REGENERATIVE ENDODONTIC TREATMENTS PERFORMED ON IMMATURE PERMANENT TEETH

Year 2025, Volume: 11 Issue: 2, 179 - 191, 31.08.2025

Ayşe Süeda Genç , Simin Kocaaydın

Abstract

Immature permanent teeth may lose their vitality during their development due to trauma, caries or developmental anomalies. When pulp vitality is lost, root development stops, resulting in open apexed teeth with thin root dentin walls, making the treatment difficult. The endodontic treatment of immature and non-vital teeth is a challenging procedure for pediatric dentists and requires technical sensitivity. Additionally, the risk of root fracture increases due to weak tooth structure. Apexification is a non-surgical method that allows endodontic treatment to be performed by creating a calcific barrier in non-vital immature teeth. However, apexification treatments with both Ca(OH)₂ and MTA fail to thicken thin dentin walls and increase root length. Additionally, while apexification can induce apical closure, it cannot maintain pulp vitality. Nowadays, regenerative endodontic treatment procedure has been suggested to replace the damaged pulp tissue with pulp-like viable tissue. Regenerative procedures are biologically based treatments for the treatment of the dentin, root and dentin-pulp complex of the tooth. The aim of these treatments is to alleviate clinical symptoms in non-vital immature permanent teeth, heal apical lesions, increase the thickness of root walls, and promote continued root development. Thus, these teeth can have a more durable structure. Therefore, regenerative procedures have gained importance as an alternative treatment approach for teeth with open apices. The aim of this review is to examine the current information on regenerative endodontic treatments applied in non-vital immature permanent teeth as well as studies conducted in this field utilizing different biological factors based on tissue engineering principles.

Keywords

apexogenesis , open apex , regenerative endodontics

İmmatür Daimi Dişlerde Uygulanan Rejeneratif Endodontik Tedaviler

Abstract

İmmatür daimi dişler, gelişimleri esnasında travma, çürük veya gelişimsel anomaliler sebebiyle vitalitelerini kaybedebilmektedir. Pulpa vitalitesini kaybetmiş dişlerin kök gelişiminin durması ile, apikal gelişim sekteye uğramakta ve kök dentin duvarları yeterli kalınlığa ulaşamamaktadır. Çocuk diş hekimleri için zorlu bir prosedür olan immatür ve devital dişlerin endodontik tedavisi, teknik açıdan hassasiyet gerektirmektedir. Ayrıca ilerleyen zamanlarda zayıf diş dokusu sebebi ile kök kırığı riski artmaktadır. Apeksifikasyon, vital olmayan immatür dişlerde kök ucunda kalsifik bir bariyer oluşturarak endodontik tedavinin yapılmasını sağlayan ve cerrahi olmayan bir yöntemdir. Ancak hem Ca(OH)₂ hem de MTA ile yapılan apeksifikasyon tedavileri, ince dentin duvarlarının kalınlaşmasını ve kök uzunluğunda artışı sağlayamamaktadır. Bununla birlikte, apeksifikasyon apikal kapanmayı indükleyebilirken, pulpa canlılığını koruyamamaktadır. Günümüzde, hasarlı pulpa dokusunun sağlıklı pulpa benzeri doku ile değiştirilmesini amaçlayan rejeneratif endodontik tedavi prosedürü önerilmektedir. Rejeneratif prosedürler, dişin dentin, kök ve dentin-pulpa kompleksinin tedavisi için yapılan biyolojik temelli tedavilerdir. Bu tedavilerin amacı, devital immatür daimi dişlerde klinik semptomların giderilmesi, apikal lezyonun iyileşmesi, kök duvarlarının kalınlığının artması ve kök gelişiminin devam etmesini sağlamaktır. Böylelikle dişler daha dayanıklı bir yapıya sahip olabilmektedir. Bu nedenle, rejeneratif prosedürler açık apeksli immatür dişlerde alternatif ve güncel bir tedavi yaklaşımı olarak önem kazanmaktadır. Bu derlemenin amacı devital immatür daimi dişlerde uygulanan rejeneratif endodontik tedavilerin ve doku mühendisliği temelinde farklı biyolojik unsurlardan yararlanılarak bu alanda yapılan çalışmaların güncel bilgiler ışığında incelenmesidir.

Keywords

Açık apeks , apeksogenezis , rejeneratif endodonti

References

• Rafter M. Apexification: a review. Dent Traumatol. 2005;21(1):1-8. doi: 10.1111/j.1600- 9657.2004.00284.x.
• Koç S, Del Fabbro M. Does the Etiology of Pulp Necrosis Affect Regenerative Endodontic Treatment Outcomes? A Systematic Review and Meta-analyses. J Evid Based Dent Pract. 2020;20(1):101400. doi :10.1016/j.jebdp.2020.101400.
• Yang J, Zhao Y, Qin M, Ge L. Pulp revascularization of immature dens invaginatus with periapical periodontitis. J Endod. 2013;39(2):288-92. doi: 10.1016/j.joen.2012.10.017.
• Mukhopadhyay S, Ghosh C, Roy P, Paul T. Dens evaginatus in association with supernumerary teeth: Report of a case. Nigerian J Exp Clin Biosci. 2014;2(1):64-6. doi:10.4103/2348-0149.135733.
• Feigin K, Shope B. Regenerative Endodontics. J Vet Dent. 2017;34(3):161-78. doi:10.1177/0898756417722022.
• Alaçam A. “Kök ucu Kapanmamış Genç Sürekli Dişlerde Kök Gelişimi Teşviki ve Tedavi Yöntemleri,” In Endodonti, Ankara: Özyurt Matbaacılık, 2012, pp.1303-1332.
• 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(2):45-55. doi: 10.1111/j.1600-9657.1992.tb00228.x.
• Kim SG, Malek M, Sigurdsson A, Lin LM, Kahler B. Regenerative endodontics: a comprehensive review. Int Endod J. 2018;51(12):1367-88. doi: 10.1111/ iej.12954.
• Silujjai J, Linsuwanont P. Treatment Outcomes of Apexification or Revascularization in Nonvital Immature Permanent Teeth: A Retrospective Study. J Endod. 2017;43(2):238-45. doi: 10.1016/j. joen.2016.10.030.
• Andreasen JO, Pitt Ford TR. A radiographic study of the effect of various retrograde fillings on periapical healing after replantation. Endod Dent Traumatol. 1994;10(6):276-81. doi:10.1111/j.1600-9657.1994. tb00084.x.
• Mittmann CW, Kostka E, Ballout H, Preus M, Preissner R, Karaman M, Preissner S. Outcome of revascularization therapy in traumatized immature incisors. BMC Oral Health. 2020;20:207. doi:10.1186/ s12903-020-01193-5.
• J, Yang F, Li J, Hua F, He M, Song G. Treatment Outcomes of Regenerative Endodontic Procedures in Traumatized Immature Permanent Necrotic Teeth: A Retrospective Study. J Endod. 2022;48(9):1129-36. doi: 10.1016/j.joen.2022.03.015.
• Swaikat M, Faus-Matoses I, Zubizarreta-Macho Á, Ashkar I, Faus-Matoses V, Bellot-Arcís C, Iranzo- Cortés JE, Montiel-Company JM. Is Revascularization the Treatment of Choice for Traumatized Necrotic Immature Teeth? A Systematic Review and Meta- Analysis. J Clin Med. 2023;12(7):2656. doi: 10.3390/ jcm12072656.
• Sheehy EC, Roberts GJ. Use of calcium hydroxide for apical barrier formation and healing in non-vital immature permanent teeth: a review. Br Dent J. 1997;183(7):241-6. doi: 10.1038/sj.bdj.4809477.
• Lin JC, Lu JX, Zeng Q, Zhao W, Li WQ, Ling JQ. Comparison of mineral trioxide aggregate and calcium hydroxide for apexification of immature permanent teeth: A systematic review and metaanalysis. J Formos Med Assoc. 2016;115(7):523-30. doi: 10.1016/j.jfma.2016.01.010.
• Flanagan TA. What can cause the pulps of immature, permanent teeth with open apices to become necrotic and what treatment options are available for these teeth. Aust Endod J. 2014;40(3):95-100. doi: 10.1111/ aej.12087.
• Mohammadi Z, Dummer PMH. Properties and applications of calcium hydroxide in endodontics and dental traumatology. Int Endod J. 2011;44(8):697- 730. doi: 10.1111/j.1365-2591.2011.01886.x.
• Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a root canal dressing may increase risk of root fracture. Dent Traumatol. 2002;18(3):134- 7. doi:10.1034/j.1600-9657.2002.00097.x.
• Kumar A, Yadav A, Shetty N. One-step apexification using platelet rich fibrin matrix and mineral trioxide aggregate apical barrier. Indian J Dent Res. 2014;25(6):809-12. doi: 10.4103/0970-9290.152210.
• Moreno-Hidalgo MC, Caleza-Jimenez C, Mendoza- Mendoza A, Iglesias-Linares A. Revascularization of immature permanent teeth with apical periodontitis. Int Endod J. 2014;47(4):321-31. doi:10.1111/ iej.12154.
• Felippe WT, Felippe MCS, Rocha MJ. The effect of mineral trioxide aggregate on the apexification and periapical healing of teeth with incomplete root formation. Int Endod J. 2006;39(1):2-9. doi:10.1111/ j.1365-2591.2005.01037.x.
• American Association of Endodontists Special Committee on the Scope of Endodontics. AAE Position Statement: Scope of Endodontics: Regenerative Endodontics. 2013.
• AAE Clinical Considerations for a Regenerative Procedure Revised 5/18/2021.
• Perron GG, Kryazhimskiy S, Rice DP, Buckling A. Multidrug therapy and evolution of antibiotic resistance: when order matters. Appl Environ Microbiol. 2012;78(17):6137-42. doi:10.1128/ AEM.01078-12.
• Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: biological basis of regenerative endodontic procedures. J Endod. 2013;39(3 Suppl):S30-43. doi: 10.1016/j.joen.2012.
• Estefan BS, El Batouty KM, Nagy MM, Diogenes A. Influence of Age and Apical Diameter on the Success of Endodontic Regeneration Procedures. J Endod. 2016;42(11):1620-5. doi: 10.1016/j. joen.2016.06.020.
• Nakashima M, Iohara K. Mobilized dental pulp stem cells for pulp regeneration: initiation of clinical trial. J Endod. 2014;40(4 Suppl):S26-32. doi: 10.1016/j. joen.2014.01.020.
• Kellner M, Steindorff MM, Strempel JF, Winkel A, Kühnel MP, Stiesch M. Differences of isolated dental stem cells dependent on donor age and consequences for autologous tooth replacement. Arch Oral Biol. 2014;59(6):559-67. doi:10.4103/2348-0149.135733
• 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. J Endod. 2018;44(3):414- 31. doi: 10.1016/j.joen.2017.10.007.
• Wei X, Yang M, Yue L, Huang D, Zhou X, Wang X, et al. Expert consensus on regenerative endodontic procedures. Int J Oral Sci. 2022;14(1):55. doi: 10.1038/s41368-022-00206-z.
• Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dent Traumatol. 2001;17(4):185-7. doi: 10.1034/j.1600-9657.2001.017004185.x.
• Mittal N, Baranwal HC, Kumar P, Gupta S. Assessment of pulp sensibility in the mature necrotic teeth using regenerative endodontic therapy with various scaffolds-Randomised clinical trial. Indian J Dent Res. 2021;32(2):216-20. doi: 10.4103/ijdr. ijdr_253_21.
• Youssef A, Ali M, ElBolok A, Hassan R. Regenerative endodontic procedures for the treatment of necrotic mature teeth: A preliminary randomized clinical trial. Int Endod J. 2022;55(4):334-6. doi: 10.1111/ iej.13681.
• Chandki R, Kala M, Banthia P, Banthia R. From stem to roots: Tissue engineering in endodontics. J Clin Exp Dent. 2012;4(1):e66-71. doi: 10.4317/ jced.50678.
• Sedgley CM, Botero TM. Dental stem cells and their sources. Dent Clin North Am. 2012;56(3):549-61. doi: 10.1016/j.cden.2012.05.004.
• Orti V, Collart-Dutilleul PY, Piglionico S, Pall O, Cuisinier F, Panayotov I. Pulp Regeneration Concepts for Nonvital Teeth: From Tissue Engineering to Clinical Approaches. Tissue Eng Part B Rev. 2018;24(6):419-42. doi: 10.1089/ten.TEB.2018.0073.
• Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther. 2019;10(1):68. doi: 10.1186/s13287- 019-1165-5.
• Campanella V. Dental Stem Cells: Current research and future applications. Eur J Paediatr Dent. 2018;19(4):257. doi: 10.23804/ejpd.2018.19.04.1.
• Sakai K, Yamamoto A, Matsubara K, Nakamura S, Naruse M, Yamagata M, Sakamoto K, Tauchi R, Wakao N, Imagama S, Hibi H, Kadomatsu K, Ishiguro N, Ueda M. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Invest. 2012;122(1):80-90. doi: 10.1172/JCI59251.
• Kobayashi Y, Shimizu E. Current and Future Views on Cell-Homing-Based Strategies for Regenerative Endodontics. Clinical Approaches in Endodontic Regeneration. 2018:139-59. doi:10.1007/978-3-319-96848-3_8.
• Dissanayaka WL, Hargreaves KM, Jin L, Samaranayake LP, Zhang C. The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo. Tissue Eng Part A. 2015;21(3- 4):550-63. doi: 10.1089/ten.TEA.2014.0154.
• Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, Huang GT. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod. 2008;34(2):166-71. doi: 10.1016/j.joen.2007.11.021.
• Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P, Geurtsen W. Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Arch Oral Biol. 2011;56(7):709-21. doi: 10.1016/j. archoralbio.2010.12.008.
• Handa K, Saito M, Yamauchi M, Kiyono T, Sato S, Teranaka T, Sampath Narayanan A. Cementum matrix formation in vivo by cultured dental follicle cells. Bone. 2002;31(5):606-11. doi: 10.1016/s8756- 3282(02)00868-2.
• Isaka J, Ohazama A, Kobayashi M, Nagashima C, Takiguchi T, Kawasaki H, Tachikawa T, Hasegawa K. Participation of periodontal ligament cells with regeneration of alveolar bone. J Periodontol. 2001;72(3):314-23. doi: 10.1902/jop.2001.72.3.314.
• Wu Z, Dai W, Wang P, Zhang X, Tang Y, Liu L, Wang Q, Li M, Tang C. Periostin promotes migration, proliferation, and differentiation of human periodontal ligament mesenchymal stem cells. Connect Tissue Res. 2018;59(2):108-19. doi: 10.1080/03008207.2017.1306060.
• Abdallah BM, Kassem M. New factors controlling the balance between osteoblastogenesis and adipogenesis. Bone. 2012;50(2):540-5. doi: 10.1016/j. bone.2011.06.030.
• Ruangsawasdi N, Zehnder M, Patcas R, Ghayor C, Siegenthaler B, Gjoksi B, Weber FE. Effects of Stem Cell Factor on Cell Homing During Functional Pulp Regeneration in Human Immature Teeth. Tissue Eng Part A. 2017;23(3-4):115-23. doi: 10.1089/ten. TEA.2016.0227.
• Kim JK, Shukla R, Casagrande L, Sedgley C, Nör JE, Baker JR Jr, Hill EE. Differentiating dental pulp cells via RGD-dendrimer conjugates. J Dent Res. 2010;89(12):1433-8. doi: 10.1177/0022034510384870.
• Glynis A, Foschi F, Kefalou I, Koletsi D, Tzanetakis GN. Regenerative Endodontic Procedures for the Treatment of Necrotic Mature Teeth with Apical Periodontitis: A Systematic Review and Metaanalysis of Randomized Controlled Trials. J Endod. 2021;47(6):873-82. doi: 10.1016/j.joen.2021.03.015.
• Dianat O, Mashhadi Abas F, Paymanpour P, Eghbal MJ, Haddadpour S, Bahrololumi N. Endodontic repair in immature dogs’ teeth with apical periodontitis: blood clot vs plasma rich in growth factors scaffold. Dent Traumatol. 2017;33(2):84-90. doi: 10.1111/ edt.12306.
• 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. J Endod. 2012;38(10):1428- 34. doi: 10.1016/j.joen.2012.06.025.
• Dabbagh B, Alvaro E, Vu DD, Rizkallah J, Schwartz S. Clinical complications in the revascularization of immature necrotic permanent teeth. Pediatr Dent. 2012;34(5):414-7.
• Ogino Y, Ayukawa Y, Kukita T, Koyano K. The contribution of platelet-derived growth factor, transforming growth factor-beta1, and insulinlike growth factor-I in platelet-rich plasma to the proliferation of osteoblast-like cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(6):724- 9. doi: 10.1016/j.tripleo.2005.08.016.
• 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(5):745-9. doi: 10.1016/j.joen.2009.02.009.
• Slavkin HC, Bartold PM. Challenges and potential in tissue engineering. Periodontol 2000. 2006;41:9-15. doi: 10.1111/j.1600-0757.2006.00172.x.
• Franco D, Franco T, Schettino AM, Filho JM, Vendramin FS. Protocol for obtaining platelet-rich plasma (PRP), platelet-poor plasma (PPP), and thrombin for autologous use. Aesthetic Plast Surg. 2012;36(5):1254-9. doi: 10.1007/s00266-012-9957- 3.
• Kobayashi E, Flückiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B, Miron RJ. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig. 2016;20(9):2353-60. doi: 10.1007/s00784-016-1719- 1.
• Sabeti M, Ghobrial D, Zanjir M, da Costa BR, Young Y, Azarpazhooh A. Treatment outcomes of regenerative endodontic therapy in immature permanent teeth with pulpal necrosis: A systematic review and network meta-analysis. Int Endod J. 2024;57(3):238-55. doi: 10.1111/iej.13999.
• Murray PE. Platelet-Rich Plasma and Platelet- Rich Fibrin Can Induce Apical Closure More Frequently Than Blood-Clot Revascularization for the Regeneration of Immature Permanent Teeth: A Meta-Analysis of Clinical Efficacy. Front Bioeng Biotechnol. 2018;6:139. doi: 10.3389/ fbioe.2018.00139
• Shivashankar VY, Johns DA, Vidyanath S, Kumar MR. Platelet Rich Fibrin in the revitalization of tooth with necrotic pulp and open apex. J Conserv Dent. 2012;15(4):395-8. doi: 10.4103/0972-0707.101926.
• Zhou R, Wang Y, Chen Y, Chen S, Lyu H, Cai Z, Huang X. Radiographic, Histologic, and Biomechanical Evaluation of Combined Application of Platelet-rich Fibrin with Blood Clot in Regenerative Endodontics. J Endod. 2017;43(12):2034-40. doi: 10.1016/j. joen.2017.07.021.
• Li Z, Liu L, Wang L, Song D. The effects and potential applications of concentrated growth factor in dentinpulp complex regeneration. Stem Cell Res Ther. 2021;12(1):357. doi: 10.1186/s13287-021-02446-y.
• Honda H, Tamai N, Naka N, Yoshikawa H, Myoui A. Bone tissue engineering with bone marrow-derived stromal cells integrated with concentrated growth factor in Rattus norvegicus calvaria defect model. J Artif Organs. 2013;16(3):305-15. doi: 10.1007/ s10047-013-0711-7.
• Hong S, Li L, Cai W, Jiang B. The potential application of concentrated growth factor in regenerative endodontics. Int Endod J. 2019;52(5):646-55. doi: 10.1111/iej.13045.
• Lolato A, Bucchi C, Taschieri S, Kabbaney AE, Fabbro MD. Platelet concentrates for revitalization of immature necrotic teeth: a systematic review of the clinical studies. Platelets. 2016;27(5):383-92. doi: 10.3109/09537104.2015.1131255.
• Panda P, Mishra L, Govind S, Panda S, Lapinska B. Clinical Outcome and Comparison of Regenerative and Apexification Intervention in Young Immature Necrotic Teeth-A Systematic Review and Meta- Analysis. J Clin Med. 2022;11(13):3909. doi: 10.3390/jcm11133909.
• Panda S, Mishra L, Arbildo-Vega HI, Lapinska B, Lukomska-Szymanska M, Khijmatgar S, Parolia A, Bucchi C, Fabbro MD. Effectiveness of Autologous Platelet Concentrates in Management of Young Immature Necrotic Permanent Teeth-A Systematic Review and Meta-Analysis. Cells. 2020;9(10):2241. doi: 10.3390/cells9102241.
• Management of Non-Vital Permanent Teeth with Incomplete Root Formation. Available online: https:// ukdiss.com/examples/ non-vital-permanent-teethincomplete- root.php (accessed on 26 July 2021).
• Faizuddin U, Solomon RV, Mattapathi J, Guniganti SS. Revitalization of traumatized immature tooth with platelet-rich fibrin. Contemp Clin Dent. 2015;6(4):574-6. doi: 10.4103/0976-237X.169858.
• Nyberg E, Holmes C, Witham T, Grayson WL. Growth factor-eluting technologies for bone tissue engineering. Drug Deliv Transl Res. 2016;6(2):184- 94. doi: 10.1007/s13346-015-0233-3.
• Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16(5):585- 601. doi: 10.1111/j.1524-475X.2008.00410.x.
• Kim SG. Biological Molecules for the Regeneration of the Pulp-Dentin Complex. Dent Clin North Am. 2017;61(1):127-41. doi: 10.1016/j.cden.2016.08.005.
• Smith AJ, Scheven BA, Takahashi Y, Ferracane JL, Shelton RM, Cooper PR. Dentine as a bioactive extracellular matrix. Arch Oral Biol. 2012;57(2):109- 21. doi: 10.1016/j.archoralbio.2011.07.008.
• Galler KM, Buchalla W, Hiller KA, Federlin M, Eidt A, Schiefersteiner M, Schmalz G. Influence of root canal disinfectants on growth factor release from dentin. J Endod. 2015;41(3):363-8. doi: 10.1016/j. joen.2014.11.021.
• Lovelace TW, Henry MA, Hargreaves KM, Diogenes A. Evaluation of the delivery of mesenchymal stem cells into the root canal space of necrotic immature teeth after clinical regenerative endodontic procedure. J Endod. 2011;37(2):133-8. doi: 10.1016/j. joen.2010.10.009.
• Galler KM, Krastl G, Simon S, Van Gorp G, Meschi N, Vahedi B, Lambrechts P. European Society of Endodontology position statement: Revitalization procedures. Int Endod J. 2016;49(8):717-23. doi: 10.1111/iej.12629.
• Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB. Challenges in regenerative endodontics: a case series. J Endod. 2010;36(3):536- 41. doi: 10.1016/j.joen.2009.10.006.
• Kindelan SA, Day PF, Kindelan JD, Spencer JR, Duggal MS. Dental trauma: an overview of its influence on the management of orthodontic treatment. Part 1. J Orthod. 2008;35(2):68-78. doi: 10.1179/146531207225022482.
• 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. J Endod. 2017;43(11):1806-20. doi: 10.1016/j.joen.2017.06.029.
• Chrepa V, Joon R, Austah O, Diogenes A, Hargreaves KM, Ezeldeen M, Ruparel NB. Clinical Outcomes of Immature Teeth Treated with Regenerative Endodontic Procedures-A San Antonio Study. J Endod. 2020;46(8):1074-84. doi: 10.1016/j. joen.2020.04.008.
• Kontakiotis EG, Filippatos CG, Tzanetakis GN, Agrafioti A. Regenerative endodontic therapy: a data analysis of clinical protocols. J Endod. 2015;41(2):146-54. doi: 10.1016/j.joen.2014.08.003.
• Žižka R, Belák Š, Šedý J, Fačevicová K, Voborná I, Marinčák D. Clinical and Radiographic Outcomes of Immature Teeth Treated with Different Treatment Protocols of Regenerative Endodontic Procedures: A Retrospective Cohort Study. J Clin Med. 2021;10(8):1600. doi: 10.3390/jcm10081600.
• Martin DE, De Almeida JF, Henry MA, Khaing ZZ, Schmidt CE, Teixeira FB, Diogenes A. Concentrationdependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation. J Endod. 2014;40(1):51-5. doi: 10.1016/j.joen.2013.07.026.
• 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(10):1372-5. doi: 10.1016/j.joen.2012.06.018.
• Trevino EG, Patwardhan AN, Henry MA, Perry G, Dybdal-Hargreaves N, Hargreaves KM, Diogenes A. Effect of irrigants on the survival of human stem cells of the apical papilla in a platelet-rich plasma scaffold in human root tips. J Endod. 2011;37(8):1109-15. doi: 10.1016/j.joen.2011.05.013.
• Dos Reis-Prado AH, Abreu LG, Fagundes RR, Oliveira SC, Bottino MC, Ribeiro-Sobrinho AP, Benetti F. Influence of ethylenediaminetetraacetic acid on regenerative endodontics: A systematic review. Int Endod J. 2022;55(6):579-612. doi: 10.1111/iej.13728.
• Galler KM, Widbiller M, Buchalla W, Eidt A, Hiller KA, Hoffer PC, Schmalz G. EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells. Int Endod J. 2016;49(6):581-90. doi: 10.1111/iej.12492.
• Galler KM, D’Souza RN, Federlin M, Cavender AC, Hartgerink JD, Hecker S, Schmalz G. Dentin conditioning codetermines cell fate in regenerative endodontics. J Endod. 2011;37(11):1536-41. doi: 10.1016/j.joen.2011.08.027.
• Farhad Mollashahi N, Saberi E, Karkehabadi H. Evaluation of Cytotoxic Effects of Various Endodontic Irrigation Solutions on the Survival of Stem Cell of Human Apical Papilla. Iran Endod J. 2016;11(4):293- 7. doi: 10.22037/iej.2016.7.
• Lopes RMV, Marins FC, Belladonna FG, Souza EM, De-Deus G, Lopes RT, Silva EJNL. Untouched canal areas and debris accumulation after root canal preparation with rotary and adaptive systems. Aust Endod J. 2018;44(3):260-6. doi: 10.1111/aej.12237.
• Barnes GW, Langeland K. Antibody formation in primates following introduction of antigens into the root canal. J Dent Res. 1966;45(4):1111-4. doi: 10.1177/00220345660450041501.
• Malu K, Khubchandani M. Triple Antibiotic Paste: A Suitable Medicament for Intracanal Disinfection. Cureus. 2022;14(9):e29186. doi: 10.7759/ cureus.29186.
• Hoshino E, Kurihara-Ando N, Sato I, Uematsu H, Sato M, Kota K, Iwaku M. In-vitro antibacterial susceptibility of bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline. Int Endod J. 1996;29(2):125-30. doi: 10.1111/j.1365-2591.1996.tb01173.x.
• 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(2):118-24. doi: 10.1111/j.1365-2591.1996. tb01172.x.
• Akcay M, Arslan H, Yasa B, Kavrık F, Yasa E. Spectrophotometric analysis of crown discoloration induced by various antibiotic pastes used in revascularization. J Endod. 2014;40(6):845-8. doi: 10.1016/j.joen.2013.09.019.
• Montero-Miralles P, Martín-González J, Alonso- Ezpeleta O, Jiménez-Sánchez MC, Velasco-Ortega E, Segura-Egea JJ. Effectiveness and clinical implications of the use of topical antibiotics in regenerative endodontic procedures: a review. Int Endod J. 2018;51(9):981-8. doi: 10.1111/iej.12913.
• Makandar SD, Noorani TY. Triple antibiotic paste– Challenging intracanal medicament: A systematic review. Journal of International Oral Health. 2020;12(3):189-96. doi: 10.4103/jioh.jioh_213_19.
• Gharechahi M, Kafi MH, Javidi M, Jafari N, Joibary Moghaddam M. The Efficacy of Different Antibiotic Compounds in Regenerative Treatment of Immature Necrotic Teeth. Front Dent. 2024;21:1. doi: 10.18502/ fid.v21i1.14638.
• Kim JH, Kim Y, Shin SJ, Park JW, Jung IY. Tooth discoloration of immature permanent incisor associated with triple antibiotic therapy: a case report. J Endod. 2010;36(6):1086-91. doi: 10.1016/j. joen.2010.03.031.
• Mohammadi Z, Shalavi S. Is chlorhexidine an ideal vehicle for calcium hydroxide? A microbiologic review. Iran Endod J. 2012;7(3):115-22.
• Tagelsir A, Yassen GH, Gomez GF, Gregory RL. Effect of Antimicrobials Used in Regenerative Endodontic Procedures on 3-week-old Enterococcus faecalis Biofilm. J Endod. 2016;42(2):258-62. doi: 10.1016/j.joen.2015.09.023.
• Berkhoff JA, Chen PB, Teixeira FB, Diogenes A. Evaluation of triple antibiotic paste removal by different irrigation procedures. J Endod. 2014;40(8):1172-7. doi: 10.1016/j.joen.2013.12.027.
• 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(1):44-8. doi: 10.1046/j.0143- 2885.2003.00611.x.
• Torabinejad M, Watson TF, Pitt Ford TR. Sealing ability of a mineral trioxide aggregate when used as a root end filling material. J Endod. 1993;19(12):591- 5. doi: 10.1016/S0099-2399(06)80271-2.
• Arslan H, Ahmed HMA, Şahin Y, Doğanay Yıldız E, Gündoğdu EC, Güven Y, Khalilov R. Regenerative Endodontic Procedures in Necrotic Mature Teeth with Periapical Radiolucencies: A Preliminary Randomized Clinical Study. J Endod. 2019;45(7):863-72. doi: 10.1016/j.joen.2019.04.005.
• Luo Z, Li D, Kohli MR, Yu Q, Kim S, He WX. Effect of BiodentineTM on the proliferation, migration and adhesion of human dental pulp stem cells. J Dent. 2014;42(4):490-7. doi: 10.1016/j.jdent.2013.12.011.
• Subramanyam D, Vasantharajan M. Effect of Oral Tissue Fluids on Compressive Strength of MTA and Biodentine: An In vitro Study. J Clin Diagn Res. 2017;11(4):ZC94-6. doi: 10.7860/ JCDR/2017/24510.9722.
• Elnaghy AM, Elsaka SE. Fracture resistance of simulated immature teeth filled with Biodentine and white mineral trioxide aggregate-an in vitro study. Dent Traumatol. 2016;32(2):116-20. doi: 10.1111/ edt.12224.