Rejeneratif Endodonti: Biyolojik Temeller, Klinik Protokoller ve Güncel Yaklaşımlar
Özet
Rejeneratif endodonti, nekrotik pulpalı dişlerde yalnızca enfeksiyonun ortadan kaldırılmasını değil, aynı zamanda pulpa-dentin kompleksinin biyolojik olarak yeniden oluşumunu hedefleyen modern bir tedavi yaklaşımıdır. Özellikle kök gelişimi tamamlanmamış dişlerde pulpa nekrozu geliştiğinde, geleneksel tedaviler apikal kapanmayı sağlasa da kök gelişiminin devamını mümkün kılmamaktadır. Bu durum, dentin duvarlarının ince kalmasına ve dişin kırılma riskinin artmasına neden olmaktadır. Rejeneratif endodontik tedaviler ise kök gelişiminin sürdürülmesini hedefleyerek dişin yapısal bütünlüğünü ve uzun dönem fonksiyonunu korumayı amaçlamaktadır. Bu tedaviler, doku mühendisliğinin temel bileşenleri olan kök hücreler, büyüme faktörleri ve iskelet yapılar arasındaki etkileşime dayanmaktadır. Klinik uygulamalarda minimal invaziv protokoller kullanılarak kanal dezenfeksiyonu sağlanmakta ve ardından biyolojik bir iskelet yapı oluşturularak kök hücrelerin kanal içerisine göçü teşvik edilmektedir. Başarı, yalnızca semptomların ortadan kalkması ile değil, aynı zamanda periapikal iyileşme, kök uzunluğunda artış ve dentin duvarlarının kalınlaşması gibi yapısal değişikliklerle değerlendirilmektedir. Bununla birlikte, renklenme, kanal obliterasyonu ve oluşan dokunun histolojik yapısına ilişkin belirsizlikler gibi bazı komplikasyonlar da bildirilmiştir. Son yıllarda kök hücre biyolojisi, biyomateryaller ve doku mühendisliği alanındaki gelişmeler, rejeneratif endodontinin kapsamını genişletmiştir. Hücre transplantasyonu, biyomimetik iskelet yapılar ve üç boyutlu biyobaskı gibi yenilikçi yaklaşımlar, gelecekte fonksiyonel pulpa dokusunun yeniden oluşturulmasına olanak sağlayabilecek potansiyel tedavi seçenekleri arasında yer almaktadır. Bu gelişmeler, rejeneratif endodontinin hem klinik uygulamalarda hem de araştırma alanında öneminin giderek artacağını göstermektedir.
Referanslar
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
Huang GT-J. A paradigm shift in endodontic management of immature teeth: conservation of stem cells for regeneration. Journal of Dentistry. 2008;36(6):379–386. doi:10.1016/j.jdent.2008.02.002
Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: biological basis of regenerative endodontic procedures. Pediatric Dentistry. 2013;35(2):129–140.
Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a root canal dressing may increase risk of root fracture. Dental Traumatology. 2002;18(3):134–137. doi:10.1034/j.1600-9657.2002.00097.x
Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha: a retrospective clinical study. Dental Traumatology. 1992;8(2):45–55. doi:10.1111/j.1600-9657.1992.tb00228.x
Frank AL. Therapy for the divergent pulpless tooth by continued apical formation. The Journal of the American Dental Association. 1966;72(1):87–93. doi:10.14219/jada.archive.1966.0038
Andreasen JO, Munksgaard EC, Bakland LK. Comparison of fracture resistance in root canals of immature sheep teeth after filling with calcium hydroxide or MTA. Dental Traumatology. 2006;22(3):154–156. doi:10.1111/j.1600-9657.2006.00419.x
Witherspoon DE. Vital pulp therapy with new materials: new directions and treatment perspectives—permanent teeth. Pediatric Dentistry. 2008;30(3):220–224.
American Association of Endodontists. AAE clinical considerations for a regenerative procedure. Chicago: American Association of Endodontists; 2016.
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
Vacanti JP, Langer R. Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. The Lancet. 1999;354:S32–S34. doi:10.1016/S0140-6736(99)90247-7
Curtis A, Riehle M. Tissue engineering: the biophysical background. Physics in Medicine and Biology. 2001;46(4):R47–R65. doi:10.1088/0031-9155/46/4/201
Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? Journal of Endodontics. 2004;30(4):196–200. doi:10.1097/00004770-200404000-00003
Galler KM, D’Souza RN, Hartgerink JD, Schmalz G. Scaffolds for dental pulp tissue engineering. Advances in Dental Research. 2011;23(3):333–339. doi:10.1177/0022034511405326
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. Journal of Endodontics. 2011;37(2):133–138. doi:10.1016/j.joen.2010.10.009
Sonoyama W, Liu Y, Yamaza T, et al. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. Journal of Endodontics. 2008;34(2):166–171. doi:10.1016/j.joen.2007.11.021
Sonoyama W, Liu Y, Fang D, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One. 2006;1(1):e79. doi:10.1371/journal.pone.0000079
Gronthos S, Mankani M, Brahim J, et al. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(25):13625–13630. doi:10.1073/pnas.240309797
Iohara K, Zheng L, Ito M, et al. Regeneration of dental pulp after pulpotomy by transplantation of CD31-/CD146-side population cells from a canine tooth. Regenerative Medicine. 2009;4(3):377–385. doi:10.2217/rme.09.17
Miura M, Gronthos S, Zhao M, et al. SHED: stem cells from human exfoliated deciduous teeth. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(10):5807–5812. doi:10.1073/pnas.0937635100
Seo B-M, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. The Lancet. 2004;364(9429):149–155. doi:10.1016/S0140-6736(04)16627-0
Huang GT-J, Yamaza T, Shea LD, et al. Stem/progenitor cell–mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Engineering Part A. 2010;16(2):605–615. doi:10.1089/ten.tea.2009.0518
Smith AJ, Scheven BA, Takahashi Y, et al. Dentine as a bioactive extracellular matrix. Archives of Oral Biology. 2012;57(2):109–121. doi:10.1016/j.archoralbio.2011.07.008
Galler KM, Widbiller M, Buchalla W, et al. EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells. International Endodontic Journal. 2016;49(6):581–590. doi:10.1111/iej.12469
Roberts-Clark D, Smith AJ. Angiogenic growth factors in human dentine matrix. Archives of Oral Biology. 2000;45(11):1013–1016. doi:10.1016/S0003-9969(00)00061-0
Nakashima M, Reddi AH. The application of bone morphogenetic proteins to dental tissue engineering. Nature Biotechnology. 2003;21(9):1025–1032. doi:10.1038/nbt864
Zhang W, Walboomers XF, Shi S, et al. Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Engineering. 2006;12(10):2813–2823. doi:10.1089/ten.2006.12.2813
Marx RE. Platelet-rich plasma: evidence to support its use. Journal of Oral and Maxillofacial Surgery. 2004;62(4):489–496. doi:10.1016/j.joms.2003.12.003
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
Dohan Ehrenfest DM, Andia I, Zumstein MA, et al. Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles, Ligaments and Tendons Journal. 2014;4(1):3–9. doi:10.11138/mltj/2014.4.1.003
Rosa V, Della Bona A, Cavalcanti BN, Nör JE. Tissue engineering: from research to dental clinics. Dental Materials. 2012;28(4):341–348. doi:10.1016/j.dental.2012.01.009
Zanjad SR, Justin RM, Patil PN, et al. Comparison of fracture resistance of simulated immature teeth using four different commercially available apexification materials: an in vitro study. Indian Journal of Dental Research. 2023;34(1):75–79. doi:10.4103/ijdr.ijdr_656_21
Ruparel N, Ruparel F, Hargreaves K, Diogenes A. Effect of intracanal medicaments on stem cells from apical papilla. Journal of Endodontics. 2012;38(3):e25. doi:10.1016/j.joen.2011.12.048
Diogenes A, Ruparel NB. Regenerative endodontic procedures: clinical outcomes. Dental Clinics of North America. 2017;61(1):111–125. doi:10.1016/j.cden.2016.08.004
Jeeruphan T, Jantarat J, Yanpiset K, et al. Mahidol study 1: comparison of radiographic and survival outcomes of immature teeth treated with either regenerative endodontic or apexification methods: a retrospective study. Journal of Endodontics. 2012;38(10):1330–1336. doi:10.1016/j.joen.2012.06.028
Wang X, Thibodeau B, Trope M, 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. 2010;36(1):56–63. doi:10.1016/j.joen.2009.09.039
Kim J-H, Kim Y, Shin S-J, et al. Tooth discoloration of immature permanent incisor associated with triple antibiotic therapy: a case report. Journal of Endodontics. 2010;36(6):1086–1091. doi:10.1016/j.joen.2010.03.031
Krastl G, Allgayer N, Lenherr P, et al. Tooth discoloration induced by endodontic materials: a literature review. Dental Traumatology. 2013;29(1):2–7. doi:10.1111/j.1600-9657.2012.01140.x
Sheng K, Ding N, Zhao SM, et al. Outcome of regenerative endodontic procedures in delayed replanted immature permanent teeth with apical periodontitis: a retrospective study. International Journal of Paediatric Dentistry. 2025;35(3):540–550. doi:10.1111/ipd.13166
Widbiller M, Galler KM. Regenerative endodontics. In: Vital Pulp Treatment. 2024:185–200. doi:10.1007/978-3-031-40682-3_11
Athirasala A, Tahayeri A, Thrivikraman G, et al. A dentin-derived hydrogel bioink for 3D bioprinting of cell-laden scaffolds for regenerative dentistry. Biofabrication. 2018;10(2):024101. doi:10.1088/1758-5090/aa9d44
Referanslar
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
Huang GT-J. A paradigm shift in endodontic management of immature teeth: conservation of stem cells for regeneration. Journal of Dentistry. 2008;36(6):379–386. doi:10.1016/j.jdent.2008.02.002
Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: biological basis of regenerative endodontic procedures. Pediatric Dentistry. 2013;35(2):129–140.
Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a root canal dressing may increase risk of root fracture. Dental Traumatology. 2002;18(3):134–137. doi:10.1034/j.1600-9657.2002.00097.x
Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha: a retrospective clinical study. Dental Traumatology. 1992;8(2):45–55. doi:10.1111/j.1600-9657.1992.tb00228.x
Frank AL. Therapy for the divergent pulpless tooth by continued apical formation. The Journal of the American Dental Association. 1966;72(1):87–93. doi:10.14219/jada.archive.1966.0038
Andreasen JO, Munksgaard EC, Bakland LK. Comparison of fracture resistance in root canals of immature sheep teeth after filling with calcium hydroxide or MTA. Dental Traumatology. 2006;22(3):154–156. doi:10.1111/j.1600-9657.2006.00419.x
Witherspoon DE. Vital pulp therapy with new materials: new directions and treatment perspectives—permanent teeth. Pediatric Dentistry. 2008;30(3):220–224.
American Association of Endodontists. AAE clinical considerations for a regenerative procedure. Chicago: American Association of Endodontists; 2016.
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
Vacanti JP, Langer R. Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. The Lancet. 1999;354:S32–S34. doi:10.1016/S0140-6736(99)90247-7
Curtis A, Riehle M. Tissue engineering: the biophysical background. Physics in Medicine and Biology. 2001;46(4):R47–R65. doi:10.1088/0031-9155/46/4/201
Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? Journal of Endodontics. 2004;30(4):196–200. doi:10.1097/00004770-200404000-00003
Galler KM, D’Souza RN, Hartgerink JD, Schmalz G. Scaffolds for dental pulp tissue engineering. Advances in Dental Research. 2011;23(3):333–339. doi:10.1177/0022034511405326
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. Journal of Endodontics. 2011;37(2):133–138. doi:10.1016/j.joen.2010.10.009
Sonoyama W, Liu Y, Yamaza T, et al. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. Journal of Endodontics. 2008;34(2):166–171. doi:10.1016/j.joen.2007.11.021
Sonoyama W, Liu Y, Fang D, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One. 2006;1(1):e79. doi:10.1371/journal.pone.0000079
Gronthos S, Mankani M, Brahim J, et al. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(25):13625–13630. doi:10.1073/pnas.240309797
Iohara K, Zheng L, Ito M, et al. Regeneration of dental pulp after pulpotomy by transplantation of CD31-/CD146-side population cells from a canine tooth. Regenerative Medicine. 2009;4(3):377–385. doi:10.2217/rme.09.17
Miura M, Gronthos S, Zhao M, et al. SHED: stem cells from human exfoliated deciduous teeth. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(10):5807–5812. doi:10.1073/pnas.0937635100
Seo B-M, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. The Lancet. 2004;364(9429):149–155. doi:10.1016/S0140-6736(04)16627-0
Huang GT-J, Yamaza T, Shea LD, et al. Stem/progenitor cell–mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Engineering Part A. 2010;16(2):605–615. doi:10.1089/ten.tea.2009.0518
Smith AJ, Scheven BA, Takahashi Y, et al. Dentine as a bioactive extracellular matrix. Archives of Oral Biology. 2012;57(2):109–121. doi:10.1016/j.archoralbio.2011.07.008
Galler KM, Widbiller M, Buchalla W, et al. EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells. International Endodontic Journal. 2016;49(6):581–590. doi:10.1111/iej.12469
Roberts-Clark D, Smith AJ. Angiogenic growth factors in human dentine matrix. Archives of Oral Biology. 2000;45(11):1013–1016. doi:10.1016/S0003-9969(00)00061-0
Nakashima M, Reddi AH. The application of bone morphogenetic proteins to dental tissue engineering. Nature Biotechnology. 2003;21(9):1025–1032. doi:10.1038/nbt864
Zhang W, Walboomers XF, Shi S, et al. Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Engineering. 2006;12(10):2813–2823. doi:10.1089/ten.2006.12.2813
Marx RE. Platelet-rich plasma: evidence to support its use. Journal of Oral and Maxillofacial Surgery. 2004;62(4):489–496. doi:10.1016/j.joms.2003.12.003
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
Dohan Ehrenfest DM, Andia I, Zumstein MA, et al. Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles, Ligaments and Tendons Journal. 2014;4(1):3–9. doi:10.11138/mltj/2014.4.1.003
Rosa V, Della Bona A, Cavalcanti BN, Nör JE. Tissue engineering: from research to dental clinics. Dental Materials. 2012;28(4):341–348. doi:10.1016/j.dental.2012.01.009
Zanjad SR, Justin RM, Patil PN, et al. Comparison of fracture resistance of simulated immature teeth using four different commercially available apexification materials: an in vitro study. Indian Journal of Dental Research. 2023;34(1):75–79. doi:10.4103/ijdr.ijdr_656_21
Ruparel N, Ruparel F, Hargreaves K, Diogenes A. Effect of intracanal medicaments on stem cells from apical papilla. Journal of Endodontics. 2012;38(3):e25. doi:10.1016/j.joen.2011.12.048
Diogenes A, Ruparel NB. Regenerative endodontic procedures: clinical outcomes. Dental Clinics of North America. 2017;61(1):111–125. doi:10.1016/j.cden.2016.08.004
Jeeruphan T, Jantarat J, Yanpiset K, et al. Mahidol study 1: comparison of radiographic and survival outcomes of immature teeth treated with either regenerative endodontic or apexification methods: a retrospective study. Journal of Endodontics. 2012;38(10):1330–1336. doi:10.1016/j.joen.2012.06.028
Wang X, Thibodeau B, Trope M, 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. 2010;36(1):56–63. doi:10.1016/j.joen.2009.09.039
Kim J-H, Kim Y, Shin S-J, et al. Tooth discoloration of immature permanent incisor associated with triple antibiotic therapy: a case report. Journal of Endodontics. 2010;36(6):1086–1091. doi:10.1016/j.joen.2010.03.031
Krastl G, Allgayer N, Lenherr P, et al. Tooth discoloration induced by endodontic materials: a literature review. Dental Traumatology. 2013;29(1):2–7. doi:10.1111/j.1600-9657.2012.01140.x
Sheng K, Ding N, Zhao SM, et al. Outcome of regenerative endodontic procedures in delayed replanted immature permanent teeth with apical periodontitis: a retrospective study. International Journal of Paediatric Dentistry. 2025;35(3):540–550. doi:10.1111/ipd.13166
Widbiller M, Galler KM. Regenerative endodontics. In: Vital Pulp Treatment. 2024:185–200. doi:10.1007/978-3-031-40682-3_11
Athirasala A, Tahayeri A, Thrivikraman G, et al. A dentin-derived hydrogel bioink for 3D bioprinting of cell-laden scaffolds for regenerative dentistry. Biofabrication. 2018;10(2):024101. doi:10.1088/1758-5090/aa9d44
