Pulpal angiogenesis and

pulpal response to caries-

regenerative options
Dr. Hariprasad L
2nd MDS
Department of conservative dentistry and
endodontics
CONTENTS
▪ INTRODUCTION
▪ ANGIOGENESIS
▪ PULPAL ANGIOGENESIS
▪ SIGNIFICANCE OF
ANGIOGENESIS
▪ PULPAL RESPONSE TO 2
CONTENTS
▪ CURRENT MANAGEMENT
▪ REGENERATIVE OPTIONS
▪ ODONTOBLAST DIFFERENTIATING
MATERIALS
▪ SUMMARY
▪ CONCLUSION 3
INTRODUCTION

4
5
What is angiogenesis?
Angiogenesis is the formation of new blood vessel
from preexisting capillaries .

Is responsible for the majority of the blood vessels

formed during physiological and pathologic
conditions. 6
Why angiogenesis in regeneration?
The physiological architecture of a healthy dental pulp
-Vascular
-Neuronal components
A regulated interplay between tissue vasculature and
nerves is critical to maintaining homeostasis.

7
 In regenerative procedures

▪ Blood vessels enable influx of oxygen and nutrients to

support the newly formed pulp-like tissue.

▪ The success of tissue engineering relies on rapid

establishment of microvascular networking to provide
blood and nutrients for cells 8
▪ Blood vessels allow for the influx of immune cells
that provide a mechanism of defense as well as
further regulation of the angiogenic response in
tissues.

9
Mechanism of angiogenesis during tissue injury

10
NEUROPEPTIDES
▪ Calcitonin gene related peptide
▪ Substance P
▪ Neurokinin A
▪ Neuropeptide Y
▪ Vasoactive intestinal peptide
11
12
Proangiogenic growth factors

▪ VEGF
▪ FGF
▪ PDGF

13
14
ANGIOPOIETINS

▪ Group of proteins with remarkable role in

angiogenesis and lymphangiogenesis.

▪ 2 major forms including Ang-1 and Ang-2

15
16
Anti angiogenic factors

▪ Endostatin
▪ IGFBP3
▪ uPA
▪ TIMP-1
▪ PAI-1.
17
Angiogenesis in regeneration
▪ Studies have shown that DPSC can produce
angiogenic and anti angiogenic factors.
▪ The dentin matrix also produces factors like VEGF,
IGF, PDGF etc.
▪ Growth factors produced externally.
ANGIOGENESIS
18
PULPAL RESPONSE TO
CARIES
Regenerative apporaches
19
 CAS Costa et al, Chapter 1: Pulp Biology, Endodontic Science, Pg 1-22.

Basic characterization of dental pulp space.

20
Mild response to inflammation

21
Moderate response to inflammation

22
Severe response to inflammation

23
Current strategies
▪ Indirect pulp capping
▪ Direct pulp capping
▪ Pulpotomy
▪ Apexogenesis
▪ Apexification
24
Regenerative approach

Factors embedded in dentin:

 Heparin-binding growth factor
 Transforming growth factor (TGF)-β1, TGF-
β3
 Insulin-like growth factors I and II
 Platelet-derived growth factor
25
 Bone morphogenetic protein-2 (BMP-2)
 Angiogenic growth factors

26
▪ During the carious dissolution of dentin, it
is believed that the soluble pool of TGF-β1
can diffuse across intact dentin.

27
This concept of growth factors released from
dentin acting on the DPSC is the basis of
regeneration in the field of
dental caries management.

28
Materials promoting odontoblastic differentiation

▪ BIOCERAMICS:
Biodentin
MTA
Bioaggregate
▪ LASERS 29
▪ STATINS
▪ BIGUANIDES
▪ VITAMIN D

30
MAPK pathway
▪ ERK
▪ P38
▪ JNK MAPKs 

31
32
Biodentin

▪  Bioactive calcium silicate-based cement.

▪ ‘Dentin substitute’
Tricalcium silicate , Calcium carbonate , Zirconium
Oxide: powder
Calcium chloride, water and polymer : liquid

Dhillon JS, Batra M, Saini M. MTA versus Biodentine: Review of Literature with a Comparative 33
Analysis. J Clin Diagn Res. 2017;11(8)
34
▪ Biodentin induced SCAP proliferation.

35
Expression of genes such as
 RUNX2
 OSX
 DSPP
 ALP

36
MTA
▪ MTA is basically a mechanical mixture of three powder.
▪ Portland cement (75%), bismuth oxide (20%) and gypsum (5%).

Dhillon JS, Batra M, Saini M. MTA versus Biodentine: Review of Literature with a Comparative
Analysis. J Clin Diagn Res. 2017;11(8)

37
38
39
BIOAGGREGATE
▪ Nano particle sized tricalcium silicate, tantalum
oxide, calcium phosphate, silicon dioxide.
▪ Induces mineralization associated gene expression in
mouse osteoblast cell lines 

40
41
LASERS
▪ Low-power laser irradiation (LPLI) promotes
proliferation by cellular stimulating signal pathways.
▪ Osteoblast proliferation via the activation of
MAPK/ERK.
▪ Low-power diode-LI also boosts proliferation in human
dental pulp-derived fibroblast-like cells.
42
43
STATINS

▪ Simvastatin used for odontogenic and osteoblastic

differentiation.
▪ Based on the dosage it can accelerate or retard the
differentiation.

44
At low concentrations
▪ dentin sialophosphoprotein (DSPP)
▪ dentin matrix acidic phosphoprotein 1 (DMP-1)
▪ alkaline phosphatase (ALP)
▪ collagen type 1 alpha 1 (Col1A1)

45
▪ osteocalcin, osteopontin
▪ runt-related transcription factor 2
▪ bone morphogenetic protein 2 (BMP-2)

46
BIGUANIDES

▪ Metformin
▪ Genes expressed- DSPP, DMP-1,
Runx2, and OCN.

47
VITAMIN D
▪ Vitamin D deficiency causes hypocalcified dentin and delayed
tooth eruption.
▪ Vitamin D crucial for dentin mineralisation

ODONTOBLAST
48
Upregulated expression:
Dentin Sialophosphoprotein (Dspp)
Dentin Matrix Protein1 (Dmp1)
Alkaline phosphatase (ALP)

49
midazolam

50
Upregulated expression:
ALP
DSP

51
CONCLUSION

▪ ANGIOGENESIS: is influenced by series

factors like Proangiogenic factors, Angiopoetic
and anti angiogenic factors.
▪ Angiogenesis crucial for regenerative
endodontics.
52
▪ Paves a new path to the field of regeneration.
▪ Current stratergy of dental caries management:
SURGICAL APPROACH

53
 FUTURE

REGENERATIVE
APPROACH
54
References
▪ Kaur M, Singh H, Dhillon JS, Batra M, Saini M. MTA versus Biodentine:
Review of Literature with a Comparative Analysis. J Clin Diagn Res. 2017
Aug;11(8):ZG01-ZG05. 
▪ Saberi E, Farhad-Mollashahi N, Sargolzaei Aval F, Saberi M. Proliferation,
odontogenic/osteogenic differentiation, and cytokine production by human
stem cells of the apical papilla induced by biomaterials: a comparative
study. Clin Cosmet Investig Dent. 2019;11:181-193
▪ Borzabadi-Farahani, A. (2016). Effect of low-level laser irradiation on
proliferation of human dental mesenchymal stem cells; a systemic review.
Journal of Photochemistry and Photobiology B: Biology, 162, 577–582.
55
doi:10.1016/j.jphotobiol.2016.07.022 
▪ N Wongwatanasant , J Jantarat, H Sritanaudomchai Effect of Bioceramic
Materials on Proliferation and Odontoblast Differentiation of Human Stem
Cells from the Apical Papilla:J Endod 2018;1–6
▪ Y Jung, S‐M Woo Effect of Biodentine and Bioaggregate on odontoblastic
differentiation via mitogen‐activated protein kinase pathway in human
dental pulp cells:Int end;48; 177-184
▪ Raghavendra SS, Jadhav GR, Gathani KM, Kotadia P. Bioceramics in
endodontics - a review. J Istanb Univ Fac Dent. 2017;51(3 Suppl 1):S128-
S137. Published 2017 Dec 2. doi:10.17096/jiufd.63659
56
▪ D Soares et al Biological Analysis of Simvastatin-releasing Chitosan Scaffold
as a Cell-free System for Pulp-dentin Regeneration J Endod 2018;44:971–
976
▪ Woo SM, Lim HS, Jeong KY, Kim SM, Kim WJ, Jung JY. Vitamin D
Promotes Odontogenic Differentiation of Human Dental Pulp Cells via ERK
Activation. Mol Cells. 2015;38(7):604-609.
doi:10.14348/molcells.2015.2318
▪ T Karakida Potential for Drug Repositioning of Midazolam for Dentin
Regeneration Int. J. Mol. Sci. 2019, 20(3), 670
57