REGENERATIVE ENDODONTICS

 TISSUE ENGINEERING - an interdisciplinary field that applies the principle of engineering and life sciences
towards the development of biological substitutes that restore, maintain, or improve tissue function
 TISSUE REGENERATION - replacement of injured tissue by the same resident cells, or by differentiation
of progenitor/stem cells into tissue committed cells

REPAIR VS REGENERATION
REPAIR:
• Damaged tissue is vital
• Process when healing takes place by proliferation of connective tissue elements resulting in fibrosis
and scarring
• Cementum-like, bonelike or periodontal-like tissues instead of a normal dental pulp
REGENERATION:
• Damaged tissue is completely necrotic
• The process when healing takes place by proliferation of parenchymal cells and usually results in
complete restoration of the original tissues
• Closely resembles normal pulp tissue

APICAL SCAR

REGENERATIVE ENDODONTICS
• Can be defined as biologically based procedures “designed to replace damaged structures”, including
dentin and root structures, as well as cells of the pulp-dentin complex.
• GOALS:
• Primary – elimination of symptoms and the evidence of bone healing
• Secondary – increased root length and root wall thickness
• Tertiary – positive response to vitality tests
• Pinnacle of regenerative goals
• Histologic confirmation for structural and functional restoration
COMPONENTS OF REGENERATIVE ENDODONTICS
• Key elements of tissue regeneration are
• Stem Cells
• Growth factors
• Scaffold
(NOTES NI DOC:
A reliable cell source capable of differentiating into odontoblasts stem cell
Growth factors that can stimulate cellular proliferation and directing cellular differentiation
An appropriate scaffold to promote cell growth and differentiation)

STEM CELLS
• Undifferentiated cells that can differentiate into various specialized cell types
(NOTES NI DOC:
Stem cells are long-tern SELF-RENEWING and thus can generate any tissue for a lifetime unlike other progenitor
cells
Stem cells are UNDIFFERENTIATED CELLS
Stem cells are less specified than progenitor cells. Progenitor cells can only differentiate into their “target” cell
type)

EPITHELIAL STEM CELLS MESENCHYMAL STEM CELLS

Ameloblasts Odontoblasts
Pulp
Cementoblasts

(NOTES NI DOC:
The principles of tissue engineering to the development of regenerative endodontics requires correct
understanding of stem cell that contribute to the formation of dental hard and soft tissues.

Epithelial – mesenchymal interactions: tooth formation

DENTAL EPITHELIAL CELLS (Ameloblasts and ameloblasts precursor are eliminated after tooth eruption)….
EPITHELIAL CELLS that could be stimulated in vivo to form enamel re not present in human adult teeth

MESENCHYMAL CELLS are primarily required for the formation of dental pulp and are studied widely as
compared to the epithelial stem cells)
(NOTES NI DOC:
SHED – formation of mineralized tissue, which can be used to enhance oro-facial bone regeneration
(osseointegration of implants, calvarial defects) – PRIMARY INCISORS and CANINES
DPSC – regenerate a dentin-pulp-like complex composed of a mineralized matrix of tubules lined with
odontoblsts and fibrous connective tissue containing blood vessels
SCAP – located at the apex of developing human permanent teeth – essential for root development – loosely
attached to the developing root and can easily be detached with a pair of tweezers
SCAP SHOWS HIGHER PROLIFERATION THAN DPSC
PDLSC – showed capacity to regenerate typical cementum and pdl like structure contribute to periodontal
tissue repair
DFSC - differentiate into cementum forming like cells, osteoblasts of the alveolar bone, pdl fibroblasts
BMSC –
GROWTH FACTORS
• Regulate stem cells to form the desirable cell type
• They promote differentiation of mesenchymal stem cells into odontoblast-like cells
• Platelet derived growth factors
• Bone Morphogenetic Proteins
• Transforming Growth Factor B
• Vascular Endothelial Growth Factors
• Insulin like growth factors
• Nerve growth factors
• Stromal cell derived growth factor
(NOTES NI DOC:
GROWH FACTORS PLUS STEM CELLS ACCOMPLISH ISSUE ENGINEERING
IN VIVO THERAPY – WHERE BMP ARE DIRECTLY APPLIED TO EXPOSED OR AMPUTATED PULP
EX VIVO THERAPY – WHERE ISOLATION OF DPSCS with bmp – TRANSPLANTATION TO REGENRATE DENTIN)

SCAFFOLDS
• Provides a physiochemical and biological 3D microenvironment for cell adhesion, growth
differentiation and migration
• It has a lot of purpose and function.
(NOTES NI DOC:
Functions:
Allow cell attachment and migration
Deliver and retain cells and biomechanical factors
Enable diffusion of vital cell nutrients and expressed products
Provides structural support and shape to construct)

REQUIREMENTS OF A SCAFFOLD
• Should be porous to allow placement of cells and growth factors
• Should allow effective transport of nutrients, oxygen, and waste
• Should be biodegradable, leaving no toxic by-products
• Should be replaced by regenerative tissue while retaining the shape and form of the final tissue
structure
• Should be biocompatible
• Should have adequate physical and mechanical strength
BIOLOGICAL BASIS FOR REGENERATIVE ENDODONTIC THERAPY
• Historically, long-term calcium hydroxide treatment was used to induce apexification of immature tooth
with pulpal necrosis before placing an obturation material such as gutta-percha in the root canal system.
• While the success rate of calcium hydroxide apexification is reported to be as high as 95%, there are
several associated problems.