Rooted in Regeneration: An Overview on Regenerative Endodontics
Main Article Content
Abstract
Regenerative endodontic procedures (REPs) are a relatively recent treatment option in dentistry. Although, the roots of its underlying principles can be traced to the early 1970s, the first clinical application did not take place until 2001. These procedures can help revolutionize the treatment of immature permanent teeth, where the development of the root has ceased due to the infection destroying the capabilities of the tooth to do so.
The conventional treatment modality of apexification, simply involved the formation of a hard tissue barrier, upon which conventional obturation of the root canal system was performed. However, this method does not reinforce the structurally compromised root. In contrast, REPs not only eradicate infection but also promote continued root development, increasing both root length and dentinal wall thickness.
Current clinical evidence supports a favourable prognosis for REPs, particularly in achieving disinfection. In cases of failure, the procedure can be repeated or alternative treatments such as apexification or conventional non-surgical root canal therapy may be employed, offering clinicians multiple management pathways, which can be presented to patients. This article reviews clinical considerations and recommended protocols, providing clinicians with comprehensive data to support implementation in practice.
Article Details
How to Cite
ARIWALA, Dr. Farhan Iqbal; CALCUTTAWALA, Dr. Maria Shabbir.
Rooted in Regeneration: An Overview on Regenerative Endodontics.
Medical Research Archives, [S.l.], v. 13, n. 10, oct. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6981>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i10.6981.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1) Nygaard‐östby B, Hjortdal O. Tissue formation in the root canal following pulp removal. European Journal of Oral Sciences. 1971;79(3):333-349. doi:10.1111/j.1600-0722.1971.tb02019.x
2) Iwaya S, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dental Traumatology. 2001;17(4):185-187. doi:10.1034/j.1600-9657.2001.017004185.x
3) Trope M. Reply. Journal of Endodontics. 2008;34(5):511-512. doi:10.1016/j.joen.2008.02.010
4) Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative Endodontics: a review of current status and a call for action. Journal of Endodontics. 2007;33(4):377-390. doi:10.1016/j.joen.2006.09.013
5) Rafter M. Apexification: a review. Dental Traumatology. 2005;21(1):1-8. doi:10.1111/j.1600-9657.2004.00284.x
6) Kim SG, Malek M, Sigurdsson A, Lin LM, Kahler B. Regenerative endodontics: a comprehensive review. International Endodontic Journal. 2018;51(12):1367-1388. doi:10.1111/iej.12954
7) Almutairi W, Yassen GH, Aminoshariae A, Williams KA, Mickel A. Regenerative Endodontics: A systematic analysis of the failed cases. Journal of Endodontics. 2019;45(5):567-577. doi:10.1016/j.joen.2019.02.004
8) Valsan D, Pulyodan M, Mohan S, Divakar N, Moyin S, Thayyil S. Regenerative endodontics: A paradigm shift in clinical endodontics. Journal of Pharmacy and Bioallied Sciences. 2020;12(5):20. doi:10.4103/jpbs.jpbs_112_20
9) Galler KM, Krastl G, Simon S, et al. European Society of Endodontology position statement: Revitalization procedures. International Endodontic Journal. 2016;49(8):717-723. doi:10.1111/iej.12629
10) Ricucci D, Siqueira JF, Loghin S, Lin LM. Pulp and apical tissue response to deep caries in immature teeth: A histologic and histobacteriologic study. Journal of Dentistry. 2016;56:19-32. doi:10.1016/j.jdent.2016.10.005
11) Horan MA, Ashcroft GS. Ageing, defence mechanisms and the immune system. Age And Ageing. 1997;26(suppl 4):15-19. doi:10.1093/ageing/26.suppl_4.15
12) Chen MY ‐h., Chen K ‐l., Chen C ‐a., Tayebaty F, Rosenberg PA, Lin LM. Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures. International Endodontic Journal. 2011;45 (3):294-305. doi:10.1111/j.1365-2591.2011.0197 8.x
13) Kontakiotis EG, Filippatos CG, Tzanetakis GN, Agrafioti A. Regenerative Endodontic therapy: A data analysis of clinical protocols. Journal of Endodontics. 2014;41(2):146-154. doi:10.1016/j.joen.2014.08.003
14) Diogenes A, Henry MA, Teixeira FB, Hargreaves KM. An update on clinical regenerative endodontics. Endodontic Topics. 2013;28(1):2-23. doi:10.1111/ etp.12040
15) AAE Clinical Considerations for a Regenerative Procedure Revised 2021. aae.org. https://www.aae.org/specialty/wp-content/uploads/sites/2/2021/08/ClinicalConsiderationsApprovedByREC062921.pdf. Published 2021. Accessed August 10, 2025.
16) Siqueira JF. Reaction of periradicular tissues to root canal treatment: benefits and drawbacks. Endodontic Topics. 2005;10(1):123-147. doi:10.1111/j.1601-1546.2005.00134.x
17) Fang Y, Wang X, Zhu J, Su C, Yang Y, Meng L. Influence of Apical Diameter on the Outcome of Regenerative Endodontic Treatment in Teeth with Pulp Necrosis: A Review. Journal of Endodontics. 2017;44(3):414-431. doi:10.1016/j.joen.2017.10.007
18) Estefan BS, Batouty KME, Nagy MM, Diogenes A. Influence of age and apical diameter on the success of endodontic regeneration procedures. Journal of Endodontics. 2016;42(11):1620-1625. doi:10.1016/j.joen.2016.06.020
19) Alothman FA, Hakami LS, Alnasser A, AlGhamdi FM, Alamri AA, Almutairii BM. Recent Advances in Regenerative Endodontics: A review of current techniques and future directions. Cureus. November 2024. doi:10.7759/cureus.74121
20) Kim S. Infection and pulp regeneration. Dentistry Journal. 2016;4(1):4. doi:10.3390/dj4010004
21) Wang X, Thibodeau B, Trope M, Lin LM, Huang GT j. Histologic Characterization of Regenerated Tissues in Canal Space after the Revitalization/ Revascularization Procedure of Immature Dog Teeth with Apical Periodontitis. Journal of Endodontics. 2009;36(1):56-63. doi:10.1016/j.joen.2009.09.039
22) Becerra P, Ricucci D, Loghin S, Gibbs JL, Lin LM. Histologic Study of a Human Immature Permanent Premolar with Chronic Apical Abscess after Revascularization/Revitalization. Journal of Endodontics. 2013;40(1):133-139. doi:10.1016/j.joen.2013.07.017
23) Lei L, Chen Y, Zhou R, Huang X, Cai Z. Histologic and Immunohistochemical Findings of a Human Immature Permanent Tooth with Apical Periodontitis after Regenerative Endodontic Treatment. Journal of Endodontics. 2015;41(7):1172-1179. doi:10.1016/j.joen.2015.03.012
24) Fouad AF. Microbial factors and antimicrobial strategies in dental pulp regeneration. Journal of Endodontics. 2017;43(9):S46-S50. doi:10.1016/j.joen.2017.06.010
25) 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, 88:792-806.10.1177/ 0022034509340867
26) Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic‐Canic M. PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing. Wound Repair and Regeneration. 2008;16(5):585-601. doi:10.1111/j.1524-475x.2008.00410.x
27) Galler KM, Buchalla W, Hiller KA, et al. Influence of Root Canal Disinfectants on Growth Factor Release from Dentin. Journal of Endodontics. 2015;41(3):363-368. doi:10.1016/j.joen.2014.11.021
28) Sadaghiani L, Alshumrani AM, Gleeson HB, Ayre WN, Sloan AJ. Growth factor release and dental pulp stem cell attachment following dentine conditioning: An in vitro study. International Endodontic Journal. 2022; 55(8):858-869. doi:10.1111/iej.13781
29) Vo TN, Kasper FK, Mikos AG. Strategies for controlled delivery of growth factors and cells for bone regeneration. Advanced Drug Delivery Reviews. 2012;64(12):1292-1309. doi:10.1016/j.addr.2012.01.016
30) Kim SG. Biological molecules for the regeneration of the Pulp-Dentin complex. Dental Clinics of North America. 2016;61(1):127-141. doi:10.1016/j.cden.2016.08.005
31) Alamoudi R. The smear layer in endodontic: To keep or remove – an updated overview. Deleted Journal. 2019;9(2):71. doi:10.4103/sej.sej_95_18
32) Sena NT, Gomes BPFA, Vianna ME, et al. In vitro antimicrobial activity of sodium hypochlorite and chlorhexidine against selected single‐species biofilms. International Endodontic Journal. 2006;39(11):878-885. doi:10.1111/j.1365-2591.2006.01161.x
33) Sena NT, Gomes BPFA, Vianna ME, et al. In vitro antimicrobial activity of sodium hypochlorite and chlorhexidine against selected single‐species biofilms. International Endodontic Journal. 2006;39(11):878-885. doi:10.1111/j.1365-2591.2006.01161.x
34) Martin DE, De Almeida JFA, Henry MA, et al. Concentration-dependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation. Journal of Endodontics. 2013;40(1):51-55. doi:10.1016/j.joen.2013.07.026
35) Trevino EG, Patwardhan AN, Henry MA, 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. 2011;37(8): 1109-1115. doi:10.1016/j.joen.2011.05.013
36) C E, Gb S, Ll B, O FJ. Mechanism of action of calcium and hydroxyl ions of calcium hydroxide on tissue and bacteria. PubMed. 1995;6(2):85-90. https://pubmed.ncbi.nlm.nih.gov/8688662.
37) Kitikuson P, Srisuwan T. Attachment Ability of Human Apical Papilla Cells to Root Dentin Surfaces Treated with Either 3Mix or Calcium Hydroxide. Journal of Endodontics. 2015;42(1):89-94. doi:10.1016/j.joen.2015.08.021
38) Nagata JY, Soares AJ, Souza-Filho FJ, et al. Microbial Evaluation of Traumatized Teeth Treated with Triple Antibiotic Paste or Calcium Hydroxide with 2% Chlorhexidine Gel in Pulp Revascularization. Journal of Endodontics. 2014;40(6):778-783. doi:10.1016/j.joen.2014.01.038
39) Grossman L. Antimicrobial effect of root canal cements. Journal of Endodontics. 1980;6(6):594-597. doi:10.1016/s0099-2399(80)80019-7
40) 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. International Endodontic Journal. 1996;29(2):125-130. doi:10.1111/j.1365-2591.1996.tb01173.x
41) 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. International Endodontic Journal. 1996;29(2):118-124. doi:10.1111/j.1365-2591.1996.tb01172.x
42) Nosrat A, Li KL, Vir K, Hicks ML, Fouad AF. Is pulp regeneration necessary for root maturation? Journal of Endodontics. 2013;39(10):1291-1295. doi:10.1016/j.joen.2013.06.019
43) Baumgartner J, Xia T. Antibiotic Susceptibility of Bacteria Associated with Endodontic Abscesses. Journal of Endodontics. 2003;29(1):44-47. doi:10.1097/00004770-200301000-00012
44) Sharma S, Bhushan U, Goswami M, Baveja C. Comparative evaluation of two antibiotic pastes for root canal disinfection. International Journal of Clinical Pediatric Dentistry. 2022;15(S1):S12-S17. doi:10.5005/jp-journals-10005-1898
45) Baziar M, Mehrasebi MR, Assadi A, Fazli MM, Maroosi M, Rahimi F. Erratum to: Efficiency of non-ionic surfactants - EDTA for treating TPH and heavy metals from contaminated soil. Journal of Environmental Health Science and Engineering. 2014;12(1). doi:10.1186/2052-336x-12-47
46) Galler KM, D’Souza RN, Federlin M, et al. Dentin Conditioning codetermines cell fate in regenerative endodontics. Journal of Endodontics. 2011;37(11): 1536-1541. doi:10.1016/j.joen.2011.08.027
47) Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB. Challenges in Regenerative Endodontics: a case series. Journal of Endodontics. 2009;36(3):536-541. doi:10.1016/j.joen.2009.10.006
48) Nosrat A, Homayounfar N, Oloomi K. Drawbacks and unfavorable outcomes of regenerative endodontic treatments of necrotic immature teeth: a literature review and report of a case. Journal of Endodontics. 2012;38(10):1428-1434. doi:10.1016/j.joen.2012.06.025
49) Caviedes‐Bucheli J, Muñoz‐Alvear HD, Lopez‐Moncayo LF, et al. Use of scaffolds and regenerative materials for the treatment of immature necrotic permanent teeth with periapical lesion: Umbrella review. International Endodontic Journal. 2022;55 (10):967-988. doi:10.1111/iej.13799
50) Torabinejad M, Turman M. Revitalization of Tooth with Necrotic Pulp and Open Apex by Using Platelet-rich Plasma: A Case Report. Journal of Endodontics. 2011;37(2):265-268. doi:10.1016/j.joen.2010.11.004
51) Jadhav G, Shah N, Logani A. Revascularization with and without Platelet-rich Plasma in Nonvital, Immature, Anterior Teeth: A Pilot Clinical Study. Journal of Endodontics. 2012;38(12):1581-1587. doi:10.1016/j.joen.2012.09.010
52) Bezgin T, Yilmaz AD, Celik BN, Kolsuz ME, Sonmez H. Efficacy of platelet-rich plasma as a scaffold in regenerative endodontic treatment. Journal of Endodontics. 2014;41(1):36-44. doi:10.1016/j.joen.2014.10.004
53) Bakhtiar H, Esmaeili S, Tabatabayi SF, Ellini MR, Nekoofar MH, Dummer PMH. Second-generation platelet concentrate (Platelet-rich fibrin) as a scaffold in regenerative endodontics: a case series. Journal of Endodontics. 2017;43(3):401-408. doi:10.1016/j.joen.2016.10.016
54) Narang I, Mittal N, Mishra N. A comparative evaluation of the blood clot, platelet-rich plasma, and platelet-rich fibrin in regeneration of necrotic immature permanent teeth: A clinical study. Contemporary Clinical Dentistry. 2015;6(1):63. doi:10.4103/0976-237x.149294
55) Lolato A, Bucchi C, Taschieri S, Kabbaney AE, Del Fabbro M. Platelet concentrates for revitalization of immature necrotic teeth: a systematic review of the clinical studies. Platelets. 2016;27(5):383-392. doi:10.3109/09537104.2015.1131255
56) Zhou R, Wang Y, Chen Y, et al. Radiographic, Histologic, and Biomechanical Evaluation of Combined Application of Platelet-rich Fibrin with Blood Clot in Regenerative Endodontics. Journal of Endodontics. 2017;43(12):2034-2040. doi:10.1016/j.joen.2017.07.021
57) Aksel H, Serper A: Recent considerations in regenerative endodontic treatment approaches . J Dent. 2014, 9:1-7. 10.1016/j.jds.2013.12.007
58) Antunes LS, Salles AG, Gomes CC, Andrade TB, Delmindo MP, Antunes L a. A. The effectiveness of pulp revascularization in root formation of necrotic immature permanent teeth: A systematic review. Acta Odontologica Scandinavica. 2015;74(3):161-169. doi:10.3109/00016357.2015.1069394
59) Tong HJ, Rajan S, Bhujel N, Kang J, Duggal M, Nazzal H. Regenerative Endodontic Therapy in the Management of Nonvital Immature Permanent Teeth: A Systematic Review—Outcome Evaluation and Meta-analysis. Journal of Endodontics. 2017;43(9):14 53-1464. doi:10.1016/j.joen.2017.04.018
60) Torabinejad M, Nosrat A, Verma P, Udochukwu O. Regenerative Endodontic Treatment or Mineral Trioxide Aggregate Apical Plug in Teeth with Necrotic Pulps and Open Apices: A Systematic Review and Meta-analysis. Journal of Endodontics. 2017;43(11):1806-1820. doi:10.1016/j.joen.2017.06.029
61) Alghamdi F, Alsulaimani M. Regenerative endodontic treatment: A systematic review of successful clinical cases. Dental and Medical Problems. 2021;58(4):555-567. doi:10.17219/dmp/132181
62) Kahler B, Mistry S, Moule A, et al. Revascularization outcomes: A prospective analysis of 16 consecutive cases. Journal of Endodontics. 2013;40(3):333-338. doi:10.1016/j.joen.2013.10.032
63) Alobaid AS, Cortes LM, Lo J, et al. Radiographic and clinical outcomes of the treatment of immature permanent teeth by revascularization or apexification: a pilot retrospective cohort study. Journal of Endodontics. 2014;40(8):1063-1070. doi:10.1016/j.joen.2014.02.016
64) Saoud TMA, Zaazou A, Nabil A, Moussa S, Lin LM, Gibbs JL. Clinical and Radiographic Outcomes of Traumatized Immature Permanent Necrotic Teeth after Revascularization/Revitalization Therapy. Journal of Endodontics. 2014;40(12):1946-1952. doi:10.1016/j.joen.2014.08.023
65) Li L, Pan Y, Mei L, Li J. Clinical and Radiographic Outcomes in Immature Permanent Necrotic Evaginated Teeth Treated with Regenerative Endodontic Procedures. Journal of Endodontics. 2016; 43(2):246-251. doi:10.1016/j.joen.2016.10.015
66) Nageh M, Ahmed GM, El-Baz AA. Assessment of Regaining Pulp Sensibility in Mature Necrotic Teeth Using a Modified Revascularization Technique with Platelet-rich Fibrin: A Clinical Study. Journal of Endodontics. 2018;44(10):1526-1533. doi:10.1016/j.joen.2018.06.014
67) Parirokh M, Torabinejad M. Mineral Trioxide Aggregate: A Comprehensive Literature Review—Part III: Clinical Applications, Drawbacks, and Mechanism of Action. Journal of Endodontics. 2010;36(3):400-413. doi:10.1016/j.joen.2009.09.009
68) Marconyak LJ, Kirkpatrick TC, Roberts HW, et al. A comparison of coronal tooth discoloration elicited by various endodontic reparative materials. Journal of Endodontics. 2015;42(3):470-473. doi:10.1016/j.joen.2015.10.013
69) Shokouhinejad N, Nekoofar MH, Pirmoazen S, Shamshiri AR, Dummer PMH. Evaluation and Comparison of Occurrence of Tooth Discoloration after the Application of Various Calcium Silicate–based Cements: An Ex Vivo Study. Journal of Endodontics. 2015;42(1):140-144. doi:10.1016/j.joen.2015.08.034
70) Kirchhoff AL, Raldi DP, Salles AC, Cunha RS, Mello I. Tooth discolouration and internal bleaching after the use of triple antibiotic paste. International Endodontic Journal. 2014;48(12):1181-1187. doi:10.1111/iej.12423
71) Thibodeau B, Teixeira F, Yamauchi M, Caplan DJ, Trope M. Pulp revascularization of immature dog teeth with apical periodontitis. Journal of Endodontics. 2007;33(6):680-689. doi:10.1016/j.joen.2007.03.001
72) Yamauchi N, Yamauchi S, Nagaoka H, et al. Tissue Engineering Strategies for Immature Teeth with Apical Periodontitis. Journal of Endodontics. 2011;37(3):390-397. doi:10.1016/j.joen.2010.11.010
73) Arslan H, Şahin Y, Topçuoğlu HS, Gündoğdu B. Histologic Evaluation of Regenerated Tissues in the Pulp Spaces of Teeth with Mature Roots at the Time of the Regenerative Endodontic Procedures. Journal of Endodontics. 2019;45(11):1384-1389. doi:10.1016/j.joen.2019.07.016
74) Topçuoğlu G, Topçuoğlu HS. Regenerative endodontic therapy in a single visit using platelet-rich plasma and biodentine in necrotic and asymptomatic immature molar teeth: a report of 3 cases. Journal of Endodontics. 2016;42(9):1344-1346. doi:10.1016/j.joen.2016.06.005
75) Chaniotis A. The use of a single‐step regenerative approach for the treatment of a replanted mandibular central incisor with severe resorption. International Endodontic Journal. 2015;49(8):802-812. doi:10.1111/iej.12515
76) Nassar MA, Roshdy NN, Kataia M, Mousa H, Sabet N. Assessment of the Clinical Outcomes of Single Visit Regenerative Endodontic Procedure In Treating Necrotic Mature Teeth with Apical Periodontitis Using Biological Irrigating Solution. Open Access Macedonian Journal of Medical Sciences. 2023;11(D): 61-64. doi:10.3889/oamjms.2023.11314
77) McCabe P. Revascularization of an immature tooth with apical periodontitis using a single visit protocol: a case report. International Endodontic Journal. 2014;48(5):484-497. doi:10.1111/iej.12344
78) Conde MCM, 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. International Endodontic Journal. 2016;50(9):860-874. doi:10.1111/iej.12711
79) Song M, Cao Y, Shin SJ, et al. Revascularization-associated intracanal calcification: Assessment of prevalence and contributing factors. Journal of Endodontics. 2017;43(12):2025-2033. doi:10.1016/j.joen.2017.06.018
80) Silujjai J, Linsuwanont P. Treatment Outcomes of apexification or revascularization in nonvital immature permanent teeth: a retrospective study. Journal of Endodontics. 2017;43(2):238-245. doi:10.1016/j.joen.2016.10.030
81) Lin J, Zeng Q, Wei X, et al. Regenerative Endodontics Versus Apexification in Immature Permanent Teeth with Apical Periodontitis: A Prospective Randomized Controlled Study. Journal of Endodontics. 2017;43(11):1821-1827. doi:10.1016/j.joen.2017.06.023
82) 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. Journal of Endodontics. 2009;35(10):1343-1349. doi:10.1016/j.joen.2009.06.021
83) De Toubes KMS, De Oliveira PAD, Machado SN, Pelosi V, Nunes E, Silveira FF. Clinical Approach to Pulp Canal Obliteration: A case series. PubMed. 2017;12(4):527-533. doi:10.22037/iej.v12i4.18006
84) Žižka R, Buchta T, Voborná I, Harvan L, Šedý J. Root maturation in teeth treated by unsuccessful revitalization: 2 case reports. Journal of Endodontics. 2016;42(5):724-729. doi:10.1016/j.joen.2016.02.004
85) Chaniotis A. Treatment options for failing regenerative endodontic procedures: Report of 3 cases. Journal of Endodontics. 2017;43(9):1472-1478. doi:10.1016/j.joen.2017.04.015
86) Keinan D, Nuni E, Rainus MB, Simhon TB, Dakar A, Slutzky-Goldberg I. Retreatment of failed regenerative Endodontic therapy: outcome and treatment considerations. Cureus. December 2024. doi:10.7759/cureus.75147
2) Iwaya S, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dental Traumatology. 2001;17(4):185-187. doi:10.1034/j.1600-9657.2001.017004185.x
3) Trope M. Reply. Journal of Endodontics. 2008;34(5):511-512. doi:10.1016/j.joen.2008.02.010
4) Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative Endodontics: a review of current status and a call for action. Journal of Endodontics. 2007;33(4):377-390. doi:10.1016/j.joen.2006.09.013
5) Rafter M. Apexification: a review. Dental Traumatology. 2005;21(1):1-8. doi:10.1111/j.1600-9657.2004.00284.x
6) Kim SG, Malek M, Sigurdsson A, Lin LM, Kahler B. Regenerative endodontics: a comprehensive review. International Endodontic Journal. 2018;51(12):1367-1388. doi:10.1111/iej.12954
7) Almutairi W, Yassen GH, Aminoshariae A, Williams KA, Mickel A. Regenerative Endodontics: A systematic analysis of the failed cases. Journal of Endodontics. 2019;45(5):567-577. doi:10.1016/j.joen.2019.02.004
8) Valsan D, Pulyodan M, Mohan S, Divakar N, Moyin S, Thayyil S. Regenerative endodontics: A paradigm shift in clinical endodontics. Journal of Pharmacy and Bioallied Sciences. 2020;12(5):20. doi:10.4103/jpbs.jpbs_112_20
9) Galler KM, Krastl G, Simon S, et al. European Society of Endodontology position statement: Revitalization procedures. International Endodontic Journal. 2016;49(8):717-723. doi:10.1111/iej.12629
10) Ricucci D, Siqueira JF, Loghin S, Lin LM. Pulp and apical tissue response to deep caries in immature teeth: A histologic and histobacteriologic study. Journal of Dentistry. 2016;56:19-32. doi:10.1016/j.jdent.2016.10.005
11) Horan MA, Ashcroft GS. Ageing, defence mechanisms and the immune system. Age And Ageing. 1997;26(suppl 4):15-19. doi:10.1093/ageing/26.suppl_4.15
12) Chen MY ‐h., Chen K ‐l., Chen C ‐a., Tayebaty F, Rosenberg PA, Lin LM. Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures. International Endodontic Journal. 2011;45 (3):294-305. doi:10.1111/j.1365-2591.2011.0197 8.x
13) Kontakiotis EG, Filippatos CG, Tzanetakis GN, Agrafioti A. Regenerative Endodontic therapy: A data analysis of clinical protocols. Journal of Endodontics. 2014;41(2):146-154. doi:10.1016/j.joen.2014.08.003
14) Diogenes A, Henry MA, Teixeira FB, Hargreaves KM. An update on clinical regenerative endodontics. Endodontic Topics. 2013;28(1):2-23. doi:10.1111/ etp.12040
15) AAE Clinical Considerations for a Regenerative Procedure Revised 2021. aae.org. https://www.aae.org/specialty/wp-content/uploads/sites/2/2021/08/ClinicalConsiderationsApprovedByREC062921.pdf. Published 2021. Accessed August 10, 2025.
16) Siqueira JF. Reaction of periradicular tissues to root canal treatment: benefits and drawbacks. Endodontic Topics. 2005;10(1):123-147. doi:10.1111/j.1601-1546.2005.00134.x
17) Fang Y, Wang X, Zhu J, Su C, Yang Y, Meng L. Influence of Apical Diameter on the Outcome of Regenerative Endodontic Treatment in Teeth with Pulp Necrosis: A Review. Journal of Endodontics. 2017;44(3):414-431. doi:10.1016/j.joen.2017.10.007
18) Estefan BS, Batouty KME, Nagy MM, Diogenes A. Influence of age and apical diameter on the success of endodontic regeneration procedures. Journal of Endodontics. 2016;42(11):1620-1625. doi:10.1016/j.joen.2016.06.020
19) Alothman FA, Hakami LS, Alnasser A, AlGhamdi FM, Alamri AA, Almutairii BM. Recent Advances in Regenerative Endodontics: A review of current techniques and future directions. Cureus. November 2024. doi:10.7759/cureus.74121
20) Kim S. Infection and pulp regeneration. Dentistry Journal. 2016;4(1):4. doi:10.3390/dj4010004
21) Wang X, Thibodeau B, Trope M, Lin LM, Huang GT j. Histologic Characterization of Regenerated Tissues in Canal Space after the Revitalization/ Revascularization Procedure of Immature Dog Teeth with Apical Periodontitis. Journal of Endodontics. 2009;36(1):56-63. doi:10.1016/j.joen.2009.09.039
22) Becerra P, Ricucci D, Loghin S, Gibbs JL, Lin LM. Histologic Study of a Human Immature Permanent Premolar with Chronic Apical Abscess after Revascularization/Revitalization. Journal of Endodontics. 2013;40(1):133-139. doi:10.1016/j.joen.2013.07.017
23) Lei L, Chen Y, Zhou R, Huang X, Cai Z. Histologic and Immunohistochemical Findings of a Human Immature Permanent Tooth with Apical Periodontitis after Regenerative Endodontic Treatment. Journal of Endodontics. 2015;41(7):1172-1179. doi:10.1016/j.joen.2015.03.012
24) Fouad AF. Microbial factors and antimicrobial strategies in dental pulp regeneration. Journal of Endodontics. 2017;43(9):S46-S50. doi:10.1016/j.joen.2017.06.010
25) 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, 88:792-806.10.1177/ 0022034509340867
26) Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic‐Canic M. PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing. Wound Repair and Regeneration. 2008;16(5):585-601. doi:10.1111/j.1524-475x.2008.00410.x
27) Galler KM, Buchalla W, Hiller KA, et al. Influence of Root Canal Disinfectants on Growth Factor Release from Dentin. Journal of Endodontics. 2015;41(3):363-368. doi:10.1016/j.joen.2014.11.021
28) Sadaghiani L, Alshumrani AM, Gleeson HB, Ayre WN, Sloan AJ. Growth factor release and dental pulp stem cell attachment following dentine conditioning: An in vitro study. International Endodontic Journal. 2022; 55(8):858-869. doi:10.1111/iej.13781
29) Vo TN, Kasper FK, Mikos AG. Strategies for controlled delivery of growth factors and cells for bone regeneration. Advanced Drug Delivery Reviews. 2012;64(12):1292-1309. doi:10.1016/j.addr.2012.01.016
30) Kim SG. Biological molecules for the regeneration of the Pulp-Dentin complex. Dental Clinics of North America. 2016;61(1):127-141. doi:10.1016/j.cden.2016.08.005
31) Alamoudi R. The smear layer in endodontic: To keep or remove – an updated overview. Deleted Journal. 2019;9(2):71. doi:10.4103/sej.sej_95_18
32) Sena NT, Gomes BPFA, Vianna ME, et al. In vitro antimicrobial activity of sodium hypochlorite and chlorhexidine against selected single‐species biofilms. International Endodontic Journal. 2006;39(11):878-885. doi:10.1111/j.1365-2591.2006.01161.x
33) Sena NT, Gomes BPFA, Vianna ME, et al. In vitro antimicrobial activity of sodium hypochlorite and chlorhexidine against selected single‐species biofilms. International Endodontic Journal. 2006;39(11):878-885. doi:10.1111/j.1365-2591.2006.01161.x
34) Martin DE, De Almeida JFA, Henry MA, et al. Concentration-dependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation. Journal of Endodontics. 2013;40(1):51-55. doi:10.1016/j.joen.2013.07.026
35) Trevino EG, Patwardhan AN, Henry MA, 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. 2011;37(8): 1109-1115. doi:10.1016/j.joen.2011.05.013
36) C E, Gb S, Ll B, O FJ. Mechanism of action of calcium and hydroxyl ions of calcium hydroxide on tissue and bacteria. PubMed. 1995;6(2):85-90. https://pubmed.ncbi.nlm.nih.gov/8688662.
37) Kitikuson P, Srisuwan T. Attachment Ability of Human Apical Papilla Cells to Root Dentin Surfaces Treated with Either 3Mix or Calcium Hydroxide. Journal of Endodontics. 2015;42(1):89-94. doi:10.1016/j.joen.2015.08.021
38) Nagata JY, Soares AJ, Souza-Filho FJ, et al. Microbial Evaluation of Traumatized Teeth Treated with Triple Antibiotic Paste or Calcium Hydroxide with 2% Chlorhexidine Gel in Pulp Revascularization. Journal of Endodontics. 2014;40(6):778-783. doi:10.1016/j.joen.2014.01.038
39) Grossman L. Antimicrobial effect of root canal cements. Journal of Endodontics. 1980;6(6):594-597. doi:10.1016/s0099-2399(80)80019-7
40) 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. International Endodontic Journal. 1996;29(2):125-130. doi:10.1111/j.1365-2591.1996.tb01173.x
41) 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. International Endodontic Journal. 1996;29(2):118-124. doi:10.1111/j.1365-2591.1996.tb01172.x
42) Nosrat A, Li KL, Vir K, Hicks ML, Fouad AF. Is pulp regeneration necessary for root maturation? Journal of Endodontics. 2013;39(10):1291-1295. doi:10.1016/j.joen.2013.06.019
43) Baumgartner J, Xia T. Antibiotic Susceptibility of Bacteria Associated with Endodontic Abscesses. Journal of Endodontics. 2003;29(1):44-47. doi:10.1097/00004770-200301000-00012
44) Sharma S, Bhushan U, Goswami M, Baveja C. Comparative evaluation of two antibiotic pastes for root canal disinfection. International Journal of Clinical Pediatric Dentistry. 2022;15(S1):S12-S17. doi:10.5005/jp-journals-10005-1898
45) Baziar M, Mehrasebi MR, Assadi A, Fazli MM, Maroosi M, Rahimi F. Erratum to: Efficiency of non-ionic surfactants - EDTA for treating TPH and heavy metals from contaminated soil. Journal of Environmental Health Science and Engineering. 2014;12(1). doi:10.1186/2052-336x-12-47
46) Galler KM, D’Souza RN, Federlin M, et al. Dentin Conditioning codetermines cell fate in regenerative endodontics. Journal of Endodontics. 2011;37(11): 1536-1541. doi:10.1016/j.joen.2011.08.027
47) Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB. Challenges in Regenerative Endodontics: a case series. Journal of Endodontics. 2009;36(3):536-541. doi:10.1016/j.joen.2009.10.006
48) Nosrat A, Homayounfar N, Oloomi K. Drawbacks and unfavorable outcomes of regenerative endodontic treatments of necrotic immature teeth: a literature review and report of a case. Journal of Endodontics. 2012;38(10):1428-1434. doi:10.1016/j.joen.2012.06.025
49) Caviedes‐Bucheli J, Muñoz‐Alvear HD, Lopez‐Moncayo LF, et al. Use of scaffolds and regenerative materials for the treatment of immature necrotic permanent teeth with periapical lesion: Umbrella review. International Endodontic Journal. 2022;55 (10):967-988. doi:10.1111/iej.13799
50) Torabinejad M, Turman M. Revitalization of Tooth with Necrotic Pulp and Open Apex by Using Platelet-rich Plasma: A Case Report. Journal of Endodontics. 2011;37(2):265-268. doi:10.1016/j.joen.2010.11.004
51) Jadhav G, Shah N, Logani A. Revascularization with and without Platelet-rich Plasma in Nonvital, Immature, Anterior Teeth: A Pilot Clinical Study. Journal of Endodontics. 2012;38(12):1581-1587. doi:10.1016/j.joen.2012.09.010
52) Bezgin T, Yilmaz AD, Celik BN, Kolsuz ME, Sonmez H. Efficacy of platelet-rich plasma as a scaffold in regenerative endodontic treatment. Journal of Endodontics. 2014;41(1):36-44. doi:10.1016/j.joen.2014.10.004
53) Bakhtiar H, Esmaeili S, Tabatabayi SF, Ellini MR, Nekoofar MH, Dummer PMH. Second-generation platelet concentrate (Platelet-rich fibrin) as a scaffold in regenerative endodontics: a case series. Journal of Endodontics. 2017;43(3):401-408. doi:10.1016/j.joen.2016.10.016
54) Narang I, Mittal N, Mishra N. A comparative evaluation of the blood clot, platelet-rich plasma, and platelet-rich fibrin in regeneration of necrotic immature permanent teeth: A clinical study. Contemporary Clinical Dentistry. 2015;6(1):63. doi:10.4103/0976-237x.149294
55) Lolato A, Bucchi C, Taschieri S, Kabbaney AE, Del Fabbro M. Platelet concentrates for revitalization of immature necrotic teeth: a systematic review of the clinical studies. Platelets. 2016;27(5):383-392. doi:10.3109/09537104.2015.1131255
56) Zhou R, Wang Y, Chen Y, et al. Radiographic, Histologic, and Biomechanical Evaluation of Combined Application of Platelet-rich Fibrin with Blood Clot in Regenerative Endodontics. Journal of Endodontics. 2017;43(12):2034-2040. doi:10.1016/j.joen.2017.07.021
57) Aksel H, Serper A: Recent considerations in regenerative endodontic treatment approaches . J Dent. 2014, 9:1-7. 10.1016/j.jds.2013.12.007
58) Antunes LS, Salles AG, Gomes CC, Andrade TB, Delmindo MP, Antunes L a. A. The effectiveness of pulp revascularization in root formation of necrotic immature permanent teeth: A systematic review. Acta Odontologica Scandinavica. 2015;74(3):161-169. doi:10.3109/00016357.2015.1069394
59) Tong HJ, Rajan S, Bhujel N, Kang J, Duggal M, Nazzal H. Regenerative Endodontic Therapy in the Management of Nonvital Immature Permanent Teeth: A Systematic Review—Outcome Evaluation and Meta-analysis. Journal of Endodontics. 2017;43(9):14 53-1464. doi:10.1016/j.joen.2017.04.018
60) Torabinejad M, Nosrat A, Verma P, Udochukwu O. Regenerative Endodontic Treatment or Mineral Trioxide Aggregate Apical Plug in Teeth with Necrotic Pulps and Open Apices: A Systematic Review and Meta-analysis. Journal of Endodontics. 2017;43(11):1806-1820. doi:10.1016/j.joen.2017.06.029
61) Alghamdi F, Alsulaimani M. Regenerative endodontic treatment: A systematic review of successful clinical cases. Dental and Medical Problems. 2021;58(4):555-567. doi:10.17219/dmp/132181
62) Kahler B, Mistry S, Moule A, et al. Revascularization outcomes: A prospective analysis of 16 consecutive cases. Journal of Endodontics. 2013;40(3):333-338. doi:10.1016/j.joen.2013.10.032
63) Alobaid AS, Cortes LM, Lo J, et al. Radiographic and clinical outcomes of the treatment of immature permanent teeth by revascularization or apexification: a pilot retrospective cohort study. Journal of Endodontics. 2014;40(8):1063-1070. doi:10.1016/j.joen.2014.02.016
64) Saoud TMA, Zaazou A, Nabil A, Moussa S, Lin LM, Gibbs JL. Clinical and Radiographic Outcomes of Traumatized Immature Permanent Necrotic Teeth after Revascularization/Revitalization Therapy. Journal of Endodontics. 2014;40(12):1946-1952. doi:10.1016/j.joen.2014.08.023
65) Li L, Pan Y, Mei L, Li J. Clinical and Radiographic Outcomes in Immature Permanent Necrotic Evaginated Teeth Treated with Regenerative Endodontic Procedures. Journal of Endodontics. 2016; 43(2):246-251. doi:10.1016/j.joen.2016.10.015
66) Nageh M, Ahmed GM, El-Baz AA. Assessment of Regaining Pulp Sensibility in Mature Necrotic Teeth Using a Modified Revascularization Technique with Platelet-rich Fibrin: A Clinical Study. Journal of Endodontics. 2018;44(10):1526-1533. doi:10.1016/j.joen.2018.06.014
67) Parirokh M, Torabinejad M. Mineral Trioxide Aggregate: A Comprehensive Literature Review—Part III: Clinical Applications, Drawbacks, and Mechanism of Action. Journal of Endodontics. 2010;36(3):400-413. doi:10.1016/j.joen.2009.09.009
68) Marconyak LJ, Kirkpatrick TC, Roberts HW, et al. A comparison of coronal tooth discoloration elicited by various endodontic reparative materials. Journal of Endodontics. 2015;42(3):470-473. doi:10.1016/j.joen.2015.10.013
69) Shokouhinejad N, Nekoofar MH, Pirmoazen S, Shamshiri AR, Dummer PMH. Evaluation and Comparison of Occurrence of Tooth Discoloration after the Application of Various Calcium Silicate–based Cements: An Ex Vivo Study. Journal of Endodontics. 2015;42(1):140-144. doi:10.1016/j.joen.2015.08.034
70) Kirchhoff AL, Raldi DP, Salles AC, Cunha RS, Mello I. Tooth discolouration and internal bleaching after the use of triple antibiotic paste. International Endodontic Journal. 2014;48(12):1181-1187. doi:10.1111/iej.12423
71) Thibodeau B, Teixeira F, Yamauchi M, Caplan DJ, Trope M. Pulp revascularization of immature dog teeth with apical periodontitis. Journal of Endodontics. 2007;33(6):680-689. doi:10.1016/j.joen.2007.03.001
72) Yamauchi N, Yamauchi S, Nagaoka H, et al. Tissue Engineering Strategies for Immature Teeth with Apical Periodontitis. Journal of Endodontics. 2011;37(3):390-397. doi:10.1016/j.joen.2010.11.010
73) Arslan H, Şahin Y, Topçuoğlu HS, Gündoğdu B. Histologic Evaluation of Regenerated Tissues in the Pulp Spaces of Teeth with Mature Roots at the Time of the Regenerative Endodontic Procedures. Journal of Endodontics. 2019;45(11):1384-1389. doi:10.1016/j.joen.2019.07.016
74) Topçuoğlu G, Topçuoğlu HS. Regenerative endodontic therapy in a single visit using platelet-rich plasma and biodentine in necrotic and asymptomatic immature molar teeth: a report of 3 cases. Journal of Endodontics. 2016;42(9):1344-1346. doi:10.1016/j.joen.2016.06.005
75) Chaniotis A. The use of a single‐step regenerative approach for the treatment of a replanted mandibular central incisor with severe resorption. International Endodontic Journal. 2015;49(8):802-812. doi:10.1111/iej.12515
76) Nassar MA, Roshdy NN, Kataia M, Mousa H, Sabet N. Assessment of the Clinical Outcomes of Single Visit Regenerative Endodontic Procedure In Treating Necrotic Mature Teeth with Apical Periodontitis Using Biological Irrigating Solution. Open Access Macedonian Journal of Medical Sciences. 2023;11(D): 61-64. doi:10.3889/oamjms.2023.11314
77) McCabe P. Revascularization of an immature tooth with apical periodontitis using a single visit protocol: a case report. International Endodontic Journal. 2014;48(5):484-497. doi:10.1111/iej.12344
78) Conde MCM, 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. International Endodontic Journal. 2016;50(9):860-874. doi:10.1111/iej.12711
79) Song M, Cao Y, Shin SJ, et al. Revascularization-associated intracanal calcification: Assessment of prevalence and contributing factors. Journal of Endodontics. 2017;43(12):2025-2033. doi:10.1016/j.joen.2017.06.018
80) Silujjai J, Linsuwanont P. Treatment Outcomes of apexification or revascularization in nonvital immature permanent teeth: a retrospective study. Journal of Endodontics. 2017;43(2):238-245. doi:10.1016/j.joen.2016.10.030
81) Lin J, Zeng Q, Wei X, et al. Regenerative Endodontics Versus Apexification in Immature Permanent Teeth with Apical Periodontitis: A Prospective Randomized Controlled Study. Journal of Endodontics. 2017;43(11):1821-1827. doi:10.1016/j.joen.2017.06.023
82) 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. Journal of Endodontics. 2009;35(10):1343-1349. doi:10.1016/j.joen.2009.06.021
83) De Toubes KMS, De Oliveira PAD, Machado SN, Pelosi V, Nunes E, Silveira FF. Clinical Approach to Pulp Canal Obliteration: A case series. PubMed. 2017;12(4):527-533. doi:10.22037/iej.v12i4.18006
84) Žižka R, Buchta T, Voborná I, Harvan L, Šedý J. Root maturation in teeth treated by unsuccessful revitalization: 2 case reports. Journal of Endodontics. 2016;42(5):724-729. doi:10.1016/j.joen.2016.02.004
85) Chaniotis A. Treatment options for failing regenerative endodontic procedures: Report of 3 cases. Journal of Endodontics. 2017;43(9):1472-1478. doi:10.1016/j.joen.2017.04.015
86) Keinan D, Nuni E, Rainus MB, Simhon TB, Dakar A, Slutzky-Goldberg I. Retreatment of failed regenerative Endodontic therapy: outcome and treatment considerations. Cureus. December 2024. doi:10.7759/cureus.75147