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CONTENTS
• INTRODUCTION
• HISTORY
• STRUCTURE
• HISTOLOGY
• TYPES
• BIOSYNTHESIS
• DEGRADATION
• COLLAGEN IN GINGIVA
• COLLAGEN IN PERIODONTAL LIGAMENT
• COLLAGEN IN CEMENTUM
• COLLAGEN IN ALVEOLAR BONE
• AGE CHANGES
• ABNORMALITIES OF COLLAGEN
• THERAPEUTIC APPLICATIONS
• CONCLUSION
• REFERENCES
INTRODUCTION

The name ‘collagen’ comes from Greek Kolla

meaning ‘glue prod uc er’ and in Frenc h, the word
collagene designates glue producing constituents
because collagenous tissues were used as sources of
glue and gelatin.
C o l l age n i s the mo st abund ant pro te i n i n
mammals and accounts for 25-30% of their protein
content. It is the main f ibrous component of skin, bone,
 Fibers made up of collagen have a high

tensile strength. Therefore this protein is an

important structural component in tissues
such as the periodontal ligament and muscle
tendons in which the mechanical forces
need to be transmitted without loss.
Apart from their structural role collagens
can also influence cell shape, differentiation
and many other cellular activities.
 HISTORY

• The molecular and packing structures of collagen have

eluded scientists over decades of research. The f irst
evidence that it possesses a regular structure at the
molecular level was presented in the mid-1930s.
• In 2006, it was conf irmed that the microf ibrillar structure
of adult tendon as described by Fraser, Miller, Wess
(amongst others) was closest to the observed structure.
 STRUCTURE

• Triple helical structure.

• Composed of 3 polypeptide alpha chains coiled around
each other to form the triple helix configuration.

• The individual polypeptide chains of collagen contain app.

1000 amino acid residues
• Each a chain contains sequence of three

repeating amino acids.

• There are around 3 amino acids per turn.
• Glycine occupies every third position in the

repeating amino acid sequence Gly – X – Y where

X and Y are amino acids other than glycine
• Proline frequently occupies

the X and Y positions

• Hydroxyproline and

hydroxylysine are
two unique amino acids.
Vertebrate collagens
exhibit the two of them in
the Y positions.
• The a chains are left handed helices that wrap around
each other into a right handed rope like triple helical rod.
• Each such helix is around 1.4 nanometers in diameter
and 300 nanometers in length.
1
1 1.5 nm
2
300 nm
(Gly-Xaa-Yaa) 338
• Triple helical structure is stabilized by an extensive
ne t wo rk o f hyd ro ge n bo nd s, c o v al e nt c ro ssl i nks,
electrostatic and hydrophobic interactions, and vander
waals forces.
• The triple helical molecules of collagen assemble and
form elongated f ib rils, and then rod like f ib ers in the
tissues.

• The f ib ril formation occurs by a quarter staggered

alignment i.e.each helix is displaced longitudinally from its

neighbour by about one-quarter of is length.

 CHEMICAL COMPOSITION

• The most abundant constituent is glycine

 HISTOLOGY
• Fresh collagen f ibers are colorless strands, about 1 –
100µm thick that usually follow a wavy course without
branching in tissues. Hence called as “White Fibres”
• Staining of Collagen

 Haematoxylin and Eosin stain

 Van Gieson stain- collagen- red
 Masson trichrome stain- collagen- blue
 Russell modif ic ation of the Movat pentachrome stain-
Collagen fibers- yellow
 PicroSirius Red (polarized)
FUNCTIONS

• Scaffolding for the body

• Controls cell shape and differentiation
• Regeneration of broken bones
• Proliferation of blood vessels
• Healing of wound
 TYPES

• The collagen superfamily contains at least 27 types of

collagens that together constitute the most abundant
proteins found in the body. All collagens are composed of
three polypeptide alpha chains coiled.
• The collagen superfamily is subdivided into the nine
subfamilies largely based on their supramolecular
assemblies.
Type Notes Gene(s) Major function

This is the most abundant collagen of

the human body. It is present in scar
tissue, the end product when tissue Prov ides tensile
COL1A1,
I heals by repair. It is found in tendons, strength to connective
COL1A2
skin, artery walls, the endomysium of tissue
my of ib ri l s, f ib roca rti l a ge, a n d th e
organic part of bones and teeth.
Hyaline cartilage, makes up 50% of all Prov ides tensile
II cartilage protein. Vitreous humour of the COL2A1 strength to connective
eye. tissue
T his is the collagen of granulation
tissue, and is produced quickly by young
Prov ides tensile
f ib roblasts before the tougher type I
III COL3A1 strength to connective
collagen is synthesized. Reticular f iber.
tissue
Al s o f o u n d i n a r t er y w a l l s , s k i n ,
intestines and the uterus
C O L 4 A 1 ,
Structural network of
basal lamina; eye lens. Also serves as C O L 4 A 2 ,
basal laminae
part of the filtration system in capillaries C O L 4 A 3 ,
IV together with laminins,
and the glomeruli of nephron in the C O L 4 A 4 ,
p roteog l y ca n s a n d
kidney. C O L 4 A 5 ,
entactin/nidogen
 most interstitial tissue, assoc. with C O L 5 A 1 , C O L 5 A 2 , Provides tensile
V
type I, associated with placenta COL5A3 strength
most interstitial tissue, assoc. with C O L 6 A 1 , C O L 6 A 2 , Binding with cells and
VI
type I COL6A3 matrix
Strengthens epithelial
forms anchoring f ib rils in dermal
VII COL7A1 – connective tissue
epidermal junctions
junction
Tissue support,porous
VIII some endothelial cells COL8A1, COL8A2
meshwork,
Atta ches f unctiona l
FACIT collagen, cartilage, assoc. with C O L 9 A 1 , C O L 9 A 2 ,
IX groups to surface of
type II and XI fibrils COL9A3
type II fibrils
h y p er t ro p h i c a n d m i n era l i z i n g
X COL10A1 Calcium binding
cartilage
Provides tensile
strength, controlling
XI cartilage COL11A1, COL11A2
lateral growth of type II
fibrils
FACIT collagen, interacts with type I
M o d u l a t e s f ib r i l
XII co n t a i n i n g f ib ri l s , d eco ri n a n d COL12A1
interactions
glycosaminoglycans
transmembrane collagen, interacts
with integrin a1b1, f ib ronectin and Cell matrix, cell
XIV FACIT collagen COL14A1 Modulates fibril interactions
Endothelial, perineural, muscle, Associates with heterotypic
XVI some epithelial basal laminae, COL16A1 II/IX/XI f ibrils and f ibrillin- 1
cartilage and placenta filaments
tra nsmembra ne colla gen, a lso
XVII COL17A1 Cell attachment to matrix
known as BP180, a 180 kDa protein
XVIII source of endostatin COL18A1 Eye development
XIX FACIT collagen COL19A1 Muscle differentiation
Corneal epithelium, skin, cartilage,
XX COL20A1 Associates with fibrils
tendon, heart
XXI FACIT collagen COL21A1 Maintain extrcellular integrity
XXII Tissue junctions COL22A1 -cell adhesion ligand
MACIT collagen – heart, retina,
XXIII COL23A1 -cell-matrix interaction
metastatic tumor cells
Regulation of typeI
XXIV Bone, cornea COL24A1
fibrillogenesis
XXV Neurons COL25A1 Neuron adhesion
Developing and adult ovary and
XXVI EMID2 Unknown
testis
XXVII Cartilage, ear, eye, lungs COL27A1 Cell attachment to matrix
1. Fibrillar collagens (Types I, II, III, V, XI, XXIV, and XXVII):
• highly organised manner in the extracellular compartment
to form fibrils with a typical 64-nm banding pattern.
• Triple helical contains an uninterrupted stretch of 338 to
343 aa
• Type I collagen is the most abundant in most connective
collagen tissues.
2. Basal lamina collagen (Type IV):Called anchoring filaments
• Similar in size to type I but does not assemble as fibrils
• Frequent nonhelical sequences and aggregates in a
sheetlike, chicken-wire configuration.
• Type IV collagen is a major component of the basal lamina
and is a product of epithelial cells.
3. Fibril-associated collagens with interrupted triple helices
(FACIT):
• Collagens IX, XII, XIV, XVI, XIX, XX,XXI, XXVI, and XXII
• Consists of proteins in which collagenous domains are
interrupted by noncollagenous sequences.
• chains that have different lengths and are found in various
locations in different tissues.
• Several of the FACIT collagens associate with f ib rillar
collagens and other extracellular matrix components.
•
4. Network-forming collagens: Type VIII, X
• assembles into a hexagonal lattice, which is believed to
impart compressive strength while providing an open,
porous meshwork.
• Type X collagen has a similar size and structure and is
largely restricted to the hypertrophic zone of the epiphyseal
cartilage growth plate.
5. Anchoring fibril collagen: Collagen VII
• unusually large nonhelical ends making up two thirds of
the size of the molecule.
• The C-terminal ends associate to form dimers that
subsequently are assembled into the anchoring f ibrils that
e xte nd fro m the basal lamina into the und e rlying
connective tissue.
6. Microfibril forming collagen: Type VI collagen
• has large N- and C-terminal globular
domains that associate in an end-to-end
fashion, forms beaded filaments.
• Type VI collagen is present in most

connective tissues.
• This collagen has binding properties for

cells, proteoglycans, and type I collagen

and may serve as a bridge between the cells
and the matrix.
7. Transmembrane collagen types XIII, XVII, XXIII, and XXV:
• The se c o l l a ge ns a re t ra nsm e m bra ne pro t e i ns w i t h
extrac ellular c ollagenous d omains and a C-terminal
noncollagenous domain that functions in cell adhesion.
• Type XVII collagen is found in hemidesmosomes of basal
epidermal cells.
• Type XIII collagen is present in focal

adhesion sites of fibroblasts and at

cell-matrix interfaces in some epithelia,
muscle, and nerves.
8.Multiplexin (endostatin-forming) collagens:
• Type XVIII collagen is a component of basal laminae of
epithelial and endothelial cells and is believed to
stabilize structures of the basal lamina.
• It has multiple interruptions in the central helical domain
and a large, unique C-terminal nonhelical domain.
9. Proteins containing helical collagenous domains:
• There is also a highly heterogenous group of proteins that
contain collagen domains but have not been def ined as
collagen
These include :
• the subcomponent C1q of complement,
• the tail structure of acetylcholinesterase,
• the pulmonary surfactant proteins SP-A and SP-D,
• mannan-binding protein, etc…
SYNTHESIS

major producers of Limited amount of

collagen collagen is produced

Fibroblasts
Chondroblasts Epithelial

Osteoblasts cells
Odontoblasts Endothelial
Cementoblasts cells
Muscle
cells
The entire process of collagen biosynthesis can be best
understood under the following stages

• Intracellular steps in collagen synthesis

• Extracellular collagen biosynthetic events
• Regulation of synthesis
STEP 1 :Gene expression
• Selection and Transcription of the procollagen genes
• Processing initial mRNA transcript.
• Eac h d ifferent mRNA is then translated on the
polysomes
• Messenger RNA directs the assembly of specif ic amino
acids into polypeptide chains on ribosomes associated
w i t h t h e ro u gh e n d o pl a sm i c re t i c u l u m t o fo r m
preprocollagen, which contains a leader or signal
sequence that directs the polypeptide chain into the
lumen of the endoplasmic reticulum.
• These initial polypeptide chains are about one and a half
times longer than those in the f inal collagen molecule
because they have N- and C-terminal extensions that are
important for assembly of the triple-helical molecule. As
it enters the endoplasmic reticulum, this leader sequence
is enzyrnatically removed
Translational and post translational events
STE P 2: Hyd roxylation of proline resid ues to obtain
hydroxyproline (in RER)
– catalyzed by the enzyme prolyl-4-hydroxylase
– Free 02, ferrous iron, a-ketoglutarate, and ascorbic acid
are required for this reaction.
– the hydroxylation secures the chains in the triple helix
of collagen

OH OH

OH
A CHAIN
STEP 3: Hydroxylation of lysine residues to obtain
hydroxylysine
• the enzyme lysyl hydroxylase is essential
• formation of the intermolecular cross-links that stabilize
collagen molecules within fibrils.

OH OH OH

OH OH
STEP 4: Glycosylation of some hydroxlysine residues (IN
RER)
– gluc ose and galac tose are ad d ed by enzymes
glycosyl transferase
OH
and galactosyl transferase
OH OH

OH OH
Gal

Glu

As the synthesis of pro α chains is completed they

join together at C terminal end
STEP 5: Assembly of the 3 alpha chains forms procollagen
– formation of disulphide bonds ( enzyme disulphide
isomerase ) between parts of the polypeptide chains
known as registration peptides at the C-terminal
– three chains associate, align and the triple helix forms in
a zipper-fashion giving procollagen

s s s
s s s
s s s
s s s

C-Terminal

N-Terminal
Step:5 cont
Formation of these disulf id e bonds assists in
the registration of the three collagen molecules
to form the triple helix, winding from the
carboxy terminal end.

s s s
s s s
s s s
s s s

C-Terminal
N-Terminal
STEP 6: Secretion of procollagen molecules by exocytosis
into the extra cellular space. The formation and secretion
of collagen molecule takes approximately 35 – 60 mins.
(transit time)
EXTRA CELLULAR EVENTS
• Procollagen mature collagen
• Pro pe ptid e se q ue nc e is re mov e d by procollagen
peptidases.
STEP 7: Cleavage of registration peptides in the extra
cellular space, by procollagen peptidases.
• The resulting molecule is collagen

Carboxy terminal
peptidase amino terminal
peptidase
• Fibrillar collagen so formed aggregates as ordered fibrils.
• I n these f ib rils, adjacent collagen molecules are
staggered by one fourth of their molecular length

• This quarter stagger arrangement gives tensile strength

to fibrils.
STEP 8: Self-assembly or polymerization of collagen
molecules form collagen fibrils.

STEP 9: Cross-linkage between adjacent collagen molecules

stabilizes the fibrils
 REGULATION

Mediator Major source Collagen synthesis

Growth factors Platelets, Macropages, Increases
PDGF,TGF-β, FGF,IGF Smooth muscle cells,
Epithelium
Serum
Cytokines/ M a c r o p h a g e s , Decreases
Lymphokines Lymphocytes
IL-1α β, IFN-γ, TNF-α Monocytes
Macrophages
Hormones Decreases
Glucocorticoids
Others Monocytes/ Decreases
PGE2 Macrophages
Excess collagen synthesis
1. Responses to cell injury
Deficient collagen synthesis
a. fibrous tissue repair
1. Nutritional deficiencies
b.parenchymatous organ
a. hypovitaminosis C
repair
b. zinc deficiency
i. pulmonary fibrosis
c. starvation
ii. cirrhosis
2. Glucocorticoid excess
iii. glom e r uloscle rosis /
3. Prostaglandins
interstitial fibrosis
4. Virus infection
2. Hypertrophic scar formation
3. Neoplasia
COLLAGEN DEGRADATION
• Two mechanisms for the degradation of collagen have
been recognised:
(1) The secretion by cells of enzymes that sequentially
d e grad e c o llage n and o the r matrix mo le c ule s
extracellularlv.
(2) The selective ingestion of collagen f ibrils by f ibroblasts
and their intracellular degradation
INTRACELLULAR PATHWAY
• Recognition of collagen fibers to be degraded
• Cleavage of fibrils
• Phagocytosis of cleaved fibrils

• Formation of phagolysosome
• Intracellular digestion by lysosomal enzyme like Cathepsin
 • Protoglycanase and Stromelysin remove the proteoglycans
around the collagen fibres and expose them to collagenase

Inactive collagenase (bound with inhibitor)

is secreted

Activating enzyme removes the inhibitor

Activated collagenase binds to fibrillar collagen

Collagen is split into 2 fragments (TCA & TCB)

Increased collagenase activity
a. acute inflammation
b. immune mediated cell
injury
c. mast cell degranulation
d. bacterial infection
e. tumor invasion
Increased susceptibility of
collagen
a. denaturation of collagen
i. tissue hyperthermia
ii. underhydroxylation of
proline
b. deficient cross-links
Deficient degradation
Decreased collagenase
activity
a. cirrhosis
b. scleroderma
c. osteopetrosis
Decreased susceptibility
of collagen
a. diabetes mellitus
b. hypertrophic scar
COLLAGEN IN GINGIVA

Gingival connective tissue contains collagen types I, III, IV, V,

VI, and VII.
Types I and III form the major collagen f ibers , which
occupy approximately 60% of the extracellular space.
Type I is organized into denser fibrils
Type III localized mostly as thinner f ibers and distributed
in reticular pattern are abundant beneath the epithelium
and around blood vessels.
Type IV is a component of the basal lamina of gingival
epithelium, blood vessels, and neural tissue.

Types V and VI are minor components found in association

with blood vessels, nerves, and subepithelial basement
membranes.

Ty pe V I h a s a l s o be e n s h o w n t o f o r m u n ba n d e d
microfilaments that bridge larger type I fibrils.

Type VII forms the anchoring f ibrils, which are part of the
subepithelial basement membrane
The collagen of gingival connective tissue turns over more
rapidly than that of skin and bone but more slowly than that
of the periodontal ligament.
New f ib roblasts are derived from the proliferation of
undifferentiated perivascular cells as well as by division of
differentiated fibroblasts.
COLLAGEN IN PERIODONTAL LIGAMENT

• The anchorage function is provided by collagen fibers.

• Classif ie d broadly into two groups, principal f ibers and

secondary fibers.

• Principal f ibers are dense collagenous bundles traversing

the periodontal space between tooth roots and alveolar
wall.

• Secondary f ibers are randomly oriented f ibrils located

between the principal fibers and investing nerves and blood
vessels. These fibers do not attach cementum or bone.
Collagen is the most abundant protein of ECM of the
periodontal ligament .

Type I collagen accounts for approximately 80% of the

total collagen content. It is the major component of the
principal fibers. And makes up the bulk of sharpey’s fibers.

Type III collagen, accounting for about 15% of the total

collagen protein, is preferentially localized on major f ibrils
and in reticular f ibers located around blood vessels and
peripheral nerves.
• Type VI is present in the pdl as f ine microf ibrils appearing
to interconnect cross-striated fibrils.

• Type V is believed to be associated with the cell surface

and to coat larger type III and type I fibrils.

• Type XII novel collagen believed to be involved in the

three-dimensional organization of the extracellular matrix.

• Type XIV is associated with major collagen f ibrils, but not

with microfibrils.
COLLAGEN IN CEMENTUM
Composed of predominantly type I and type III.
5% of type III collagen is accounted for the Sharpey’s
fibers that are a part of the periodontal ligament.
COLLAGEN IN ALVEOLAR BONE

Bone collagen is virtually insoluble in neutral salts. It is

only slightly soluble in dilute acid solutions.

The high degree of hydroxylation of lysine telopeptides

imparts the insolubility even after decalcification.

Two major crosslinks

hydroxylysinonorleucine

dihydroxylysinonorleucine
It contains type I collagen predominantly with the
molecular configuration of [α1 (I) α2 (I)].
The c o l l age n o f bo ne has l e ss d i gl yc o syl at e d
hydroxylysine than that of skin.
The ratio of glycosyl-galactosyl hydroxylysine to
galactosyl hydroxylysine is 0.47 in bone compared to
2.06 in skin
AGE CHANGES IN COLLAGEN:
• Increased rate of conversion of soluble to insoluble
collagen.
• Increased mechanical strength
• Increased denaturing temperature
• Increased thermal contraction
• Decreased water content
• Increased resistance to proteolytic enzymes
• Decreased level of acid mucopolysaccharide

All these causes increased content of collagen despite low

rate of synthesis
DISORDERS OF COLLAGEN
• Genetic Disorders
• Immunogenetic Disorders
• Secondarily Affected Collagen Metabolism Disorders
• Disorders Affecting Collagen Degradation
• Acquired Diseases
Genetic disorders Immunogenetic
Osteogenesis disorders
Imperfecta Lupus erythematosis
Ehlers Danlos Dermatomyositis
Syndrome Polymyositis
Marfan syndrome Scleroderma
Cutis Laxa – lax skin Severe pulmonary
Chondrodysplasia emphysema
Diseases are seen due to
basic presence of
anticollagen antibodies.
Disorders affecting Disorders due to collagen
collagen degradation –
metabolism –
Epidermolysis bullosa Homocystinuria
Rheumatoid inf lammatory Spondylo – epihysial
synovitis dysplasia
Alkaptonuria with
Acquired diseases ochronosis
Chronic inf la mmatory diseases and f ib roses are most
common types
Eg –submucous fibrosis, progressive systemic sclerosis
Caused by interaction of f ibroblasts with various cytokines
liberated in plasma and damaged tissues.
 Gene or Enzyme
Disease

C0LIAI C0L1A2 Osteogenesis imperfecta,

Osteoporosis

Ehlers-Danlos syndrome type V autosomal dominant

C0L2A1 Severe chondrodysplasias

Osteoarthritis

C0L3A1 Ehlers-Danlos syndrome Type IV

COL4A3-COL4A6 Alport syndrome (including both autosomal and X-linked

forms)

Lysyl hydroxylase Ehlers-Danlos syndrome Type VI

C0L7A1 Epidermolysis bullosa,

COL10A1 Schmid metaphysial chondrodysplasia

OSTEOGENESIS IMPERFECTA
• Abnormality in type I collagen. Inherited disorder. type 1-
IV.
• -Extreme fragility of bone and proneness to fracture

-Pale blue sclera,deafness -Abnormal shape of skull and

laxity of ligaments
• Type IV is associated with dentinogenesis imperfecta.
• Abnormal conversion of fetal to mature collagen with
defective intermolecular crosslinkage.
EHLER DANLOS SYNDROME
• Due to tenascin X defeciency or lysyl hydroxylase
• Genetic defect in collagen and connective tissue synthesis
and struc ture . type I - VI I I , Type VI I I asso c iate d with
periodontal findings
• Hyper extensibility of joints, fragility of skin(rubberman) and
blood vessels
• Excessively fragile oral mucosa with easy bruising
• E asy ble e d ing o f gingival tissue s(to o thbrushing)
Hypermobility of TMJ with repeated dislocations .
 SCLERODERMA
• It is a systemic connective tissue disease, autoimmune.
• Increased collagen deposition is a characteristic feature.
• Begins on face,hands and trunk.
• organs involved are GI tract, lungs, CV system, renal system,
musculoskeletal system and CNS.
• Skin takes a waxy appearance due to hardening and
cannot be wrinkled giving masklike appearance to face and
claw like appearance to the hands
• Variant is CREST syndrome.
• Tongue, soft palate and larynx are commonly involved
(mild edema-atrophy-induration).
• Lips become thin ,rigid and partially closed.
• Limitation in mouth opening.
• Gingival tissues are pale and unusually firm.
• They lead to changes similar to Sjogren`s syndrome
• R ad io graphic ally the re is ge ne ralize d wid e ning o f
periodontal ligament ( two or four times), resorption of angle
and condyle of mandible
EPIDERMOLYSIS BULLOSA
• It is a dermatologic disease with bullae and vesicles on
skin and mucous membrane.
• These bullae occur spontaneously or after minor trauma
on feet, buttocks, scapulae, elbows, fingers, occiput.
• Oral bullae are preceeded by white patches or spots of
mucous membrane.
• Bullae initiated by nursing or simple dental procedure.
• They heal with scar formation, with obliteration of the
sulcus and restriction of tongue.
• Rudimentary, hypoplastic teeth, with denuded enamel
SCURVY
• Vitamin C is necessary for hydroxylation of proline to
hydroxyproline thus is defective collagen produced a
• Petechiae are commonly seen about hair follicles and skin
of lower extremities.
• Chronic gingivitis is early manifestation.
• Interdental and marginal gingiva becomes bright red with
swollen, smooth, shiny surface
• In severe scurvy gingiva is ulcerated and bleeds easily
• This bleeding may occur into periodontal ligament
followed by loss of bone-loosening of teeth-exfoliation.
THERAPEUTIC APPLICATIONS
• Collagen is well established as a safe and effective
biomaterial and was one of the f irst to be used in medical
products
• Before the era of synthetic polymers, collagen sutures
were used as a standard material in surgical procedures, a
prac tic e whic h c an be trac e d bac k to the A nc ie nt
Egyptians
Properties of collagen making it suitable to be used as
biomaterial.
– Natural component of tissues hence tolerated.
– Weak immunogenic, possessing favorable tissue
response.
– Malleable
– Semi-permeable, allowing nutrient passage and gas
exchange.
– Possess haemostatic properties, through its ability to
aggregate platelets.
– Supports cell proliferation is a lattice structure and cell
binding domain.
– Facilitates early wound stabilization and maturation.
– Chemotactic for fibroblasts.
– Promotes cell migration; leading to promote primary
closure or increase barrier exposure.
– Absorbed naturally, if replaced by host tissue, tissue
volume can be increased.
Applications of collagen as a biomaterial
• To repair tissues such as bone, tendon, ligament, skin,
vascular and connective tissues.
• For use as sealant, implant coating, adhesion barrier and
tissue engineering devices.
• Drug delivery applications: to develop scaffolds for
delivery of genes, cell, growth factors, anesthetics,
analgesics, antibiotics etc.
• Tissue augmentation: For use in plastic surgery For use in
collagen coating of grafts
• To enhance blood coagulation and platelet activation
• To enhance durability of allograft tissues .
• Can be used for the generation of bone substitutes, wound
dressings, nerve regeneration, artificial skin.
• For use as a research tool to study diseases such as
diabetes and aging, and to evaluate drugs.
• Collagen used for medical devices is derived from several
animal sources including bovine skin, tendon, intestine, or
sheep intestine. Isolation and purif ic ation follows one of
two ways.
1. The first is enzymatic preparation of soluble
collagen
2. Chemical extraction of fibrillar collagen from
collagenous tissue.
Following isolation and purification, collagen is processed
by several means to manufacture gels, sponges, filaments,
membranes, etc. for specific applications.
Increased cross-linking results in
Decreased solubility
Decreased water absorption
Decreased susceptibility to enzymatic degradation
Increased tensile strength
Increased biodegradation time and
Decreased immunogenicity
Limited tissue toxicity
I. In guided tissue regeneration
II. Drug delivery applications

To develop scaffolds for delivery of genes, cell, growth

factors, anesthetics, analgesics, antibiotics etc.

a) Collatamp G

It is an implantable

Type-I collagen sponge

Impregnated with 2.0 mg/cm2 of gentamicin sulfate

b) Periodontal plus AB

Contains tetracycline hydrochloride 2mg in 25mg collagen

c) INFUSE™ Bone Graft
and InductOs™
Collagen sponges have been selected as the preferred
matrix for local delivery of RhBMP-2 directly to the bone
defect, serving to prolong the residence time of the
protein and, in some instances, as support for invading
host osteoprogenitor cells
III. Localised delivery to blood vessels and nerves
a) Ark Therapeutics Ltd has developed a biodegradable
collagen collar, (Trinam®) which uses the device to
deliver a vascular endothelial growth factor (VEGF) gene
and is currently undergoing clinical trials to prevent the
blocking of veins and arteries that frequently occur after
vascular surgery.
b) Collagen Matrix, Inc. has patented
(Li et al. , 2003) and is developing collagen devices for
peripheral nerve regeneration, including the localised
delivery of bioactive molecules (such as growth factors)
to bridge long nerve defects.
IV. To enhance blood coagulation and platelet activation
Collagen is a natural haemostat and a wide variety of
collagen-based products are used in surgery and dentistry
to control excessive bleeding or haemorrhage.

Oxycel
E.g: Gelfoam

Surgicel absorbable Collacote, Collatape

 Cosmetic procedures

• Collagen finds extensive use in cosmetic procedures.

• The injection places collagen directly beneath the lines or
wrinkles, which helps to smooth the overall appearance of
the skin at that point..
• Is also used to regenerate skin tissue among burn victims
Collagen skin cream

• The companies claim that such products will improve the

strength and vitality of the existing collagen structure in
the skin.
• lack sufficient scientific evidence to support the claims.
• The creams may, however, function as moisturizers, which
do benef it skin health and appearance, meaning the
creams do provide some value.
• Many people choose collagen tablets to help fend off
wrinkles and skin issues, but the pills can also be very
helpful in relieving joint and muscle stiffness and pain.
• It is also believed that the tablets will help with muscle mass
, hair and nails.
• C o l l a ge n i nd uc t i o n, a m e d i c a l pro c e d ure w he re a
dermaroller is applied to the forehead, stimulates the body
to produce more collagen and elastin, thus decreasing
forehead wrinkle lines. Administration approved the use of
Evolenc e, a c ollagen-based d ermal f il ler, to c orrec t
nasolabial folds
 Heart valves
Creating artif ic ial heart valves represents another
proposed medical use of collagen, suggests that collagen
constructs might be able to replace faulty heart valves in the
future. As of 2005, the technology remained unready for
human trials..
Gelatin
• Gelatin represents the major industrial application of
collagen.
• I ts use s inc lud e fo o d pro d uc ts and c apsule s fo r
medication.
Food sources of collagen
• Vegetable sources : pinto beans, kidney

beans, black beans, navy beans, peanuts,

tomatoes , asparagus, purple cabbage
• Nuts and seeds macadamia nuts, brazil nuts, pumpkin
seeds, sesame seeds and sunflower seeds
• Milk, cheese, yogurt and cottage cheese into the diet to
aid in collagen production, Eggs, meats like chicken, beef,
turkey, fish
• Strawberries, oranges, grapefruits, lemons, blackberries,
black currants, blueberries, plums, elderberries, purple f igs,
purple grapes and papayas
CONCLUSION

Collagen has ubiquitous distribution and unique

structure and function in maintaining the structural and
functional integrity of the extracellular space throughout
the body and in particular the periodontium. Also its
properties makes it as a very good biomolecule to be
used in periodontal regeneration which is the goal of
periodontal therapy.
 Collagen has been used extensively for manufacture of
biomedical devices because of its biologic and physical
properties, and ample availability.
Also it has various industrial applications. Many clinical
researches and trials have been undergoing for the advanced
uses of collagen.
Thus ,
“Proves to be one the most important proteins in your entire body”
REFERENCES
• Oral histology: Development structure and function ; A.R.
Tencate: 7th Edition
• Harper’s illustrated biochemistry ; 26th Edition
• Oral cells and tissues ; P.R. Garant
• Clinical Periodontology ; Carranza: 10th Edition
• A textbook of Oral Pathology ; Shafer : 5th Edition
• Biochemistry and oral biology: A.S.Cole,J.E.Eastoe; 2nd edtn
• Devices for periodontal regeneration. Periodontology 2000,
Vol. 19, 1999, 59-73

• Collagen membranes : A Review ;J Periodontol 2001;72:215

Thank you