Ecm

1. “The beauty of the natural world lies in the details”

2. DR. SUMAN MUKHERJEE
MDS (1ST YR)
DEPT. OF PERIODONTICS
Extracellular matrix

3. Contents : Session
1
• Introduction
• ECM Origin
• Forms of ECM
• Components of ECM
• Function of ECM
• Collagen
• Elastin
• Fibrillin
• Fibronectin
• laminins

4. • Integrins
• Proteoglycans & GAGs
• Conclusion
• Bibliography

5. Contents :
Session 2
• GAGs – types in periodontium (detail)
• MMPs
• TIMPs
• The influence of the extracellular matrix on
gene expression in the periodontium
• Future applications
• Abnormalities of ECM in diseased state.
• Conclusions
• Reference

6. Introduction • The intercellular substance of tissue was once
considered to be relatively homogeneous, nothing
more than a scaffold for cells to grow or a
medium to “glue” cells together.
• During the past half century, the perception of
this supposedly inert material has been revised
dramatically.
• Today, the intercellular substance of tissue, or the
extracellular matrix, is recognized as a complex,
interactive compilation of proteins in dynamic
equilibrium that can regulate the gene expression
of cells.
Autonomous extracellular matrix remodeling
controls a progressive adaptation in muscle stem cell
regenerative capacity during development

7. extracellular-matrix-protein
• Only recently has it been possible to
recognize how the presence of specific
molecules in the extracellular matrix interact
with genetically similar target cells to trigger a
biological response that culminates in a
distinct morphological and secretory result.

8. EXTRACELLULAR MATRIX ORIGIN
• The ECM appeared during evolution with the
advent of multicellular invertebrate animals.
• The contemporary animal species that represent
those early invertebrates contain the same
macromolecular components found in all ECM,
namely collagens, proteoglycans, and
glycoproteins.
• New matrix domains appeared in multicellular
animals that had not been present in primordial
single-cell organisms, and the new domains then
became conserved in the multicellular organisms.

9. • Moreover, ancestral protein
domains became genetically
rearranged in various matrix
proteins, yielding new
molecules, including some
whose functions remain to be
discovered.

10. Forms of Extracellular matrix
The extracellular matrix is composed of
two biochemically and morphologically
separate entities,
• Basement Membrane
• Interstitial Connective Tissue
Matrix

11. Interstitial matrix
• Present in the spaces between cells in the connective
tissue, and the parenchymal epithelium and underlying
vascular and smooth muscle structures.
• It is synthesized by mesenchymal cells (eg. fibroblasts)
• Forms a 3D amorphous gel structure
• Its major constituent are fibrillar and non-fibrillar
collagen, fibronectin, elastin, proteoglycan, hyaluronate
and others.

12. Basement membrane
• The interstitial matrix
becomes highly organized
around epithelial cells,
endothelial cells, and smooth
muscle cells, and forms
highly specialized
basement membrane
• Synthesized by contribution
of both underlying
mesenchyme and overlying
epithelium.

13. • It is porous structure forming a flat lamellar
“chicken wire” mesh.
• It’s major constituent are :
• Collagen type IV
• Laminin 12
• Entactin / Nidogen 2 isoforms
• Sulfated proteoglycans such as Perlecan and
Agrin

15. Components
of
Extracellular
Matrix
• Components of ECM can be categorized into 3
groups of proteins;
Fibrous structural proteins : Collagen, Elastin
and Fibrillin.
• Confers tensile strength and recoil.
Water Hydrated gels – Proteoglycans and
Hyaluronan
• Permits compressive resistance and lubrication.
Adhesive glycoprotein and receptors –
Fibronectin, Laminin & Integrins
• Connects ECM to one another & other cells.
Water – 65 %

16. Extracellular
macromolec
ule
• Only 5 classes of macromolecules
Collagen
Elastic Fibers
Proteoglycans
Hyaluronan
Adhesive Glycoproteins
• They can be mixed up in different proportions
for different functions.
Soluble – easily
hydrated
Insoluble – cannot
be hydrated

17. Functions of ECM • In addition to space filler other functions
are :
• Mechanical support - for cell anchorage ,
cell migration and maintenance of cell
polarity.
• Control of cell proliferation – by acting as a
depot of latent growth factors, binding and
displaying growth factors, and signaling
through cellular receptors.
• Scaffolding for tissue renewal – integrity of
ECM is critical for the organized
regeneration of tissues. So ECM disruption
results in defective tissue regeneration and
repair (e.g. Cirrhosis of Liver).
Cirrohosis: condition that liver is damaged to the point where
replacing damaged cells with healthy cells is impossible. At
this point, the liver loses its regenerative potential

18. • Establishment of tissue microenvironments :
BM acts as a boundary between epithelium and
connective tissue, and is also functional eg. In
kidney BM forms parts of filtration apparatus.
• Cellular Interactions : for maintaining normal
tissue architecture.

19. Collagen are the most abundant proteins in mammals.
(∼30% of total protein mass)
The collagen family comprises 28 members that
contain at least one triple-helical domain.
Synthesized by fibroblast & some epithelial cells
Contributes to stability of tissues & organs
It maintains their structural integrity
Main component of tendons, fascia, cartilage,
ligament, bone & skin.
Plays an important role in cell differentiation,
polarity & movement.
Fibroblast in a 3D collagen matrix

20. Human genome contains
42 distinct α genes.
Total 28 types of collagen
identified so far
Triple helix of 3 α chains
• It is an insoluble glycoprotein. (carbohydrate +
proteins)
• Collagen polypeptide primary structure

23. Synthesis of collagen
• Synthesis of a chain of pre pro-collagen on
ribosome
• Hydroxylation of lysine and proline in
rER/Golgi by lysyl -5- hydroxylase & prolyl-4-
hydroxylase
• Glycosylation : addition of galactose and glucose
to some hydroxylysine residues (galactosyl
transferase and glycosyl transferase)
• Assembly of α chains to form precollagen .
Reactions needs the formation of di-sulphide
bonds between registration peptides, at both
ends of pre pro-collagen.

24. • Formation of pro pre-collagen
molecules by exocytosis into the
extracellular space .
• Cleavage of registration peptides
is catalysed by pro collagen
peptidase. The resulting molecule
is tropocollagen .

25. • Oxidation- deamination of the
hydroxylysine, the removal of (NH2)
group has a net oxidation effect and the
formation on covalent crosslinks.
Reaction is catalyzed by lysine oxidase.
• Self assembly or polymerization of
tropocollagen molecules from collagen
fibrils.
• crosslinks between adjacent
tropocollagen molecules stabilizes the
fibrils.

26. The family of
collagen
proteins
• There are as many as 25 different genes that
code for at least 14 different collagen molecules.
• Six different collagen types have been detected
in the periodontium.

27. • The collagen molecule consists of 3 distinct
polypeptide chains, called IY. chains, that form
homotrimeric or heterotrimeric domains.
• Formation of the triple helix depends on the
amino acid composition of the protein and the
winding of the polypeptide chains.
• The amino acid sequence of the triple helix is
glycine-X-Y, where X and Y represent the imino
acids proline and hydroxyproline 30% of the
time.

28. • Due to steric hindrances, the smallest amino
acid, glycine, is crucial to the helix formation.
• This amino acid is in the position that
occupies the restricted space in which the 3
helical chains come together.
• The imino acids’ rigid, cyclic backbone
stabilizes the triple helix by limiting the
rotation.
• The triple helix domain serves two important
functions.

29. • It physically separates the globular domains
within the molecule and offers the potential for
lateral interactions from those amino acids in the
X-Y positions.
• The family of collagens can be separated into 7
broad groups :
• 1) fibrillar,
• 2) fibril-associated collagens with interrupted
triple helices,
• 3) sheet-forming,
• 4) beaded filaments,

30. • 5) anchoring fibrils,
• 6) growth plate-specific and
• 7) miscellaneous.

31. Fibrillar
collagens
• This class contains the most commonly
occurring collagen proteins and accounts for the
greatest percentage of mass in all connective
tissues.
• The characteristic of these collagens is to form
extensive linear aggregates. Fibril formation is an
exact, parallel configuration of collagen
molecules.
• The alignment of collagen molecules is a lateral
association of collagen molecules staggered by
67 nm.

32. • Included in the fibrillar
collagens are type I, type I
trimer, type II, type III,
type V and type XI
collagen.

33. Fibril-
associated
collagens
with
interrupted
triple helices
(FACITs)
• Unlike the quarter-staggered fibril collagens, this
class does not form fibrils.
• These collagen molecules consist of interrupted
triple helices and large amino-terminal domains.
• Fibril-associated collagens with interrupted
triple helices consist of 3 functional domains.
• One domain, consisting of 1-2 triple helices,
interacts and adheres to fibrils: a second domain,
also comprised of a triple helix, projects out of
the fibril; whereas the third domain, which
consists of a nonhelical, globular region, is
thought to be involved with matrix or cellular
interactions

34. • It has been suggested that fibril-associated
collagens with interrupted triple helices connect
fibrillar collagens to the matrix.
• Included in the fibril-associated collagens with
interrupted triple helices are type IX, type XII
and type XIV collagens.

35. Collagen
forming
sheets.
• These nonfibrillar collagens also have regions of
helical and nonhelical structural domains.
• Like the fibril-associated collagens with
interrupted triple helices, they are un- able to
associate into compact banded fibers.
• For example, type IV collagen forms a complex,
branching, net-like structure whose globular
domains interact with other type IV collagen
molecules

36. • Type VIII collagen is a dumbbell-shaped
molecule that forms regular hexagonal lattices.
• These collagens are found in basement
membranes, Descemet’s membrane and in the
cuticle and organic skeletons of worms.
• Included in the collagens forming sheets are
type IV and type VIII collagens.
Alport’s syndrome

37. Collagen
forming
beaded
filaments.
• Only type VI collagen is included in this protein
class.
• This collagen is a heterotrimeric molecule
consisting of a short triple helix domain with
very large nonhelical amino and carboxyl
regions.
• The collagen molecules form a tetramer, which
consists of two dimers positioned in a head-to-
tail orientation.

38. • The tetramers assemble into linear aggregates
that re- peat every 110 nm and are stabilized by
disulfide bonds.
• These beaded filaments often accrue in lateral
bundles to form fibers with a periodicity of 110
nm .
• Although the function of type VI collagen is not
known, pathological accumulations of type VI
collagen have been noted in several fibrotic
diseases and osteoarthritic disorders
Bethelem’s myopathy

39. Collagen
forming
anchoring
fibrils.
• Type VII collagen, the only collagen in this class,
is a homotrimeric molecule that contains a very
large globular region.
• At the carboxyl terminal of the molecule is a
large nonhelical domain composed of three 50-
nm arms that are capped by small globules;
• the amino terminal also has a globular region
but is not as large as the carboxyl terminal

40. • During assembly, the nonhelical region at the
amino terminal is cleaved and 2 molecules
overlap by 60 nm.
• These dimers associate in a linear, non-staggered
fashion to become a principal component of
anchoring fibrils.
• The cell type primarily responsible for secreting
type VII collagen is the keratinocyte.

41. • Type VII collagen forms an association between
the type IV collagen, in the basement
membrane, and the anchoring plaques, in the
connective tissue.
• This results in an interconnecting web of
interstitial collagen fibers, type VII collagen and
type IV basement membrane collagen, to secure
the basement membrane to the underlying
stroma

42. • Individuals with dystrophic epidermolysis
bullosa, a disease that exhibits a separation of
the epithelium from the connective tissue, have
exhibited qualitative or quantitative changes in
the type VII collagen.

43. Growth
plate-
specific
collagen
• Type X is a homotrimeric collagen that has
structural homology to type VIII collagen but,
unlike type VIII, has not been shown to produce
a sheet structure.
• Type X is secreted by hypertrophic
chondrocytes and has been associated with
endochondral bone formation.
• Although the function of type X is not known,
it has been suggested that it might influence the
remodeling of cartilage prior to calcification.

44. Miscellaneo
us collagen
• The collagen in this group, type XIII, has not
been well defined, and the proposed function
and chain stoichiometry are there- fore not
understood.
• Even though little information is available about
type XI11 collagen, it is known that the a chain
of this collagen is composed of 3 collagenous
and 4 non collagenous domains whose primary
transcript undergoes complex splicing.

45. Collagen
structure
function
relations
• Primary structure of collagen is tissue specific .
Type 1 in tendons and type 2 in cartilage.
• The secondary and tertiary structures are
specific substrate for the metalloprotein
enzymes collagenase that degrades collagen
fibers. Remodeling of tissues during wound
healing occurs by collagenase. Melting of
collagen to Gelatin (loss of tertiary structure)
spontaneously follows such degradation.
• The banding (quaternary structure) of collagen
fiber determines the blood clot forming
properties of collagen (primarily through
induction of platelet aggregation.)

46. • The architectural structure of collagen
determines the function of collagen fibers as
mechanical reinforcements of connective tissue
(tendons, skin, bone, arteries). Tendon fibers are
bundles of uniaxially aligned fibers that are
crimped. Skin (dermis) is a random planar array
of crimped collagen fibers. Bone is a ductile
ceramic (Hydroxyapatite) which is reinforced by
collagen fibers. Large blood vessels (aorta, large
arteries) are interpenetrating networks of
collagen and elastin fibers.

50. Clinical
correlation
• Genetic defects :
• Ehlers Danlos Syndrome – type
1,3,5 collagen mutation
• Osteogenesis Imperfecta – type 1
collagen mutation
• Others : Scurvy ascorbate
deficiency
Ehlers Danlos Syndrome

51. Osteogenesis imperfecta (OI) is a genetic
disorder that is commonly called “brittle
bone”
Vitamin C deficiency (Scurvy)

52. Elastin • Major protein component of tissues that
requires elasticity.
• Most prominent in skin. Also found in arteries,
lungs, cardiac valves, elastic ligaments &
cartilages.
• Composed of fibrillin fibrils and elastin
• Synthesized only by fetal and juvenile fibroblasts
Whatever is made until puberty has to last until
the end
Loss is responsible for wrinkles

53. • Polypeptide chains are cross linked to form
rubber-like, elastic fibers. Each elastin molecule
uncoils when the rubber is stretched & recoils
spontaneously as soon as the force is relaxed.
• 90 % of all amino acid residues of elastin are
non-polar (characterized by a high index of
hydrophobicity).
• Elastin fiber consists of a central core made of
elastin, surrounded by a peripheral network of
microfibrils.
• Overtime, tropoelastin accumulates within the
bed of microfibrils.

54. • More massively crosslinked than collagen and
have large hydrophobic segments that forms
globular compartments at rest.
• As stretch is exerted the hydrophobic domain
are pulled open, but the cross-linked keep the
tissue intact.
• Release of stretch tension allows the
hydrophobic domains of the protein to refold.
• Thus, elastin has more elasticity & less tensile
strength than collagen.

55. Elastic fibers
• Elastic fibers are composed of 2 distinct
parts, an amorphous component and a
microfibrillar component.
• Elastin, which makes up the insoluble,
amorphous component, is a highly
hydrophobic and non glycosylated protein.
• The elastin protein contains a high
percentage of glycine, proline and other
hydrophobic residues with little
hydroxyproline and no hydroxylysine .Fluorescence microscopy showing human cells
interacting with tropoelastin fibres. Green
marks the elastin, red is inside the human cells.

56. • The polypeptide chains of elastin,
tropoelastin, form multiple lysine-
derived covalent cross-links, using
desmosine and isodesmosine, to form
extensive networks.
• The microfibrillar component is located
around the periphery and scattered
throughout the amorphous component.
• Their function is to endow tissues with
the property of elastic recoil, and they
also regulate the bioavailability of
transforming growth factor β.Visualizing Tropoelastin in a Long-Term Human
Elastic Fibre Cell

57. Elastin
• It is composed principally of
glycosylated, hydrophilic amino acids,
which contain a higher amount of
cystine and cysteine, lower
concentrations of glycine and no
hydroxyproline, desmosine or
isodesmosine compared with elastin.
Healthy arteriole in eye, with tough, flexible elastin wall
(pink) red blood cells (red) and supporting collagen fibers
(web-like "netting," and yellow & green areas).

58. • Another constituent of elastic fibers is
oxytalan fibers. Oxytalan fibers are believed
to be immature or specifically modified
elastic fibers and consist of thin (0.5 to 2.5
pm in diameter) elastic-like fibers or
microfibrils that contain vicinal-glycol groups
as well as lectin-reactive carbohydrates
• Some investigators consider oxytalan fibers to
be artifacts of the staining process and the
origin, chemical composition, function and
significance of these fibers are therefore
disputed.Green, fibrillin-1-positive oxytalan fibers. Blue, nucleus.
The upper panel only contains green, while the lower
panel contains all three colors.

59. • Severe heritable elastic fibre diseases are
caused by mutations in elastic fibre
components; for example, mutations in
elastin cause supravalvular aortic stenosis
and autosomal dominant cutis laxa,
mutations in fibrillin-1 cause Marfan
syndrome and Weill-Marchesani syndrome,
and mutations in fibulins-4 and -5 cause
autosomal recessive cutis laxa.
• Acquired elastic fibre defects include
dermal elastosis, whereas inflammatory
damage to fibres contributes to pathologies
such as pulmonary emphysema and vascular
disease.
Marfan Syndrome

61. Fibrillin • Large glycoprotein secreted by Extracellular
fibroblast
• Found commonly in zonular fibers of lens,
periosteum, arterial wall.
• In the elastic fiber the peripheral microfibrillar
network that surrounds the core consists largely
of fibrillin.
• Types of fibrillin :
• Fibrillin 1 : major component of fibrillin
• Fibrillin 2 : have a role in early elastogenesis
• Fibrillin 3 : mainly located in brain
• Fibrillin 4 : structure similar to fibrillin 2
Immunofluorescence staining for fibrillin-1 (A) and fibrillin-2 (B)

62. Marfan’s Syndrome FBN1 mutation in chromosome
15
• It forms part of the insoluble
microfibril which acts as a
scaffold upon which elastin
fibers are deposited.
• Genetic disorder Marfan’s
Syndrome results from
mutation in fibrillin gene.

63. Fibronectin • The fibronectins are a heterogeneous group
of at least 200 different glycoproteins with
various biological properties.
• The general profile of fibronectin structure
consists of 2 identical, or nearly identical,
disulfide-linked polypeptides with a combined
molecular weight of approximately 450 kDa
• In each subunit reside distinct, tightly folded
globular regions that bind collagens, heparan
sulfate, proteoglycan ,fibrinogen, DNA as
well as prokaryote and eukaryote cells.
Human Intestinal Fibroblasts (HIF) -
Immunostaining for Fibronectin

64. • Fibronectins are secreted by fibroblasts,
keratinocytes and a variety of other cell
types and are found in the blood, the
extracellular matrix and at cell surfaces.
• Fibronectins exhibit a diverse number of
biological functions including cell
attachment and migration, wound healing,
phagocytosis and extracellular matrix
organization .
Human Fibronectin Antibody MAB19

65. Functions • Related to cell adhesion,
differentiation , growth & migration.
• Anchoring basal laminae to other
ECM.
• Plasma fibronectin forms a blood
clot, along with fibrin
• Related to cell movement – group of
embryonic cells follow a FN pathway
– FN guides macrophages into
wound area.

66. Laminin
• Laminins are cell adhesion molecules that comprise a
family of glycoproteins found predominantly in
basement membranes, which are the thin sheets of
extracellular matrix that underlie epithelial and
endothelial cells and surround muscle cells, Schwann
cells, and fat cells.
Laminin-111, as a representative model of laminin structure (LN laminin N-terminal
domain, LE laminin epidermal-growth-factor domain, L4 laminin 4 domain, LF
laminin four domain, LG laminin globular domain, Lβ laminin β-knob, i.e., a domain
that is present only in β chains and that interrupts the coiled coil of β chains, hinge
non-globular link between LG3 and LG4). The binding site for nidogens (γ1LEb3)
is shown in black

67. Basement membranes. Left Representations of
basement membrane (green) underlying epithelial
cells and surrounding muscle and Schwann cells.
Right Immunostaining with antibodies against the
laminin β2 chain on cross sections of skeletal
muscle and sciatic nerve
• Many laminins self-assemble to form
networks that remain in close association
with cells through interactions with cell
surface receptors
• Laminins are vital for many physiological
functions.
• The basal lamina serves as a structural
support for tissues and as permeability
barrier to regulate tissue movement of
both cells & molecules.
• It also modulates primordial germ cells
migration during embryogenesis.

68. • The biological effects of the laminins are to
a large extent presumably mediated by
surface receptors that link laminin matrices
to intracellular signaling pathways.
• The major laminin receptors are integrins
and nonintegrins. At least eight integrins
(α1β1, α2β2, α3β1, α6β1, α6β4, α7β1, α9β1,
αvβ3) can bind to laminins .
• Lutheran blood group glycoprotein
binds only to laminins containing the α5
chain (Suzuki et al. 2005; Scheele et al.
2007; Miner 2008).

69. Laminin-111 binding to
extracellular matrix molecules.
Binding sites for nidogens,
agrin, perlecan, fibulin-1, heparin,
and sulfatides are indicated.
Sulfatides bind to the α1LG4
domain, whereas several LG
domains are involved in binding
the α2, α4, and α5 chains.
Likewise, the major heparinbinding
site in the α1 chain is
α1LG4, whereas several relevant
heparin-binding sites are
found within the α2, α4, and α5
LG domains. The laminin network
is formed through polymerization,
in which the primary
interactions lead to a trimer
formation by the binding of
three different LN domains

71. Integrins : mediators of
cell adhesion
• Molecular glue of life.
• The term integrin was designated by Tamkun
et al. to indicate the integral role of this
glycoprotein in the organization of the
extracellular matrix and cytoskeleton.
• The integrins represent a collection of cell
surface proteins that mediate the binding of
cells to extracellular proteins and to one
another.Cell with an integrin sensor filmed using
multichannel fluorescence microscopy

72. • The integrins are heterodimers composed of an
a-subunit that is noncovalently linked to a
unique P-subunit.
• The a- and P-subunits are glycoproteins that
consist of an extensive amino-terminal in the
extracellular domain, a small hydrophobic
membrane domain and a small carboxyl terminal
domain in the cytoplasm .
• Alpha-subunits are more heterogeneous than the
P-subunits, and many a-subunits contain a 206-
amino-acid sequence known as the insert (I)
domain

73. • Although not all a-subunits contain this
region, integrins with the I-domain
interact with diverse macromolecules in
the extracellular matrix and may be
involved in the assembly and/or
organization of the extracellular matrix .
• The extra- cellular portion of the P-
subunit contains the arginine-glycine-
aspartate (RGD) binding region near the
amino terminus as well as up to 4
cysteine-rich regions that contribute to
rigidity and tertiary structure

74. Concepts of integrin function (a and b) Integrins are essential
for matrix deposition and therefore they organize the
microenvironment surrounding cells (a) and control cell-fate
decisions (b). (c) Key aspects of cell fate controlled by
integrins. (d) Disruption of the ECM–integrin–intracellular link
leads to several of the important diseases of humankind.
• The amino acid tripeptide, arginine-glycine-
aspartate, has been shown to be a common
recognition sequence on growth factors that bind
to integrins.
• The role of integrins evolves as the specificity and
affinity of different integrins continue to be
characterized and correlated with specific
biological responses.

75. • To date, integrins are considered
to be important for the
diapedesis of white cells,
interactions between T-cells and
macrophages during
inflammation, clot formation,
fibroblast and epithelial cell
migration during wound healing
as well as changes in cell-cell
adhesion during tumor invasion
and metastasis .

76. Proteoglyca
ns • The proteoglycans are a large and diverse
group of glycoproteins that are widely
distributed in mammalian tissues.
• A proteoglycan consists of one or more
sulfated polysaccharides covalently linked to
a protein core.
Proteoglycans (of gingival connective tissue )
• Decorion
• Versican

77. Glycosaminoglyc
ans
• The polysaccharide, called a glycosaminoglycan,
is a linear polymer consisting of repeating
disaccharides containing an N-acetyl hexosamine
and a hexuronic acid or hexose
• Glycosaminoglycans are highly anionic chains
that can vary in size from a few disaccharide
units to several thousand disaccharide units.
• The glycosaminoglycans are represented by
several species, including chondroitin-4-sulfate,
chondroitin-6-sulfate, heparan sulfate, heparin,
hyaluronic acid and keratin sulfate

78. • The variation of saccharide composition, length
and sulfation as well as protein core composition
affords an exceptional diversity of structure and
function for proteoglycans.
• The roles ascribed to proteoglycans in the
extracellular matrix have included everything
from physical maintenance of the matrix to cell-
cell interactions.

80. Glycosaminoglycans (of gingival connective
tissue )
 Chondroitin-4-sulfate
 Dermatan sulfate
 Heparan sulfate
 Hyaluronic acid

82. CONCLUSION
• Many gaps exist in our understanding of the
roles of extracellular matrix in cell biology and
its importance in life support.
• The function of cells in the periodontium is
the culmination of numerous, intricate
interactions between cells and the substances
that they secrete.
• As our understanding of the periodontium
evolves, we must not only catalogue
macromolecules but also begin to define the
nature of cell-matrix interactions in the
kaleidscope of extracellular matrix domains.Fluorescence micrograph of HeLa cells (human cervical
cancer cells) showing the extracellular matrix protein

83. BIBLIOGRAPHY • The extracellular matrix of the periodontium: dynamic
and interactive tissues Angelo Mariotti Periodontology
2000, Vol. 3, 1993, 39-63
• Origin of animal multicellularity: precursors, causes,
consequences—the choanoflagellate/sponge transition,
neurogenesis and the Cambrian explosion Thomas
Cavalier-Smith Philosophical Transactions Of The
Royal Society B Volume 372, issue 1713
• Laminins Madeleine Durbeej Cell Tissue Res (2010)
339:259–268 DOI 10.1007/s00441-009-0838-2
• Current concepts of extracellular matrix Marvin L.
Tanzer J Orthop Sci (2006) 11:326–331

84. • New advances in probing cell–extracellular matrix
interaction Allen P. Liu, Ovijit Chaudhuri Sapun H.
Parekh Integr. Biol., 2017, 9, 383
• Laminins Madeleine Durbeej Cell Tissue Res (2010)
339:259–268
• The extracellular matrix at a glance Christian Frantz,
Kathleen M. Stewart and Valerie M. Weaver Journal
of Cell Science 123, 4195-4200
• Extracellular Matrix: A Matter of Life and Death Stefano
Marastoni, G. Ligresti, and E. Lorenzon Connective
Tissue Research, 49:203–206, 2008

85. Acknowledgement

86. Previous Seminar
Questions

87. Turnover
time for
epithelial
wounds
• 10 – 14 days
(Wound repair: role of immune–epithelial interactions G
Leoni,1 P-A Neumann,2 R Sumagin,3 TL Denning,4 and A
Nusrat5 Mucosal Immunol. 2015 Sep; 8(5): 959–968)

88. Ulcers and
abrasion
• abrasion is the act of abrading, wearing, or
rubbing off; the wearing away by friction while
• ulcer is (pathology) an open sore of the skin,
eyes or mucous membrane, often caused by an
initial abrasion and generally maintained by an
inflammation and/or a
• The definition of an ulcer is more specific: a
localized disruption of the surface of an organ
or tissue, the result of death of inflamed tissue.
Another similar term is erosion, meaning a
shallow ulcer. n infection.

89. Gingival
ablation
• Ablation is removal of material from the surface
of an object by vaporization, chipping, or other
erosive processes.
• In medicine, ablation is the same as removal of a
part of biological tissue, usually by surgery.
• In periodontics, mainly used as a procedure for
gingival depigmentation.

90. Creeping
attachment
• "CREEPING ATTACHMENT" is a
phenomena that was described by
Goldman as the "post operative
migration of the gingival marginal tissue
in a coronal direction over portions of a
previously denuded root".
• The recommended operative treatment
varied and included mucogingival
procedures, free gingival grafts, and
coronal repositioned flaps.

91. • Clinically the migration occurred slowly during a
long period of time and apparently resulted in an
attachment to the tooth that could not be disturbed
with the use of the periodontal probe.
• "Creeping attachment" must be differentiated from
bridging or surgical attachment where the graft
attaches directly to the exposed root surface as a
direct result of the surgical procedure.
• There are many clinical reports in the literature on
the affect of free grafts on the gingival margin level.
• The reports varied but most showed "creeping
attachment" of 0.12 to 3.5 mm during a period of 2
years.

92. Pilot study
• A pilot study, pilot project or pilot
experiment is a small scale
preliminary study conducted in order
to evaluate feasibility, time, cost,
adverse events, and improve upon the
study design prior to performance of
a full-scale research project.

93. Disinfection
of
toothbrush
• Soak your toothbrush in antibacterial mouthwash. Rinse
thoroughly before using again.
• For everyday cleaning, you can store your toothbrush in a
small cup of hydrogen peroxide. When you brush your
teeth, change out the hydrogen peroxide.
• Boil your toothbrush for about 3 minutes. Although it is
hard on your toothbrush, boiling water will most germs.
• A toothbrush can be put into the silverware compartment of
the dishwasher to be sanitized. Run your toothbrush
through on the hot cycle without soap.
• Purchase a UV toothbrush sanitizer. These nifty gadgets
work by combining steam with dry heat to sanitize your
toothbrush. However if you don’t want to shell out the
money, studies show that soaking your toothbrush in
Listerine works almost just as well.

94. All of the methods tested, including antimicrobial chemical agents and dishwasher
use,were effective to reduce the bacterial counts of S. mutans,S. aureus, E. coli,
and L. rhamnosusin toothbrushes. However, the most effective method for all
tested bacteria was 50% white vinegar, which is cost-effective, easy to access,
and appropriate for household use. Further studies determining all of the effects of
white vinegar, including its biocompatibility or toxicity, may increase clinicians'
awareness about its antimicrobial capacity.
Evaluation of toothbrush disinfection via different methods BASMAN ADIL et al. Braz. oral
res. vol.30 no.1 São Paulo 2016 Epub Dec 15, 2015

95. How to
assess
healing:
clinically
• The Wound Healing Society often uses the mnemonic
device TIME, which is a comprehensive description of
the key elements associated with impaired wound healing,
as follows:
• T = Tissue: Note the presence of devitalized or necrotic
tissue, as well as specific characteristics of the tissue
surrounding the wound
• I = Inflammation or infection: Note areas both within and
surrounding the wound site
• M = Moisture: Note the state of moisture balance and
whether the wound is macerated
• E = Edge of the wound: This includes assessing for re
epithelialization versus non advancing or non healing
edges; assessing the blood supply to the edges of the
wound

96. Healing
assessment
tools
 Pressure Sore Status Tool.
Sessing Scale
 Wound Healing Scale
 Sussman Wound Healing Tool.
Wound depth.
Progression over time
Photographs
Wound volume
Wound perimeter and surface area

97. Why no
scars in oral
regions
• Various reasons have been suggested for minimal scarring
in the oral cavity,
• including distinct fibroblast phenotype,
• the presence of bacteria that stimulate wound healing and
• the moist environment and growth factors present in saliva.
• Animal lovers know that their pets like to lick their wounds,
and animal studies have shown that licking and saliva
application enhance skin wound healing and reduce
inflammation.
• This effect of saliva is attributed mainly to its relatively high
concentration of epidermal growth factor (EGF), and
topical use of artificial saliva has been suggested as a
treatment for skin burn wounds.
Human palatal wounds heal quickly with
minimal clinical scarring. a) Healing of
human palatal wounds (10 × 2 mm), 3 days
(posterior) and 7 days (anterior) after
wounding. b) Healing of the same wounds
after 60 days.

98. Which
structure
was taking
the stains
(Mira-2-Ton)

99. DR. SUMAN MUKHERJEE
MDS (1ST YR)
DEPT. OF PERIODONTICS
V.S.D.C.H.
Extracellular matrix