Regenerative Endodontics

"Exploring Regenerative Endodontics: A Paradigm Shift in Root Canal Therapy" aims to delve into the groundbreaking approach of regenerative endodontics, which has revolutionized traditional root canal treatments. This presentation serves as a comprehensive guide for dental professionals, researchers, and students who are keen on understanding the shift towards biologically-based procedures designed to replace damaged tooth structures, including dentin and root structures, as well as cells of the pulp-dentin complex.

Key Points Covered:
Introduction to Traditional Endodontics: A brief overview of conventional root canal treatments, setting the stage for the limitations that regenerative endodontics aims to address.

Fundamentals of Regenerative Endodontics: Understand what regenerative endodontics is, its aims, and the principles guiding this new approach.

Materials and Techniques: Discover the novel materials and technologies used in regenerative endodontics including scaffolds, growth factors, and stem cells.

Clinical Applications and Benefits: Discuss various case studies and clinical trials that demonstrate the effectiveness and benefits of regenerative procedures.

Challenges and Future Prospects: A balanced view on the hurdles facing regenerative endodontics and what the future holds.

This presentation is essential viewing for anyone interested in the future of dental science and how regenerative approaches can offer effective and more natural alternatives to traditional endodontic treatments."

Feel free to modify this description to better suit your specific needs and focus points.

1. Introduction Concepts Triad of Tissue Engineering Environmental Influences on Regeneration Regenerative Endodontic Procedures Regenerative Strategies Root Canal Revascularization Pulp Implantation Clinical Procedure for Regenerative Endodontic Procedures Translational Studies Conclusion CONTENTS 2

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3. Tissue Engineering Restoring root canals + periodontium Introduction Healthy State Hope for retaining a natural dentition Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. 4

4. Definitions Regenerative endodontics are biologically based procedures designed to replace damaged structures, including dentin and root structures, as well as cells of the pulp– dentin complex. Revascularization , as defined by Andreasen , is the restoration of the vascularity to a tissue or organ. Repair is the restoration of tissue continuity without the loss of original architecture and function. Revitalization is described as an ingrowth of vital tissue that does not resemble the original lost tissue. Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. 5

5. Concepts Interdisciplinary field Engineering Life Sciences Development of biological substitutes Restore, maintain or improve tissue function or a whole organ follows principles of Tissue Engineering Langer & Vacanti Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. 6

6. Triad of Tissue Engineering Stem Cells Scaffolds Signaling Molecules Optimum time and environment Regenerated Tissue Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. 7

7. Stem Cells & Progenitor Cells Stem Cells Undifferentiated cells Can differentiate into various specialized cell types Regenerative endodontic procedures are stem cell based therapies (Diogenes et al) Multipotent Pluripotent - C an differentiate into a limited range of cell types within a particular tissue - Hematopoietic stem cells Can differentiate into any of the 3 germ layers Cannot form an entire organism Totipotent - Can differentiate into any cell type. - Cells from early embryos (1-3 days) - Eg : Zygote and the initial cells that arise from its first few divisions Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: biological basis of regenerative endodontic procedures. Pediatric dentistry. 2013 Apr 15;35(2):129-40. 8

8. Stem Cells / Progenitor Cells According to Source: Allogenic Cells Autologous Cells Xenogeneic Cells Isogenic Cells Obtained from same person Obtained from same species Obtained from different species Animal cells useful in cardiovascular implants Obtained from genetically identical organisms Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. 9

9. Stem Cell Niches Embryonic Development Migration of cranial neural crest cells to mesenchyme of first brachial arch Ecto -mesenchymal cells (dental papilla & dental follicle) Mature tooth contain various undifferentiated cells in pulp These cells contain mesenchymal-stem-cell like properties (MSC) Lyu P, Li B, Li P, Bi R, Cui C, Zhao Z, Zhou X, Fan Y. Parathyroid hormone 1 receptor signaling in dental mesenchymal stem cells: basic and clinical implications. Frontiers in Cell and Developmental Biology. 2021 Oct 25;9:654715. Dental Pulp Stem Cells were the first population of stem cells to be described 10

10. Stem Cell Niches Stem cells of the apical papilla (SCAP) 2. Dental pulp stem cells (DPSCs) 3. Inflamed periapical progenitor cells ( iPAPCs ) 4. Periodontal ligament stem cells (PDLSCs) 5. Bone marrow stem cells (BMSCs) According to Hargreaves Microenvironment for stem cells Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: biological basis of regenerative endodontic procedures. Pediatric dentistry. 2013 Apr 15;35(2):129-40. Maintains stem cells in quiescent stage 11

11. Growth Factors Biological Factors Stimulates differentiation of mesenchymal stem cells Odontoblast like cells Functions: To stimulate division of neighboring cells To stimulate the differentiation of certain cells along a specified pathway To stimulate Angiogenesis To serve as chemoattractant for specific cell types Also called – Signaling Molecules / Morphogens PGDF BMP Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. 12

12. Growth Factors Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. Mechanism: Recruitment of stem cells Cellular Proliferation Angiogenesis Matrix Deposition & Tissue Remodeling Cellular Differentiation Chemotactic agents Attraction to injury site IGF / PDGF Signals stem cell proliferation VEGF Stimulates formation of blood vessels BMP / TGF – β Signals stem cells to form into odontoblasts Dentin deposition starts MMP’s facilitate remodelling of new matrix 13

13. Growth Factors Also called – Signaling Molecules / Morphogens BMPs • Fibroblast growth factors (FGFs) • Tumour necrotic factor (TNF) • Transforming growth factor (TGF) • Insulin-like growth factor (IGF) • Epidermal growth factor (EGF) • Interleukins (IL) • PDGF • Nerve growth factor (NGF) Embryonic Tooth Development Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. 14

14. Scaffold 3D structure that contains growth factors. It has the following functions: Supports cell organization and vascularization Aids stem cell proliferation and differentiation Leads to improved and faster tissue development Contains nutrients to promote cell survival and growth May contain antibiotics to prevent bacterial ingrowth in the canal systems Mechanical and biological functions Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. 15

15. Scaffold CLASSIFICATION Natural Synthetic Collagen Platelet Rich Fibrin Glycosaminoglycan Polylactic Acid (PLA) Polyglycolic Acid (PGA) Polyethylene Glycol (PEG) Polycaprolactone (PCL) Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. 16

16. Scaffold 17 https://www.mdpi.com/2073-4360/15/5/1082#

17. Platelet Rich Fibrin “ Choukrouns PRF” 2001 – Dr. Joseph Choukroun et al introduced the concept of PRF in dentistry as a scaffold material What is PRF? A second generation autologous platelet concentrate suspended in a fibrin mesh Prepared by centrifuging patients own blood for a given time Acts as an excellent Scaffold in Regenerative Endodontic Procedures Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci. 2011 Jan;1:23-8. 18

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19. https://youtu.be/4z7uj4I5kCg?si=_OhtQMVUUr2ABBwi 20

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21. Platelet Rich Fibrin Types of PRF? Second Generation : L-PRF (Leukocyte- and Platelet-Rich Fibrin) Preparation : Centrifuged at a slow speed (around 2700 rpm for 12 minutes). Characteristics : Contains leukocytes, which may influence inflammation and immunity. Appearance : Yellow, dense fibrin clot with the red blood cells concentrated at the base. Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci. 2011 Jan;1:23-8. 22

22. Platelet Rich Fibrin Types of PRF? A-PRF (Advanced Platelet Rich Fibrin) Preparation: Reduced centrifugation speeds (around 1500 rpm for 14 minutes) Characteristics: Improved fibrin architecture, increased leukocyte and growth factor content Appearance: More porous, superior for cellular migration Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci. 2011 Jan;1:23-8. 23

23. Platelet Rich Fibrin Types of PRF? i -PRF (Injectable Platelet Rich Fibrin) Preparation : 1300 RPM for 8 minutes Characteristics : Fluid form of PRF; can be combined with other biomaterials Usage : Suitable for hard-to-reach areas or as an adjunct with bone graft materials Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci. 2011 Jan;1:23-8. 24

24. Platelet Rich Fibrin Types of PRF? S-PRF (Solid Platelet Rich Fibrin) Preparation : general protocol leans towards that of L-PRF or A-PRF Characteristics : Solid form, but with modifications to optimize the regenerative potential. Usage : Ideal for surgical sites requiring stabilization or protection. Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci. 2011 Jan;1:23-8. 25

25. Platelet Rich Fibrin Centrifugation Miron and colleagues Horizontal centrifugation better than fixed angle More concentration of platelets, leukocytes, and monocytes  Fixed angle centrifugation causes trapping of essential elements along with the sunk RBC’s in the back of the test tube https://bioprf.eu/bio-prf-science/ 26

26. Platelet Rich Fibrin Centrifugation https://bioprf.eu/bio-prf-science/ 27

27. Choukrouns Box / PRF Box (Process, Nice, France) Helps in draining excess exudate from the PRF clot Makes the PRF clot more manageable Compression plate helps in draining the PRF clot Production of an economical autologous fibrin membrane in approximately one minute Average Cost: 4000 - 5000 https://www.gdcdental.com/products-detail.php?id=1079 28

28. Environmental Influences on Regnerative events Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. Microbial penetration & defense responses: Micro-organisms and their by-products can penetrate dentin matrix and induce cellular responses in pulp Overtime the microbial load increases, leading to these micro-organisms being found in the pulp Role of Odontoblasts: Odontoblasts play a key role in environmental sensing & defense Odontoblasts have matrix secretory functions Their lateral processes makes up for an extensive network for facilitating communication within the dentin matrix 29

29. Environmental Influences on Regnerative events Microbial Sensing: Odontoblasts release antimicrobial peptides and various cytokines Micro-organisms are detected by Pattern Recognition Receptors (PRR) molecules, specifically Toll-Like-Receptors Intracellular Signalling : Microbial sensing activates intracellular signaling pathways like NF-kB, p-38 MAP Kinase, and JNK This results in release of inflammatory mediators, amplifying defense responses and recruiting immune cells Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 30

30. Environmental Influences on Regnerative events Pulpal environment during disease progression: Direct and Indirect inflammatory influences impact the pulpal environment Microbes and inflammation can degrade pulp molecular constituents, influencing their functions. Inflammatory/Immune Response-Regeneration Interplay: Mesenchymal stem cells (MSCs) can modulate the functions of various immune cells. Low levels of inflammation stimulate regenerative events, while higher levels impede them. Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 31

31. Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Regenerative Endodontic Procedures Regenerative endodontics is defined as biologically based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as pulp dentin complex. GOALS OF REGENERATIVE PROCEDURES 32

32. Regenerative Strategies Regenerative strategies in endodontics are dependent on stem cells, cellular scaffolds, and signalling molecules Cell Based Approach Cell Free Approach Avoiding the need to directly transplant cells to injury site Focuses on providing a conductive environment for regeneration Bioactive Molecules Chemical treatment of tissues Stem cell transfer from apical tissues Transplantation of cells to the site of injury in the tissue to promote regeneration Offers long term success rate Requires the use of cells of the highest good manufacturing practice (GMP) quality Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 33

33. Root Canal Revascularization Revascularization is the procedure to re-establish vitality in a non-vital tooth to allow repair and regeneration of tissue. It allows further development of root and dentin structure with a better long-term prognosis. Necrotic teeth with open apices Some vital pulp / Hertwig’s Epithelial Root Sheath Pulp proliferation once disinfected Apexification Why Revascularization? Calcium Hydroxide No continued root formation No thickening of root canal walls Risk of root fractures Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. 34

34. Root Canal Revascularization Indications ? Teeth presenting symptoms of chronic apical periodontitis Immature Apex / Blunderbuss canal Wide canal / Parallel walls Non – Vital on pulp sensibility tests Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. 35

35. Root Canal Revascularization Technique : First Appointment Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Metronidazole + Ciprofloxacin in Distilled Water 2mm from W.L. Closed Dressing Recall in 3-4 weeks 5.25% 36 P/L ratio – 2.5:1 Madhukumar M, Geetha P, Nair KR, Unnikrishnan M. The effects of double antibiotic paste and amoxicillin-clavulanate paste used in endodontic regeneration on microhardness of radicular dentine: an In vitro study. Journal of Pharmacy & Bioallied Sciences. 2021 Jun;13( Suppl 1):S510. Conc: 0.1mg/ml

36. Root Canal Revascularization Technique : Second Appointment Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. 5.25% Allow blood to reach 3mm below CEJ Leave for 15 mins 37

37. Root Canal Revascularization Technique : Second Appointment Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Scaffold Regeneration & Repair Place MTA over the clot and temporarily restore the tooth After 1 week – Restore tooth with composite Patients recalled after a minimum of 6 months -1 year 38

38. Criteria of Success Lack of symptoms Radiographic evidence of increased root length Radiographic evidence of increased root canal thickness Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. 39

39. Mechanism of Revascularization Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Few cells remain at the apical end of root canal Differentiate into odontoblasts under the organizing influence of Hertwig’s Epithelial Root Sheath Newly formed odontoblasts lay down Atubular Dentin Apexogenesis is favored Dentin deposition at the lateral aspects of the root canal wall 40

40. Mechanism of Revascularization Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. DPSC’s present at apical end, aid in Apexogenesis Might form Tertiary dentin at the lateral aspects of the dentinal wall Stem cells in the PDL also lay down hard tissue at apical end & lateral walls Root development attributed to the stem cells of apical papilla Inducing bleeding causes mesenchymal cells to enter canal and cause regeneration 41

41. Mechanism of Revascularization Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Blood clot is a scaffold reservoir Platelet derived growth factor Vascular Factor Tissue Growth Factor 42

42. Advantages of Revascularization Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Short treatment time – 1-2 visits In-expensive Strengthening of lateral root walls Autologous grafts crosses out immune rejection Obturation of root canal not necessary – less chances of root fracture 43

43. Disadvantages of Revascularization Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Composition of cells in fibrin clot unreliable - can result in variations in treatment Crown Discolouration Allergic reactions to intra-canal-medications Development of resistant bacterial strains Entire canal might get calcified resulting in compromised treatment 44

44. Post Natal Stem Cell Therapy Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Two kinds of stem cells according to their origin Embryonic Stem Cells Post Natal Stem Cells (Pluripotent) Can be isolated from normal blastocyst Will give rise to all derivatives of 3 layers Can be directly collected from umbilical cord blood or bone marrow Highly Plastic Less Plastic Limited Life Cycle 45

45. Stem Cells of Dental Origin Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Dental Pulp Stem Cells Periodontal Ligament Stem Cells Dental Follicle Precursor Cells Stem Cells from Apical Papilla 46

46. Stem Cells of Dental Origin Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Dental Pulp Stem Cells Origin and Potential : Dental Pulp / Wisdom teeth or shed primary teeth Mineralized matrix with tubules lined with odontoblasts and fibrous tissue containing blood vessels Multipotent Capable of inducing Dentinogenesis Regenerates other tissues like pulp / periodontal ligament 47

47. Stem Cells of Dental Origin Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Periodontal Ligament Stem Cells Harvested from enzymatically digested PDL Can regenerate cementum lined with collagen fibers similar to Sharpey’s fibers isolated PDLSCs Expanded Cultured Differentiation into different cell types 48

48. Stem Cells of Dental Origin Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. Stem Cells from Apical Papilla Origin : Apical papilla in the apices of developing teeth Multipotent Apical cell rich zone – between – Apical papilla & Pulp C an undergo odontoblastic, osteogenic, or neurogenic differentiation 49

49. Pulp Implantation Abbass MM, El- Rashidy AA, Sadek KM, Moshy SE, Radwan IA, Rady D, Dörfer CE, Fawzy El-Sayed KM. Hydrogels and dentin–pulp complex regeneration: from the benchtop to clinical translation. Polymers. 2020 Dec 9;12(12):2935. Replacement Pulp Therapy Hydrogel acts as Scaffold for DPSC’s DPSC’s can be loaded onto the polymeric sheets and placed into canals DMP-1 expression observed after 28 days 50

50. Case Report 7 year old – referred to private practice for evaluation of maxillary right central incisor Avulsion injury 3 days prior to visit Previous dentist irrigated tooth with CHX and reimplanted it Dentist stabilized tooth with stainless steel orthodontic wire and referred the patient Total Extra Oral Dry Time : 60 minutes Tenderness to percussion: Positive EPT/Cold Test: No Response Hung R, Torabinejad M. Regenerative Endodontic Procedure (REP) in single session with MTAD disinfection on immature avulsion tooth: 4-year control. J Dent Res.;2:1-4. 51

51. Case Report Pulpal Diagnosis: Necrotic Pulp Periapical Diagnosis: Symptomatic Apical Periodontitis Local Anaesthesia: Lidocaine 2% 1:100,000 epinephrine Isolation: Rubber Dam Working Length Determined using Apex Locator and Radiographic Method Light Instrumentation + irrigation with 10ml 5.25% NaOCl 5.25% Hung R, Torabinejad M. Regenerative Endodontic Procedure (REP) in single session with MTAD disinfection on immature avulsion tooth: 4-year control. J Dent Res.;2:1-4. 52

52. Case Report 1ml of MTAD was placed for 5 mins Then rinsed with 4ml MTAD and dried Local Anaesthesia: Lidocaine 2% 1:100,000 epinephrine Bleeding was induced: pre bent size 25 K-file – 2mm beyond working length 3-4mm of MTA gently condensed over the clot Tooth restored with composite Hung R, Torabinejad M. Regenerative Endodontic Procedure (REP) in single session with MTAD disinfection on immature avulsion tooth: 4-year control. J Dent Res.;2:1-4. 53

53. Case Report Patient reported to clinic after 6 months Radiographically: root apex started closing Patient reported no pain / no symptoms After 1 year 6 months Apex completely closed After 2 years 6 months After 4 years Asymptomatic / positive to EPT & Cold test Hung R, Torabinejad M. Regenerative Endodontic Procedure (REP) in single session with MTAD disinfection on immature avulsion tooth: 4-year control. J Dent Res.;2:1-4. 54

54. 12 year old female Tooth involved : maxillary right central incisor History of trauma : lateral luxation injury 2 year ago Pulpal Diagnosis : Pulpal Necrosis Radiographic findings : Periapical Abscess w.r.t. 11, thinning of lateral walls of root canal Apical Diagnosis : Acute Apical Abscess Clinical Procedure for REP’s Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 55

55. Clinical Procedure for REP’s Access opening and working length determination is done Local Anaesthesia - 2% Lidocaine with 1:100,000 epinephrine Isolation done with Rubber Dam Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 56

56. Slow Irrigation done with 1.5% NaOCl (20ml/5 minutes) Canals dried with paper points Canals then rinsed with 17% EDTA (10ml/2 minutes) Double Antibiotic paste or Calcium Hydroxide placed in the canals (1mg/1ml) Canals dried with paper points Access sealed with GIC Patient recalled after 4 weeks Clinical Procedure for REP’s Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 57

57. Patient was asymptomatic, no swelling, no sinus tract Temporary restoration was removed Calcium hydroxide was removed with saline irrigation A size 25, precurved K-file was over-instrumented 2mm into the periapical area to induce bleeding Final rinse done with 17% EDTA 20ml for 5 minutes Canals are dried with paper points Local anaesthesia with 3% Mepivacaine Isolation done Clinical Procedure for REP’s Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 58

58. Collaplug ™ (Zimmer Dental Inc, Warsaw, Indiana, U.S.A) placed on top of the blood clot Cavity sealed with packable composite Patient revied at 3 months / 6 months / 1 year / 2 years, then annually for 5 years Serves as an internal matrix for a 3mm white MTA or Biodentine Light cured GIC flowed over the MTA/ Biodentine Clinical Procedure for REP’s Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 59

59. Case Report Hung R, Torabinejad M. Regenerative Endodontic Procedure (REP) in single session with MTAD disinfection on immature avulsion tooth: 4-year control. J Dent Res.;2:1-4. Dr. M. Torabinejad 60

60. Regeneration of Mature Permanent Teeth: Scope? Regenerative endodontic procedures in mature human teeth resulted in the formation of fibrous connective tissue containing bonelike tissue, vascular structures, and inflammation, which is similar to the findings in immature teeth. Regenerative endodontic procedures have the potential to be used as a treatment option for mature teeth with large periapical radiolucencies . 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 Nov 1;45(11):1384-9. Arslan H, Ahmed HM, Şahin Y, Yıldız ED, Gündoğdu EC, Güven Y, Khalilov R. Regenerative endodontic procedures in necrotic mature teeth with periapical radiolucencies : a preliminary randomized clinical study. Journal of endodontics. 2019 Jul 1;45(7):863-72. 61

61. Regeneration of Mature Permanent Teeth: Scope? This systematic review found that REPs effectively treat both mature and immature necrotic permanent teeth. Mature teeth showed better vitality responses than immature teeth with necrotic pulps. Murad M, Cooper PR. Regenerative endodontic procedures: are they more successful in mature permanent teeth with necrotic pulp than in immature teeth?. Evidence-Based Dentistry. 2023 Aug 4:1-2. 62

62. Advanced Scaffolds Collagen/Alginate Composite Scaffold developed Mimics the shape of gutta percha with great accuracy and reproducibility Stem cells seeded onto this scaffold differentiated into osteoblasts producing osseous extracellular matrix Devillard , R., Rémy, M., Kalisky , J., Bourget, J., Kérourédan , O., Siadous , R., Bareille , R., Amédée-Vilamitjana , J., Chassande , O., & Fricain , J. (2017). In vitro assessment of a collagen/alginate composite scaffold for regenerative endodontics. International Endodontic Journal, 50, 48–57. 63

63. C onclusion Endodontic regeneration represents a groundbreaking shift in the way we approach dental pulp diseases. Harnessing the body's innate ability to heal and regenerate, this method not only offers a biological solution to dental pathologies but also promises improved patient outcomes and long-term tooth viability. As technology and research continue to advance, the potential for endodontic regeneration will undoubtedly expand, further bridging the gap between traditional endodontics and the broader field of regenerative medicine. 64

64. R eferences Chandra S. Grossman’s endodontic practice. Wolters kluwer india Pvt Ltd; 2014. Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: biological basis of regenerative endodontic procedures. Pediatric dentistry. 2013 Apr 15;35(2):129-40. Garg N, Garg A. Textbook of endodontics. Boydell & Brewer Ltd; 2010 Nov 26. https://bioprf.eu/bio-prf-science/ Devillard , R., Rémy, M., Kalisky , J., Bourget, J., Kérourédan , O., Siadous , R., Bareille , R., Amédée-Vilamitjana , J., Chassande , O., & Fricain , J. (2017). In vitro assessment of a collagen/alginate composite scaffold for regenerative endodontics. International Endodontic Journal, 50, 48–57. Rotstein I, Ingle JI, editors. Ingle's endodontics. PMPH USA; 2019 Jun 1. 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 Nov 1;45(11):1384-9. Arslan H, Ahmed HM, Şahin Y, Yıldız ED, Gündoğdu EC, Güven Y, Khalilov R. Regenerative endodontic procedures in necrotic mature teeth with periapical radiolucencies : a preliminary randomized clinical study. Journal of endodontics. 2019 Jul 1;45(7):863-72. https://www.gdcdental.com/products-detail.php?id=1079 Abbass MMS, El- Rashidy AA, Sadek KM, Moshy SE, Radwan IA, Rady D, Dörfer CE, Fawzy El-Sayed KM. Hydrogels and Dentin–Pulp Complex Regeneration: From the Benchtop to Clinical Translation. Polymers. 2020; 12(12):2935. https://doi.org/10.3390/polym12122935 65