks.
- In the second visit, mechanical irritation of the apex is performed with the use of a sterile K-file to initiate bleeding into the root canal to the level of cemento-enamel junction. A blood clot was produced to the level of the cemento-enamel junction to provide a scaffold for the in-growth of new tissue followed by a double seal of mineral trioxide aggregate in the cervical area and a bonded resin coronal restoration to prevent coronal bacterial ingress. 
Maintaining the viability of the remaining survived pulp tissue and the SCAP are considered critical for revascularization to succeed. Therefore, it is essential to follow a protocol of no canal instrumentation throughout the revascularization procedure in order preserve these essential enduring stem cells. ,, If this approach fails to regenerate new tissue, apexification is needed to achieve apex closure in order to perform conventional root canal therapy.
- Clinical and radiographic exam:
- No pain or soft tissue swelling (often observed between first and second appointments)
- Resolution of apical radiolucency (often observed 6-12 months after treatment)
- Increased width of root walls (this is generally observed before apparent increase in root length and often occurs 12-24 months after treatment)
- Increased root length
- Apical closure.
| Mechanism of revascularization|| |
- It is possible that a few vital pulp cells remain at the apical end of the root canal, which might proliferate into the newly formed matrix and differentiate into odontoblasts under the organizing influence of cells of Hertwig's epithelial root sheath, which are quite resistant to destruction, even in the presence of inflammation. 
- Another possible mechanism of continued root development could be due to multipotent DPSC,  which are present in permanent immature teeth in abundance. These cells from the apical end might be seeded onto the existing dentinal walls and might differentiate into odontoblasts and deposit tertiary or atubular dentin.
- The third possible mechanism could be attributed to the presence of stem cells in the periodontal ligament, , which can proliferate, grow into the apical end and within the root canal, and deposit hard tissue both at the apical end and on the lateral root walls.
- The fourth possible mechanism of root development could be attributed to SCAP or the bone marrow. Instrumentation beyond the confines of the root canal to induce bleeding can also transplant MSCs from the bone into the canal lumen. These cells have extensive proliferating capacity. ,
- Another possible mechanism could be that the blood clot itself, being a rich source of growth factors, could play an important role in regeneration, which include platelet-derived growth factor, vascular endothelial growth factor, platelet-derived epithelial growth factor, and tissue growth factor and could stimulate differentiation, growth, and maturation of fibroblasts, odontoblasts, cementoblasts, etc., from the immature, undifferentiated mesenchymal cells in the newly formed tissue matrix.
| Merits of revascularization|| |
Root canal revascularization through blood clotting is a relatively simple and practical approach, which can be accomplished with presently available instruments and materials. Moreover, the possibility of immune rejection and contamination can be averted since the root canal system is filled with patient's own blood cells.  Case reports have revealed progressive thickening of dentinal walls, continued root development, and positive response to thermal pulp testing. 
| Limitations|| |
- Difficult to achieve it in fully formed permanent teeth
- Potential clinical and biological complications such as crown discoloration, development of resistant bacterial strains (due to long-term use of antimicrobial agents), and allergic reaction to intracanal medicament.
- Potential risk of necrosis, if tissue is reinfected.
- The concentration and composition of the progenitor/stem cells entrapped in the fibrin clot is unpredictable, particularly in older patients and may lead to the disparity in the result.
- Lack of long-term follow-up studies makes revascularization procedure a supplement but not a substitute to the already existing treatment protocols such as apexogenesis, apexification, or partial pulpotomy. 
| Conclusion|| |
The success of revascularization points out the potential future fate of apexification procedures.
Such procedures may no longer be the preferred first option to treat immature permanent teeth with nonvital pulps. Based on the present studies, it is reasonable to conclude that revascularization is a reparative process rather than regenerative process. As the exact nature of the tissue formed inside the pulp canal in humans is not completely understood, it is better to consider revascularization therapy only when other conventional modalities of treatment like apexification, apexogenesis, and partial pulpotomy fail. The future research should focus on the issues that must be addressed to develop a safe, effective, and consistent method for regenerating a functional pulp-dentin complex.
| References|| |
|1.||Glossary of Endodontic Terms. 8 th ed. Chicago: American Association of Endodontists 2012. |
|2.||Hermann BW. On the reaction of the dental pulp to vital amputation and calxyl capping. Dtsch Zahnarztl Z 1952;7:1446-7. |
|3.||Garcia-Godoy F, Murray PE. Recommendations for using regenerative endodontic procedures in permanent immature traumatized teeth. Dent Traumatol 2012;28:33-41. |
|4.||Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: Biological basis of regenerative endodontic procedures. J Endod 2013;39:S30-43. |
|5.||Ding RY, Cheung GS, Chen J, Yin XZ, Wang QQ, Zhang CF. Pulp revascularization of immature teeth with apical periodontitis: A clinical study. J Endod 2009;35:745-9. |
|6.||Fuchs E, Segre JA. Stem cells: A new lease on life. Cell 2000;100:143-55. |
|7.||Mohammadi Z, Dummer PM. Properties and applications of calcium hydroxide in endodontics and dental traumatology. Int Endod J 2011;44:697-730. |
|8.||Torabinejad M, Chivian N. Clinical applications of mineral trioxide aggregate. J Endod 1999;25:197-205. |
|9.||Katebzadeh N, Dalton BC, Trope M. Strengthening immature teeth during and after apexification. J Endod 1998;24:256-9. |
|10.||Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: A review of current status and a call for action. J Endod 2007;33:377-90. |
|11.||Ostby BN. The role of the blood clot in endodontic therapy. An experimental histologic study. Acta Odontol Scand 1961;19:324-53. |
|12.||Kanaparthy A, Kanaparthy R, Muktishree M, Agarwal N. An old concept revisited- revascularization in endodontics- a case report. Int Oral Health 2011;3:50-4. |
|13.||Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: Their biology and role in regenerative medicine. J Dent Res 2009;88:792-806. |
|14.||Kling M, Cvek M, Mejare I. Rate and predictability of pulp revascularization in therapeutically reimplanted permanent incisors. Endod Dent Traumatol 1986;2:83-9. |
|15.||Huang GT. A paradigm shift in endodontic management of immature teeth: Conservation of stem cells for regeneration. J Dent 2008;36:379-86. |
|16.||Jung IY, Lee SJ, Hargreaves KM. Biologically based treatment of immature permanent teeth with pulpal necrosis: A case series. J Endod 2008;34:876-87. |
|17.||Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dent Traumatol 2001;17:185-7. |
|18.||Chueh LH, Huang GT. Immature teeth with periradicular periodontitis or abscess undergoing apexogenesis: A paradigm shift. J Endod 2006;32:1205-13. |
|19.||Saad AY. Calcium hydroxide and apexogenesis. Oral Surg Oral Med Oral Pathol 1988;66:499-501. |
|20.||Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, et al. Stem cell properties of human dental pulp stem cells. J Dent Res 2002;81:531-5. |
|21.||Lieberman J, Trowbridge H. Apical closure of nonvital permanent incisor teeth where no treatment was performed: Case report. J Endod 1983;9:257-60. |
|22.||Nevins A, Wrobel W, Valachovic R, Finkelstein F. Hard tissue induction into pulpless open-apex teeth using collagen-calcium phosphate gel. J Endod 1977;3:431-3. |
|23.||Krebsbach PH, Kuznetsov SA, Satomura K, Emmons RV, Rowe DW, Robey PG. Bone formation in vivo: Comparison of osteogenesis by transplanted mouse and human marrow stromal fibroblasts. Transplantation 1997;63:1059-69. |
|24.||Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 2000;97:13625-30. |
|25.||Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: New treatment protocol? J Endod 2004;30:196-200. |
|26.||Sakthi S, Bharadwaj SL. Pulp revascularisation in pediatric dentistry. J Int Dent 2012;1:34-6. |