Regenerative Endodontics

Ajo Babu GeorgeIV BDS

CONTENTS

• Introduction

• Components of Regenerative Endodontics

INTRODUCTION• Regenertive endodontics are biologically based procedures

designed to replace damaged structures ,including dentin and root structures, as well as cells of pulp-dentin complex.

• Concept :Normal, sterile granulation tissue developed in the root canal for revascularization will stimulate the cementoblasts/ undifferentiated mesenchymal cells (periapex) and lead to calcific material formation at periapex or lateral dentinal walls.

• Goals : Primary goal- elimination of symptoms and the evidence of

bone healing. Secondary goal-increased root length or wall thickness. Tertiary goal-positive response to vitality tests.

COMPONENTS OF REGENATIVE ENDODONTICS

• The three key elements of tissue regeneration are:Stem cellsGrowth factors Scaffold

Stem cells

• According to Diogenes et al., regenerative procedures are all stem cell based therapies.

• Stem cells are undifferentiated cells that are capable of differentiating into various specialized cell types. They can be pluripotent or multipotent in nature. They are located in stem cell niches.

• Types of stem cells: Dental pulp stem cells (DPSC) stem cells of the apical papilla (SCAP) Stem cells from human exfoliated deciduous teeth (SHED) Dental follicle stem cells (DFSC) Bone marrow stem cells (BMSC) Periodontal ligament stem cells (PDLSCs) Inflamed periapical progenitor cells (iPAPCs) Tooth germ progenitor cells (TGPCs) Salivary gland stem cells (SGSCs)

Dental pulp stem cells

• stem cells derived from the dental pulp • can form pulp like tissue , in future it is possible to

replace infected pulp tissue of a paining tooth with newly generated pulp like tissue instead of doing RCT ,thus preserving the vitality of the tooth

• It also has the ability to form bone that is useful for the osseointegration of dental implants, thus increasing its success rate .

Stem cells of the apical papilla

• A unique population of dental stem cells known as stem cells from the root apical papilla (SCAP) is located at the tips of growing tooth roots . The apical papilla tissue is only present during root development before the tooth erupts into the oral cavity .

• SCAP have the capacity to differentiate into odontoblasts and adipocytes .

• These cells are CD24+ but expression is down regulated upon odontogenic differentiation in vitro coincident with alkaline phosphatase up regulation.

Stem cells from human exfoliated deciduous teeth (SHED)

• Dental pulp of human exfolliated deciduous teeth contains multipotent stem cells from human exfoliated deciduous teeth (SHED). were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. Thus, exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering.

• have higher rate of proliferation.• have potential to form bone which is useful during

osseointegration of dental implants• have the potential to repair calvarial defects in

immuno-compromised mice .

Dental follicle stem cells (DFSC)

• The dental follicle is a loose ectomesenchyme-derived connective tissue sac surrounding the enamel organ and the dental papilla of the developing tooth germ before eruption .

• It is believed to contain progenitors for cementoblasts,PDL and osteoblasts.

• Dental follicle cells (DFC)form the PDL by differentiating into PDL fibroblasts that secrete collagen and interact with fibers on the surfaces of adjacent bone and cementum.

• Dental follicles contain progenitor cells which have the capability of differentiating into cementum forming cells (cementoblasts), osteoblasts of the alveolar bone, and periodontal ligament fibroblasts.

Bone marrow stem cells (BMSC)

• Bone marrow-derived cells (BMDCs) have the potential to engraft into several tissues after injury, but whether they can become dental tissue-specific progenitor cells under normal conditions and the relationship of these cells to the tissue-resident cells are unknown

• Bone marrow progenitor cells communicate with dental tissues and become tissue-specific mesenchymal progenitor cells to maintain tissue homeostasis.

Periodontal ligament stem cells (PDLSCs)

• have potentials of regenerating typical cementum and periodontal ligament like structure .

• tissue of the periodontium made by stem cell can be used as a treatment modality to replace the

• diseased periodontium around teeth so as treatment to mobility of teeth

• According to Hargreaves,stem cells like SCAP,DPSCs,iPAPCs,PDLSCs,BMSCs are most commonly used in regenerative endodontics.

• These cells have te capacity of differentiating into odontoblast-like cells facilitating a progressive repopulation of the radicular pulp space , promoting organized tissue repair ,angiogenesis and reinnervation.

Growth factors

• Biological factors regulate stem cells to form the desirable cell type.

• They promote the differentiation of mesenchymal stem cells into odontoblast-like cells.

Platelet derived growth factorsBone morphogenetic proteins (BMPs)Transforming growth factor bVascular endothelial growth factorFibroblast growth factors Insulin like growth factorNerve growth factorStromal cell derived growth factor I

BONE MORPHOGENETIC PROTEINS (BMPs)• Comprises a subgroup of the superfamily TGF(Transforming

growth factor b) and are involved in cell proliferation, differentiation and apoptosis.

• Have strong osteoinductive and chondrogenic effects.• BMP2,BMP4,BMP7 &BMP11 invoved in mineralization.

Scaffold

• A scaffold provides a physiochemical and biological 3-D micro environment for cell adhesion ,growth differentiation and migration. It contains the growth factors.

• Functions : Supports cell organization and vascularization. Aids cell proliferation and differentiation. Contains nutrients,antibiotics for improved and faster

tissue development.• Classification :-

Natural – collagen,platelet rich plasma ,fibrin, glycosaminoglycans

Synthetic – polylactic acid ,polyglycolic acid ,polylactic-co-glycolic acid

REVASCULARIZATION• Revascularization, as defined by Andreasen, is a the

restoration of the vascularity to a tissue or organ.

• Mechanism of revascularization ,according to Shah N : Vital pulp cells at the apical end of root canal

proliferate into newly formed matrix and odontoblasts, under the influence of HERS. Atubular dentin is laid in the apical end and lateral aspects of dentinal walls leading to apexogenesis and a thus strengthening and reinforcement of root occurs.

Multipotent dental pulp stem cells (immature permanent teeth)from the apical end might be seeded on to the existing dentinal walls and differentiate into odontoblasts and deposit tertiary or atubular dentin.

Stem cells in the periodontal ligament can proliferate

and grow into the apical end and within the root canal

and hence deposit hard tissue at apex and lateral walls.-

cementum and Sharpey’s fibers in newly formed

tissues.

Extensive proliferating property of SCAP & bone

marrow- instrumentation beyond confines of root –

bleeding –mesenchymal stem cell transplantation from

bone.

Regeneration of Dentin -Pulp complex• Three strategies to regenerate dentin-pulp complex have been

proposed:a. Regeneration of entire tooth.b. Local regeneration of dentin-pulp complex from

amputed dental pulp.c. Regeneration of dental pulp from apical dental pulp or

peri- apical tissues.• Growth factors like bone morphogenetic proteins (BMPs) and

fibroblast growth factors(FGFs), stem cells and scaffolds are essential for tissue engineering to regenerate tissues.

• Stem cells differentiate into specific cells for tissue defects , growth factors like BMPs ,induce proliferation of stem cells.

• Scaffolds with extracellular matrix properties support for cell proliferation ,differentiation and tissue formation.

a) Regeneration of entire tooth

• Accepted as a model of organ replacement and regeneration therapy.

• Tooth germ can be bioengineered using 3D organ germ culture method in which dental epithelial and mesenchymal cells from isolated tooth germs cultured in scaffolds ( synthetic polymers –polylactic-co-glycolic acid ; bio ceramics- hydroxyapatite , tricalcium phosphate, calcium carbonate hydroxyappatite)

b) Local regeneration of dentin-pulp complex from amputed dental pulp

• Induction of appropriate pulp wound healing and formation of new dentin in dentin defects are essential in regeneration of dentin-pulp complex.

• It was reported that BMP-2 with dentin powder induced dentinogenesis in dentin cavity with pulp exposure.Here stem or progenitor cells where induced from residual pulp through the exposure site in the floor of the cavity.

• Ultrasound mediated delivery of growth differentiating factor -11 (GDF-11) in dental pulp stem cells through sonoporation induced reparative dentinogenesis

c) Regeneration of dental pulp from apical dental pulp or peri- apical tissues

• Begins with identication of stem cells in the apical areas of developing teeth in which root formation is incomplete.

• mesenchymal stem cells in apical papilla (SCAPs) differentiate into odontoblast-like-cells that participate in pulp wound healing and regeneration.

• Bone marrow derived mesenchymal stem cells (BMMSC) has multipotent abilities and undergoes osteogenic differentiation.

• Periapical tissues include bone marrow and PDL which is the source BMMSCs. Localization of SCAPs & BMMSCs in the apical region --- induction for dentin-pulp complex regeneration

CLINICAL PROTOCOL REGENERATIVE ENDODONTICS

INDICATIONS• Teeth with necrotic pulp and an immature apex.• Pulp space not needed for post/core ,final restoration• Patient compliance.• No allergy to the medicaments to be used.ROLE OF ANTIBIOTIC PASTE• Antibiotic pastes are a combination of more than one antibiotic

mixed into a consistency of a paste.• The triple antibiotic paste-commonly used-

ciprofloxacin,metronidazole, minocycline(1:1:1) in a macrogol/propyleneglycol vehicle.

• Remains below CEJ and concentration is maintained to 0.1mg/ml and chamber is sealed with dentin bonding agents.

Local anesthesia, Isolation, access cavity preparation

Irrigation with 20ml of 1.5%NaOCl/5 min and saline rinse (20ml/ canal ,5min)

Drying with paper points

Placement of intracanal medicaments

Ca(OH)2

Low conc.triple antibiotic paste

Temp sealing with cavit/IRM/GIC

Recall patient after 1-4 weeks.

FIRST APPOINTMENT REGENERATIVE ENDODONTICS THERAPY

Assess response to initial treatment.

Signs of symptoms of infections persists

No signs /symptoms

Addtnl Rx time with antimicrobial pastes

Alternative antimicrobials to be considered

Local anesthesia (3%mepivacine without vasoconstrictor)

Irrigation with 20ml of 17% EDTA,drying with paper points

Intracanal bleeding- k file 2mm past apical foramen

Blood in cavity till CEJ, 3-4 mm restorative material

Resorbable matrix over clot

White MTA(mineral trioxide aggregate)/ Ca(OH)2,capping –3-4mm GIC

SECOND APPOINTMENT –REGENERATIVE ENDODONTIC THERAPY

FOLLOW --UP

• Clinical and radiographic examination• No pain ,swelling or sinum tract formation.• Resolution of periradicular radiolucency(6-12months of Rx)• Increase in width of canal walls (12—24months of Rx)• Increased root length• Pulp vitality tests.

ADVANTAGES AND DISADVANTAGES

ADVANTAGES• Achieve continued root development (root lengthening )and

strengthening due to enforcement of lateral dentin walls with hard tissue deposition.

• Obturation of canal is not required.• Splitting of root during lateral condensation avoided.• After control of infection, completed in a single visit.DISADVANTAGES • Discoloration due to minocyclinein antibiotic paste.• Prolonged treatment peroid compared with MTA apical barrier

technique.

POTENTIAL CAUSES OF FAILURE

• Poor root development.• Insufficient bleeding during procedure.• Pulp calcifications/obliterations.

CONCLUSION

• Regenerative endodontics holds promise of restoring pulp-dentin complex in teeth with immature roots and necrotic pulps.

• Procedure has advantages than traditional treatment of increasing root wall thickness as well as root length while maintaining immune competency.

• Significant scientific hurdles need to be overcome with continued growth in knowledge and armamentarium.

REFERENCES

• Grossman’s endodontic practices-13th edition –Suresh Chandra,V.Gopikrishna

• Regenerative Endodontics:regeneration or repair-Stéphane R.J. Simon, DDS, PhD, Phillip L. Tomson PhD-Journal of Endodontics.

• Regenerative Endodontics-Biological basis of Regeneration of Dentin-Pulp Complex- Ariane Berdal, PhD -Journal of Endodontics