Research Article
Volume 19 Issue 10 - 2020
Regenerative Endodontic Treatment in Clinical Practice: A Systematic Review
Hatem Faisal Bajnaid1*, Hussain Zaki Alabdulwahhab2, Abdulhadi Mohammed Albandar3, Khulud Nasser Alhmamey4, Rahaf Abdullah Manzalawi4, Nada Mohammed Fallatah5, Renad Khalid Alamoudi6, Reem Mohammed Alharbi6, Asuf Naif Alabdali7, Abdulmalik Ahmed Alburayk8 and Maryam Nabeel Nasser6
1Department of Endodontics, King Fahad Hospital, Jeddah, Saudi Arabia
2Primary Health Care, Ministry of Health, Ras Tanura, Saudi Arabia
3Primary Health Care, Ministry of Health, Hail, Saudi Arabia
4College of Dentistry, Batterjee Medical College, Jeddah, Saudi Arabia
5College of Dentistry, Alfarabi Colleges, Jeddah, Saudi Arabia
6College of Dentistry, Ibn Sina National College, Jeddah, Saudi Arabia
7General Dentist, FMC, Jeddah, Saudi Arabia
8College of Dentistry, Alfarabi Colleges, Riyadh, Saudi Arabia
*Corresponding Author: Hatem Faisal Bajnaid, Department of Endodontics, King Fahad Hospital, Jeddah, Saudi Arabia.
Received: August 12, 2020; Published: September 24, 2020


Recently, regenerative endodontic treatment (RET) has been recognized as a ‘paradigm shift’ regarding the management of immature teeth associated with pulp necrosis. Various reports have suggested the use of RET as a first-line therapeutic option when dealing with immature teeth, particularly when the roots are not yet fully developed. For that, a systematic electronic database search was conducted for relevant studies published from inception and till 24th June 2020 in seven databases. Several position statements and clinical recommendations regarding the use of RET in clinical practice have been released by the European Society of Endodontology (ESE) and the American Association of Endodontists (AAS). Such treatment modalities depend upon the tissue engineering concept components, including stem cells, scaffolds, and signaling molecules. In clinical practice, this treatment approach involves the process of disinfection and commonly the introduction of a blood clot into the root canal space. There are three main therapeutic goals of RET. The first goal is the resolution of associated clinical signs and symptoms. The second goal is to establish further root maturation. The final goal is the restoration of neurogenesis. Up till this point, RET has been unable to reach a proven result regarding the real regeneration of pulp tissue and dentine space. From a histological aspect, healing is achieved with repair from tissues that are originated mainly from the periodontal and osseous tissues, including bone-like tissues and cementum, rather than odontoblasts and pulp tissues. We have conducted the current literature review to provide an overview of the clinical and biological aspects of regenerative endodontic treatment.

Keywords: Regenerative; Endodontic; Treatment; Pulp: RET


  1. Rafter M. "Apexification: A Review”. Dental Traumatology 1 (2005): 1-8.
  2. Huang GT. "Apexification: The Beginning of Its End”. International Endodontic Journal 10 (2009): 855-866.
  3. Banchs F and M Trope. "Revascularization of Immature Permanent Teeth with Apical Periodontitis: New Treatment Protocol?" Journal of Endodontics 4 (2004): 196-200.
  4. Huang GT., et al. “The Hidden Treasure in Apical Papilla: The Potential Role in Pulp/Dentin Regeneration and Bioroot Engineering”. Journal of Endodontics 6 (2008): 645-651.
  5. Shah N., et al. “Efficacy of Revascularization to Induce Apexification/Apexogensis in Infected, Nonvital, Immature Teeth: A Pilot Clinical Study”. Journal of Endodontics 8 (2008): 919-925.
  6. Hoshino E., et al. “In-Vitro Antibacterial Susceptibility of Bacteria Taken from Infected Root Dentine to a Mixture of Ciprofloxacin, Metronidazole and Minocycline”. International Endodontic Journal 2 (1996): 125-130.
  7. Sato I., et al. “Sterilization of Infected Root-Canal Dentine by Topical Application of a Mixture of Ciprofloxacin, Metronidazole and Minocycline in Situ”. International Endodontic Journal 2 (1996): 118-124.
  8. Liberati Alessandro., et al. “The Prisma Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration”. PLoS Medicine7 (2009): e1000100.
  9. Vassar Matt., et al. “Manual Search Approaches Used by Systematic Reviewers in Dermatology”. Journal of the Medical Library Association: JMLA4 (2016): 302.
  10. Health, National Institutes of. "Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies”. National Heart, Lung, and Blood Institute (2014).
  11. Lin LM., et al. “Regeneration of the Dentine-Pulp Complex with Revitalization/Revascularization Therapy: Challenges and Hopes”. International Endodontic Journal 8 (2014): 713-724.
  12. Gronthos S., et al. “Stem Cell Properties of Human Dental Pulp Stem Cells”. Journal of Dental Research 8 (2002): 531-535.
  13. Chmilewsky F., et al. “Sources of Dentin-Pulp Regeneration Signals and Their Modulation by the Local Microenvironment”. Journal of Endodontics 4 (2014): S19-S25.
  14. Galler KM., et al. “Scaffolds for Dental Pulp Tissue Engineering”. Advances in Dental Research 3 (2011): 333-339.
  15. Ulusoy AT., et al. “Evaluation of Blood Clot, Platelet-Rich Plasma, Platelet-Rich Fibrin, and Platelet Pellet as Scaffolds in Regenerative Endodontic Treatment: A Prospective Randomized Trial”. Journal of Endodontics 5 (2019): 560-566.
  16. Jung C., et al. “Pulp-Dentin Regeneration: Current Approaches and Challenges”. Journal of Tissue Engineering 10 (2019): 2041731418819263.
  17. Hargreaves Kenneth M. “Pathways of the Pulp”. Mosby (2006).
  18. Bose R., et al. “A Retrospective Evaluation of Radiographic Outcomes in Immature Teeth with Necrotic Root Canal Systems Treated with Regenerative Endodontic Procedures”. Journal of Endodontics 10 (2009): 1343-1349.
  19. Lee BN., et al. “A Review of the Regenerative Endodontic Treatment Procedure”. Restorative Dentistry and Endodontics 3 (2015): 179-187.
  20. Cvek M. "Prognosis of Luxated Non-Vital Maxillary Incisors Treated with Calcium Hydroxide and Filled with Gutta-Percha. A Retrospective Clinical Study”. Endodontics and Dental Traumatology 2 (1992): 45-55.
  21. Kim SG., et al. “Regenerative Endodontics: A Comprehensive Review”. International Endodontic Journal 12 (2018): 1367-1388.
  22. Paryani K and SG Kim. "Regenerative Endodontic Treatment of Permanent Teeth after Completion of Root Development: A Report of 2 Cases”. Journal of Endodontics 7 (2013): 929-934.
  23. Endodontics, American Association of. "Aae Clinical Considerations for a Regenerative Procedure”. (2018).
  24. Myers WC and SB Fountain. "Dental Pulp Regeneration Aided by Blood and Blood Substitutes after Experimentally Induced Periapical Infection”. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 3 (1974): 441-450.
  25. Fouad AF. "Microbial Factors and Antimicrobial Strategies in Dental Pulp Regeneration”. Journal of Endodontics 9s (2017): S46-s50.
  26. Zehnder M. "Root Canal Irrigants”. Journal of Endodontics 5 (2006): 389-398.
  27. Kontakiotis EG., et al. “Regenerative Endodontic Therapy: A Data Analysis of Clinical Protocols”. Journal of Endodontics 2 (2015): 146-154.
  28. Galler KM., et al. “Influence of Root Canal Disinfectants on Growth Factor Release from Dentin”. Journal of Endodontics 3 (2015): 363-368.
  29. Martin DE., et al. “Concentration-Dependent Effect of Sodium Hypochlorite on Stem Cells of Apical Papilla Survival and Differentiation”. Journal of Endodontics 1 (2014): 51-55.
  30. Yamauchi N., et al. “Immunohistological Characterization of Newly Formed Tissues after Regenerative Procedure in Immature Dog Teeth”. Journal of Endodontics 12 (2011): 1636-1641.
  31. Galler KM., et al. “EDTA Conditioning of Dentine Promotes Adhesion, Migration and Differentiation of Dental Pulp Stem Cells”. International Endodontic Journal 6 (2016): 581-590.
  32. Trevino EG., et al. “Effect of Irrigants on the Survival of Human Stem Cells of the Apical Papilla in a Platelet-Rich Plasma Scaffold in Human Root Tips”. Journal of Endodontics 8 (2011): 1109-1115.
  33. Sjögren U., et al. “The Antimicrobial Effect of Calcium Hydroxide as a Short‐Term Intracanal Dressing”. International Endodontic Journal3 (1991): 119-125.
  34. Kitikuson P and T Srisuwan. "Attachment Ability of Human Apical Papilla Cells to Root Dentin Surfaces Treated with Either 3mix or Calcium Hydroxide”. Journal of Endodontics 1 (2016): 89-94.
  35. Andreasen JO., et al. “Long-Term Calcium Hydroxide as a Root Canal Dressing May Increase Risk of Root Fracture”. Dental Traumatology 3 (2002): 134-137.
  36. Kahler SL., et al. “The Effect of Long-Term Dressing with Calcium Hydroxide on the Fracture Susceptibility of Teeth”. Journal of Endodontics 3 (2018): 464-469.
  37. Althumairy RI., et al. “Effect of Dentin Conditioning with Intracanal Medicaments on Survival of Stem Cells of Apical Papilla”. Journal of Endodontics 4 (2014): 521-525.
  38. Cehreli ZC., et al. “Regenerative Endodontic Treatment (Revascularization) of Immature Necrotic Molars Medicated with Calcium Hydroxide: A Case Series”. Journal of Endodontics 9 (2011): 1327-1330.
  39. Lovelace TW., et al. “Evaluation of the Delivery of Mesenchymal Stem Cells into the Root Canal Space of Necrotic Immature Teeth after Clinical Regenerative Endodontic Procedure”. Journal of Endodontics 2 (2011): 133-138.
  40. Kahler B., et al. “Revascularization Outcomes: A Prospective Analysis of 16 Consecutive Cases”. Journal of Endodontics 3 (2014): 333-338.
  41. Chen MY., et al. “Responses of Immature Permanent Teeth with Infected Necrotic Pulp Tissue and Apical Periodontitis/Abscess to Revascularization Procedures”. International Endodontic Journal 3 (2012): 294-305.
  42. Song M., et al. “Revascularization-Associated Intracanal Calcification: Assessment of Prevalence and Contributing Factors”. Journal of Endodontics 12 (2017): 2025-2033.
  43. Majno Guido and Isabelle Joris. “Cells, Tissues, and Disease: Principles of General Pathology. Oxford University Press (2004).
  44. Lin LM and PA Rosenberg. "Repair and Regeneration in Endodontics”. International Endodontic Journal10 (2011): 889-906.
  45. Da Silva LA., et al. “Revascularization and Periapical Repair after Endodontic Treatment Using Apical Negative Pressure Irrigation Versus Conventional Irrigation Plus Triantibiotic Intracanal Dressing in Dogs' Teeth with Apical Periodontitis”. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 5 (2010): 779-787.
  46. Wang X., et al. “Histologic Characterization of Regenerated Tissues in Canal Space after the Revitalization/Revascularization Procedure of Immature Dog Teeth with Apical Periodontitis”. Journal of Endodontics 1 (2010): 56-63.
  47. Yamauchi N., et al. “Tissue Engineering Strategies for Immature Teeth with Apical Periodontitis”. Journal of Endodontics 3 (2011): 390-397.
  48. Becerra P., et al. “Histologic Study of a Human Immature Permanent Premolar with Chronic Apical Abscess after Revascularization/Revitalization”. Journal of Endodontics 1 (2014): 133-139.
  49. Lin LM., et al. “Histologic and Histobacteriologic Observations of Failed Revascularization/Revitalization Therapy: A Case Report”. Journal of Endodontics 2 (2014): 291-295.
  50. Lin LM., et al. “Continued Root Maturation Despite Persistent Apical Periodontitis of Immature Permanent Teeth after Failed Regenerative Endodontic Therapy”. Australian Endodontic Journal 3 (2018): 292-299.
  51. Linsuwanont P., et al. “Evaluation of Root Maturation after Revitalization in Immature Permanent Teeth with Nonvital Pulps by Cone Beam Computed Tomography and Conventional Radiographs”. International Endodontic Journal 9 (2017): 836-846.
  52. Žižka R., et al. “Root Maturation in Teeth Treated by Unsuccessful Revitalization: 2 Case Reports”. Journal of Endodontics 5 (2016): 724-729.
  53. Shimizu Emi., et al. “Clinical, Radiographic, and Histological Observation of a Human Immature Permanent Tooth with Chronic Apical Abscess after Revitalization Treatment”. Journal of endodontics8 (2013): 1078-1083.
  54. Kahler B., et al. “An Evidence-Based Review of the Efficacy of Treatment Approaches for Immature Permanent Teeth with Pulp Necrosis”. Journal of Endodontics 7 (2017): 1052-1057.
  55. Lin J., et al. “Regenerative Endodontics Versus Apexification in Immature Permanent Teeth with Apical Periodontitis: A Prospective Randomized Controlled Study”. Journal of Endodontics 11 (2017): 1821-1827.
  56. Silujjai J and P Linsuwanont. "Treatment Outcomes of Apexification or Revascularization in Nonvital Immature Permanent Teeth: A Retrospective Study”. Journal of Endodontics 2 (2017): 238-245.
Citation: Hatem Faisal Bajnaid., et al. “Regenerative Endodontic Treatment in Clinical Practice: A Systematic Review”. EC Dental Science 19.10 (2020): 95-106.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

April Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the April issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for upcoming Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before May 04, 2021.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to