apical regeneration ppt

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  1. 1. SEMINAR ON APICAL REGENERATION Presented by: Astha Jaikaria Deptt. of Pediatric and Preventive Dentistry 6/1/2017 1
  3. 3. Introduction Irreversible damage to immature permanent teeth as a result of noxious infection or local trauma before normal physiological closure of the apical structure represents a real clinical challenge. One of the major risks facing immature teeth with interrupted root development is weakened fracture resistance of the dentin walls. Important requirement for regeneration of pulp tissues is to obtain stem cells capable of differentiating into odontoblasts. 6/1/2017 3
  4. 4. Regenerate a functional pulp-dentin complex within a patients existing permanent tooth. Helps restore natural functions:-formation of replacement dentin and maintenance of tissue immunity and neural sensation. 6/1/2017 4
  5. 5. Nakahara has summarized potential methods for regenerating an entire tooth. First approach -incorporating principles of tissue engineering, involves seeding appropriate stem cells onto scaffolding materials, such as has been used for periodontal regeneration, controlled by the addition of specific growth factors and/or signaling molecules. Second approach - replicating the natural developmental processes of embryonic tooth formation - Artificial tooth germs are transplanted into the bodies of animal hosts where there is enough blood flow to support tissue formation. 6/1/2017 5
  6. 6. DEFINITIONS: Regenerative endodontics has been defined as biologically based procedures designed to replace damaged structures such as dentin, root structures, and cells of the pulp-dentin complex.(Cohen) Revascularization describes reestablishment of vascular supply to immature permanent teeth. (Andreasen JO and Andreasen FM) Revitalization describes ingrowth of vital tissue that does not resemble the original lost tissue. Regeneration is a biologic process whereby the continuity of the disrupted or lost tissue is regained by new tissue which restores structures and function. 6/1/2017 6
  7. 7. Endodontic regeneration is the replacement of damaged structures, including dentin and root structures, as well as cells of the pulp- dentin complex. It also indicates that the pulp is completely necrotic (complete degradation) and a tissue (pulp like) must be formed that may function as the original tissue. Maturogenesis has been defined as physiologic root development, not restricted to the apical segment.Weisleder et al (2003) 6/1/2017 7
  8. 8. Apexogenesis, is defined as a vital pulp therapy procedure performed to encourage continued physiologic development and formation of the root end. An important distinction is that apexogenesis is indicated for teeth in which there has been no loss of vascularity, -- no need to revascularize the canal space. 6/1/2017 8
  9. 9. HISTORY: Rule and Winter(1966) documented root development and apical barrier formation in cases of pulpal necrosis in children. Nygaard- Ostby & Hjortdal(1971) performed studies that can be considered the forerunner of pulpal regeneration. Myers and Fountain in 1974 attempted to regenerate dental pulp with blood clot filled in the canal. Skoglund et al (1978) demonstrated that in a traumatic avulsion, blood vessels slowly grow from apex toward the pulp horn by replacing the necrosed pulp left behind after the avulsion injury.6/1/2017 9
  10. 10. Kling M et al (1986) - incidence of revascularization was enhanced by 18%, if the apex showed radiographic opening of more than 1.1 mm. Age is an important issue since some clinical studies suggest that younger patients have a greater healing capacity or stem cell regenerative potential. Dental pulp tissue engineering was first tested by Mooneys group (1996) 6/1/2017 10
  11. 11. Bohl KS (1998) described a tissue engineering approach to dental pulp tissue replacement utilizing cultured cells seeded upon synthetic extracellular matrices. Huang et al (2006): isolated human pulp stem cells may differentiate into odontoblasts on dentin in vitro. 6/1/2017 11
  12. 12. FACTORS GOVERNING REGENERATIVE ENDODONTIC PROCEDURES: (1) Stem cells that can differentiate and support the continued root development. (2) Growth factors for induction of cellular proliferation and differentiation. (3) Appropriate scaffold to promote cellular growth and differentiation. 6/1/2017 12
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  14. 14. Regenerative endodontics includes: Root canal revascularization via blood clotting. Stem-cell therapies such as : Post-natal stem-cell therapy Pulp implantation Scaffold implantation Injectable scaffold delivery Three-dimensional cell printing Gene delivery 6/1/2017 14
  15. 15. Pulp tissue-engineering triad Triad diagram 6/1/2017 15
  16. 16. Stem Cells Pulpal mesenchymal stem cells: localized in the perivascular region and the cell-rich zone of Hohl adjacent to the odontoblastic layer may serve as cell sources for replacement odontoblasts. Local release of angiogenic growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Platelet-rich plasma has about a three- to sixfold increase in VEGF and PDGF. 6/1/2017 16
  17. 17. Types of stem cells Stem cell type Cell Plasticity Source of stem cell Totipotent Each cell can develop into a new individual Cells from early (13 days) embryos Pluripotent Cells can form any (over 200) cell types Some cells of blastocyst (514 days) Multipotent Cells differentiated, but can form a number of other tissues Fetal tissue, cord blood, and postnatal stem cells including dental pulp stem cells 6/1/2017 17
  18. 18. Five different types of postnatal mesenchymal stem cells have been reported to differentiate into odontoblast-like cells: Dental pulp stem cells (DPSC) Stem cells of human exfoliated deciduous teeth (SHED) Stem cells of the apical papilla (SCAP) Dental follicle progenitor cells(DFPC) Bone marrow-derived mesenchymal stem cells(BMMSC) Cells that express mineralized nodules and DSP as odontoblast-like.6/1/2017 18
  19. 19. Growth Factors/Morphogens Trigger the differentiation of selected mesenchymal stem cell populations into odontoblast-like cells. Application of dexamethasone greatly increased the differentiation of human dental pulp cells into odontoblast-like cells. Unlikely that a single growth factor will result in maximal differentiation. TGF-1 is the only TGF subtype detectable in human dentin. 6/1/2017 19
  20. 20. EDTA strongly exposed immunoreactive TGF-1 from human dentin, with appreciably smaller activities released after treatment with Ca(OH)2, NaOCl, MTA, or citric acid. Other growth factors:- Bone morphogenetic protein (BMPs) platelet-derived growth factor (PDGF) transforming growth factors (TGFs) fibroblast growth factors (FGFs)and growth/differentiation factor 11 (Gdf11). 6/1/2017 20
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  22. 22. Factor Primary Source Activity Usefulness Bone morphogenetic proteins Bone matrix BMP induces differentiation of osteoblasts and mineralization of bone BMP is used to make stem cells synthesize and secrete mineral matrix Colony stimulating factor A wide range of cells CSFs are cytokines that stimulate the proliferation of specific pluripotent bone stem cells CSF can be used to increase stem cell numbers Epidermal growth factor Submaxillary glands EGF promotes proliferation of mesenchymal, glial and epithelial cells EGF can be used to increase stem cell numbers 6/1/2017 22
  23. 23. Factor Primary Source Activity Usefulness Fibroblast growth factor A wide range of cells FGF promotes proliferation of many cells FGF can be used to increase stem cell numbers Insulin-like growth factor-I or II I - liver IIvariety of cells IGF promotes proliferation of many cell types IGF can be used to increase stem cell numbers Interleukins IL-1 to IL-13 Leukocytes IL are cytokines which stimulate the humoral and cellular immune responses Promotes inflammatory cell activity 6/1/2017 23
  24. 24. Factor Primary Source Activity Usefulness Nerve growth factor A protein secreted by a neurons target tissue NGF is critical for the survival and maintenance of sympathetic and sensory neurons. Promotes neuron outgrowth and neural cell survival Transforming growth factor-beta Dentin matrix, activated TH1 cells (T-helper) and natural killer (NK) cells TGF- is anti- inflammatory, promotes wound healing, inhibits macrophage and lymphocyte proliferation TGF-1 is present in dentin matrix and has been used to promote mineralization of pulp tissue 6/1/2017 24
  25. 25. Factor Primary Source Activity Usefulness Platelet-derived growth factor Platelets, endothelial cells, placenta PDGF promotes proliferation of connective tissue, glial and smooth muscle cells PDGF can be used to increase stem cell numbers Transforming growth factoralpha Macrophages, brain cells, and keratinocytes TGF- may be important for normal wound healing Induces epithelial and tissue structure development 6/1/2017 25
  26. 26. Scaffolds Appropriate scaffolding is necessary to: (1) provide a spatially correct position of cell location (2)regulate differentiation, proliferation, or metabolism. Extracellular matrix molecules control the differentiation of stem cells Appropriate scaffold might selectively bind and localize cells,contain growth factors and undergo biodegradation over time. 6/1/2017 26
  27. 27. Scaffolds can be classified as - natural or synthetic. Examples of natural scaffolds : collagen glycosaminoglycans demineralized or native


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