“Periodontal Regeneration- New Vistas”- Guest lecture as a part of Dr NTRUHS Zonal CDE programme at SVS Institute of Dental Sciences, Mahabubnagar, India on 12/3/2013 and at Meghna Dental College, Nizamabad, India on 31/7/2013.

1. Dr R Viswa Chandra MDS;DNB
Reader
Department of Periodontics
SVS Institute of Dental Sciences
Mahabubnagar AP

2. INTRODUCTION
Periodontitis results in the
• Apical migration of junctional
epithelium over connective
tissue.
• Contamination of root surface
by bacteria and endotoxin
• Destruction of Progenitor
cells*
• Lack of chemotactic stimuli*
*Chen FM, Sun HH, Lu H, Yu Q. Stem cell-delivery
therapeutics for periodontal tissue regeneration.
Biomaterials. 2012 Sep;33(27):6320-44.

3. Multiple, specialized
cell types and
attachment
complexes
Avascular tooth
surfaces
Diverse microbial
flora
Stromal-Epithelial
Interactions
Slow and Varied Healing patterns
INTRODUCTION

4. PERIODONTAL REPAIR
• Repair > Regeneration*
• Common in conventional therapy
• Long JE because of rapid epithelial
turnover is the commonly seen
entity
• Reattachment of existing fibers
• Long JE is not inferior to a
dentogingival epithelium of
normal length+
*Ellegaard B et al. New attachment after treatment of interradicular
lesions. J Periodontol. 1973 Apr;44(4):209-17.
+Magnusson I et al. A long junctional epithelium--a locus minoris
resistentiae in plaque infection? J Clin Periodontol. 1983
May;10(3):333-40.

5. Whether a damaged tissue heals by regeneration or is
repaired depends upon two crucial factors*
(1) the availability of needed cell type(s), and
(2) the presence or absence of signals necessary to
recruit and stimulate these cells
These factors are not mutually exclusive
*Grzesik WJ, Narayanan AS. Cementum and periodontal wound healing and regeneration. Crit Rev Oral Biol
Med. 2002;13(6):474-84
WHY REPAIR?

6. Regeneration is distinct from tissue repair and is
characterized by replacement of the damaged tissues
with something that may be inferior to the original
tissue both structurally and functionally
To achieve successful periodontal regeneration, the
formation of a functional epithelial seal, the insertion
of new connective tissue fibers into the root, the
reformation of a new acellular cementum (New
Attachment) reformed on the root surface and the
restoration of alveolar bone height are required
PERIODONTAL REGENERATION

7. TRUE VS FALSE
PERIODONTAL REGENERATION
“Thus, if the ambition is to
regenerate the periodontal
ligament and the alveolar bone
that have been lost due to
periodontitis, it should aim at
reestablishing a new cementum
and neighboring cells”
Lars Hammarström. The 1998 Jens Waerhaug Lecture in
Periodontology. Scandinavian Society of Periodontology.

8. Some therapies have also
provided a promising
potential for significantly
improving clinical
parameters and
demonstrating substantial
“fill” of treated defects.
However, only limited
histologic evidence of true
regeneration has been
demonstrated with the
majority of these therapies.
TRUE VS FALSE
PERIODONTAL REGENERATION

9. “Despite conclusive evidence that some regeneration
may occur following regenerative procedures,
complete regeneration may be an unrealistic goal for
many situations due in part to the complexity of the
biological events, factors, and cells underlying
successful periodontal regeneration”*
It is emphasized that the three tissues of the
periodontium are dental tissues and that growth and
maintenance of the alveolar bone are regulated by
cells at the root surface+
*AAP. Position Paper Periodontal Regeneration. J Periodontol 2005;76:1601-1622.
+Grzesik WJ, Narayanan AS. Cementum and periodontal wound healing and regeneration. Crit Rev Oral Biol
Med. 2002;13(6):474-84.

10. PERIODONTAL REGENERATION
An Ambiguous term?

11. • Bioengineering: The use of artificial tissues, organs, or
organ components to replace damaged or absent parts of
the body. Stress is placed on the use of grafts/scaffolds
• Regenerative Medicine is the promise of regenerating
damaged tissues and organs in the body by replacing
damaged tissue and/or by stimulating the body's own
repair mechanisms to heal previously irreparable tissues
or organs.
• The term regenerative medicine is often used
synonymously with tissue engineering, although those
involved in regenerative medicine place more emphasis
on the use of stem cells to produce tissues.

13. No Regeneration without Cementum?
Grzesik WJ, Narayanan AS. Cementum and periodontal wound healing and regeneration. Crit Rev Oral
Biol Med. 2002;13(6):474-84.

14. ACHIEVING PERIODONTAL REGENERATION
Chen FM, Jin Y. Periodontal tissue engineering and regeneration: current approaches and expanding
opportunities. Tissue Eng Part B Rev. 2010 Apr;16(2):219-55.

15. Benatti BB et al. Physiological features of periodontal regeneration and approaches for periodontal tissue engineering
utilizing periodontal ligament cells. J Biosci Bioeng. 2007 Jan;103(1):1-6.
BENATTI (2007)* CLASSIFICATION
OF REGENERATIVE MATERIALS

16. Harvested bone grafts and graft substitutes
Growth factor-based bone graft substitutes
Cell-based bone graft substitutes
Ceramic-based bone graft substitutes
Polymer-based bone graft substitutes
Miscellaneous
LAURENCIN (2006)* CLASSIFICATION
OF REGENERATIVE MATERIALS
*Laurencin C, Khan Y, El-Amin SF. Bone graft substitutes.
Expert Rev Med Devices 2006; 3 : 49-57.

18. SCAFFOLDS
A three-dimensional scaffold
may play an important role
in periodontal regeneration.
The intended use of bone
scaffolds is for implantation
in critical size bone defects
Successful scaffold design
should stimulate new bone
growth resulting, at the end
state, in native bone tissue
with no trace of the scaffold.

19. SCAFFOLDS
Natural Extracellular Matrices
Calcium Phosphate Scaffolds
Synthetic Polymer Scaffolds
Viral Vectors
Retroviral vector
Stem Cells
MSC
Non-Viral Vectors
PDGF, TGF
Dangaria SJ et al. Extracellular matrix-mediated differentiation of periodontal progenitor cells. Differentiation.
2009 Sep-Oct;78(2-3):79-90.

20. Taba M et al. Current concepts in periodontal bioengineering. Orthod Craniofac Res. 2005 Nov;8(4):292-302.

21. EFFECTS OF SCAFFOLDS
ON PERIODONTAL REGENERATION
WHOLE BONE LEVEL
Restoration of the
function and
structural support
by
Osteogenesis
Osteoinduction
Osteoconduction
Cell exclusion
ARCHITECTURAL LEVEL
Restoration of the
trabecular structure
of the bone
by
Osteogenesis
Osteoinduction
Cell exclusion
TISSUE LEVEL
Restoration of the
lamella and the
microarchitecture
By
Osteoinduction
Cell exclusion

22. Notably, even with autogenous grafts, the formation of
functional periodontal fibers and new cementum is
limited
With allografts, some reports have described a minor
degree of true regeneration
The value of alloplastic materials for periodontal or
bone regeneration remains questionable
Cell exclusion and space-making approaches to the
treatment of periodontal defects seem to lead to
more favourable healing
Zohar R, Tenenbaum HC. How predictable are periodontal regenerative procedures? J Can Dent Assoc.
2005 Oct;71(9):675-80.

23. WHAT’S NEW?

24. WHAT’S NEW?
Hypoxia inducible factors (HIFs), a key stimulator of blood
vessel formation along with GTR procedures
Novel cellular allograft containing native mesenchymal
stem cells and osteoprogenitor cells
Grafting material that incorporates autogenous teeth
(AutoBT)
Scaffolding Matrices for Delivery of Cells and Genes for
Periodontal Engineering

25. CELL BASED MATERIALS
provide cells
that are able to
differentiate to
multiple cell
types to
promote
regeneration
to use cells
as carriers to
deliver growth
or cellular
signals

27. Exhibit stem cell
functionality
Secrete
growth factors
Immuno
modulation
Rios HF et al. Cell- and gene-based therapeutic strategies for periodontal regenerative
medicine. J Periodontol. 2011 Sep;82(9):1223-37.
contains several heterogeneous
cell populations, ranging from
osteogenic lineages
putative stem cell marker
STRO-1 and the perivascular cell
marker CD146
Expresses IGF, PDGF-BB and
TGF-β
Immune inhibiting and
stabilizing effect

28. While the ability of adult progenitor and stem cells to
commit to various periodontal lineages is well-
established, it is not clear to what extent these
regenerates represent a “true periodontium” on
biological and functional levels.
A major obstacle that remains today is how to
maximize the use of cells delivered to a passive or
permissive environment where there is context for
the type of cell needed as just 2.9% of the cells are
known to survive in the periodontal tissues

29. WHAT’S NEW?

30. WHAT’S NEW?
Hepatocytes from dental pulp cells.
Stem cells for implant primary stability

31. BIOLOGIC FACTORS
ANGIOGENIC
Factors
FGF, PDGF
SIGNALING
Factors
EMD, BMP

35. Benatti BB et al. Physiological features of periodontal regeneration and approaches for periodontal tissue
engineering utilizing periodontal ligament cells. J Biosci Bioeng. 2007 Jan;103(1):1-6.

36. Bashutski JD, Wang HL. Biologic Agents to Promote Periodontal Regeneration and Bone
Augmentation. Clin Adv Periodontics 2011;1:80-87.

37. A recent review on EMD suggests that there is strong evidence
for enamel matrix proteins to support wound healing and new
periodontal tissue formation
PDGF-BB is a growth factor involved in wound healing that
stimulates the regenerative potential of periodontal tissues,
including bone, cementum, and periodontal ligament
Some preliminary evidence suggested that BMP-2 could induce
periodontal regeneration, but some adverse healing events
such as ankylosis and root resorption
Platelet-rich fibrin (PRF) contains high amounts of bioactive
growth factors to enhance wound healing through increased
chemotaxis, proliferation, differentiation, and angiogenesis

38. CONCLUSION
The future of the regeneration may depend on
the merging of various technologies and
biological concepts, including the possible use
of biological barriers, various bone and
periodontal growth inducers, and artificial
matrices that will attract or carry the cells
necessary for regeneration.

39. *Elangovan S, Avila-Ortiz G, Johnson GK, Karimbux N, Allareddy V. Quality assessment of systematic reviews on
periodontal regeneration in humans. J Periodontol. 2013 Feb;84(2):176-85.
*
Too many ingredients spoil the broth?