The document discusses regenerative endodontics, which aims to regenerate dental pulp tissue using stem cells, growth factors, and scaffolds. It explains that mesenchymal stem cells from sources like dental pulp, bone marrow, or apical papilla can differentiate into odontoblast-like cells. Growth factors like VEGF, PDGF, and BMPs regulate stem cell differentiation and tissue regeneration. Scaffolds provide a structure for cell growth and differentiation. The regeneration process aims to restore the loose connective tissue and layer of odontoblasts that make up healthy dental pulp.
2. The new interesting progress in endodontic therapy is the
introduction of regenerative endodontics and dental pulp
revascularization .Regeneration of a functional pulp-dentin
complex relies on the foundation of tissue engineering and can be
viewed as a function of the spatially correct delivery of
appropriate stem cells and growth factors embedded within a
scaffold to restore, maintain, or improve tissue functions.
3. • Stem cells
• Morphogens or growth factors
• Extracellular matrix (scaffold)
• The delivery system
4. Stem cells are undifferentiated cells capable of self-
renewal/expansion (can divide many times) and able to
differentiate into specialized cell types.
So to know what type of stem cells we need we must know
what the dental pulp’s constituents?
5. The dental pulp
dental pulp is composed of a core of loose connective tissue
with fibroblasts as the major cell type , blood vessels, lymphatics
and neurons. The core tissue is embedded in an extracellular
matrix consisting of collagen and other fiber types and the core
with its constituents is surrounded by a layer of odontoblasts .
Pulpal mesenchymal stem cells are thought to be localized
in the perivascular region and the cell-rich zone of Hohl adjacent
to the odontoblastic layer; both have been proposed to serve as
cell sources for replacement odontoblasts .Thus , several cell
types must be developed in order to form this core of loose
connective tissue.
6. The regeneration of loose connective tissue has been
proposed to be similar to the process of the granulation
phase of wound healing, with the local release of
angiogenic growth factors such as vascular endothelial
growth factor (VEGF) and platelet-derived growth
factor (PDGF) playing key roles in coordinating
angiogenesis and the development of loose connective
tissue. Knowing that , the other focus is on generation
of the surrounding layer of odontoblasts.
7. Postnatal (adults)mesenchymal stem cells are
known to differentiate into odontoblast-like cells
and their resources are:
1. Dental pulp stem cells (DPSC).
2. Stem cells of human exfoliated deciduous teeth
(SHED).
3. Stem cells of the apical papilla (SCAP).
4. Dental follicle progenitor cells (DFPC).
5. Bone marrow-derived mesenchymal stem cells
(BMMSC).
8. Growth factors
Growth factors are extracellularly secreted signals
governing morphogenesis/organogenesis during epithelial-
mesenchymal interactions. They regulate the division or
specialization of stem cells to the desirable cell type, and
mediate key cellular events in tissue regeneration including cell
proliferation, chemotaxis, differentiation, and matrix synthesis .
9. Multiple types of growth factors are used in regenerative
endodontics including :
• Dexamethasone
• Dexamethasone and Vitamin D3
• Dexamethasone andAscorbate-2-phosphate and β-
Glycerophosphate,
• Insulin and Indomethacin and 3-Isobatyl-1-
methylxanthine (IMBX)
• Dexamethasone and Insulin and Ascorbate-2-phosphate
and Sodium pyruvate and TGF-β1
11. Scaffold:
A scaffold can be implanted alone or combined
with stem cells and growth factors to provide a three
dimensional physicochemical and biological
microenvironment or tissue construct for cell growth
and differentiation.
12. Ideal requirements of a scaffold:
1. Should be porous to allow placement of cells and growth
factors.
2. Should allow effective transport of nutrients, oxygen,
and waste.
3. Should be biodegradable, leaving no toxic byproducts.
4. Should be replaced by regenerative tissue while
retaining the shape and form of the final tissue
structure.
5. Should be biocompatible.
6. Should have adequate physical and mechanical
strength.
13. Types of scaffolds:
a) Biological/natural scaffolds :collagen ,glycosaminoglycans
,demineralized or native dentin matrix and fibrin.
b) Artificial scaffolds :(polylactic acid (PLA), polyglycolic
acid (PGA), polylactic-coglycolic acid (PLGA), polyepsilon
caprolactone ,hydroxyapatite/tricalcium phosphate,
bioceramics ,titanium , and hydrogels such as alginate or
variants of polyethylene glycol (PEG).
14. Terms and clinical methodologies related to endodontic
regeneration:
• Apexification is defined as a method to induce a calcified
barrier in a root with an open apex or the continued
apical development of an incompletely formed root in
teeth with necrotic pulp tissue. The outcome of an
apexification procedure is establishment of an apical
barrier against which an obturating material may be
placed.
15. • Apexogenesis, is 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,
thus no need to “revascularize” the canal space.
• Revascularization can be broadly defined as the
restoration of vascularity to a tissue or organ.
