Regeneration

• In human beings regeneration occurs only as a

compensatory growth e.g
• Regeneration of liver
• Removal of one kidney causes enlargement of
the other
• The other regenerative activity taking place is
the continuous replenishment of blood cells,
epithelial cells of GIT and epidermal cells of
skin
 Repair
• Repair refers to replacement of destroyed
tissue by living tissue

• This replacement or repair of a damaged

tissue may be done in two ways:

1. Regeneration
2. Healing
 Healing

• Healing is defined as the process whereby lost

tissue is replaced by fibrous tissue or scar.
• This involves regeneration as well as scar
formation e.g
1) Skin healing :
• When only epidermis is damaged – heals by
regeneration
• When dermis is also damaged – Heals by scar
formation
 Healing

2) Myocardial infarction:
• Surrounding cells do not have capacity to
regenerate
• Healing by scar formation
3) Pericarditis :
• Inflamed pericardium heals by fibrosis
• Adhesions occurs between two layers of
pericardium and constrict
• Constriction of heart takes place- known as
Constrictive pericarditis
 Healing

4) Gastric ulcer:
Heals by fibrosis , causing stricture and
deformities e.g pyloric stricture and hour
glass deformity
5) Cirrhosis of liver:
Necrosed hepatocytes are replaced by fibrosis

Organisation : During healing lost tissue is

replaced by granulation tissue and finally by
fibrous tissue to form scar. This is termed as
organisation
 Factors for healing
1) Proliferative activity of the tissue and stem
cells

2) Growth factors

3) Mechanism of cell growth

4) Cell cycle

5) Cell-matrix interaction
Proliferative activity of the tissue and stem cell
Depending on proliferative ability tissues are
divided into 3 types:
1. Labile tissue : continuously dividing cells

2. Stable tissue : divide at slow rate

3. Permanent tissue : non-dividing cells

 Labile Tissue

The cells continuously proliferate throughout life

They continuously replace the cells which are
regularly lost or destroyed e.g
• Surface epithelial cells of skin, GIT, urinary
bladder etc.

• Bone marrow cells

• Stem cells
 Stem Cells

• These cells have unlimited capacity to

proliferate and differentiate into various types
of cells
• Characteristics of stem cells:
1. Unlimited self-renewal and proliferation
capacity
2. Asymmetric replication:
One of the daughter cell retains self- renewing
(stem cell) character while the other can
differentiate
 Types of stem cells

1) Embryonic stem cells:

These are pluripotent cells which give rise to all
the different tissues of the body
2) Adult stem cells:
They have the capacity to differentiate into
different adult stem cells
Sites of adult stem cells: 1) Bone marrow 2)Base
of colonic crypts 3) Hair follicles 4) Limbus of
cornea
 Stable Tissue
• Also called quiescent tissue
• They divide at slow rate normally
• They divide at fast rate when stimulated by
injury
Example: Hepatocytes ( regeneration of liver),
renal tubular cells, fibroblasts, smooth muscle
cells and leukcytes
 Permanent Tissue

They are non-dividing in postnatal life e.g

1) Neurons:
Neurons of the brain cannot be replaced
Neurons can be formed from stem cells
2) Skeletal muscles:
Skeletal muscles cannot divide but can be
regenerate from stem cells
3) Cardiac muscle:
Injury to cardiac muscle is replaced by fibrosis
e.g Myocardial infarction
 Growth Factors
The major growth factors involved in the process
of healing are:
1. Epidermal growth factor- EGF
2. Transforming growth factor alpha – TGF-a
3. Platelet derived growth factor- PDGF
4. Fibroblast growth factor- FGF
5. Transforming growth factor beta- TGF-b
6. Vascular endothelial growth factor- VEGF
7. Cytokines
 Wound contraction
• Starts after 2-3 days and completes by about
14th day of injury
• Wound contraction occurs due to granulation
tissue formation
• Granulation tissue is composed ofproliferating
small blood vessels and fibroblasts
• Fibroblasts contract resulting in wound
contraction
• Although wound contraction is useful, some
complications arises e.g
1.Strictures : stomach , intestine, fallopian tube
2. Contracture : burns causing impaired mobility
 Granulation Tissue
• Granulation tissue consists of proliferating
small blood vessels and fibroblasts
• Granuloma is a collection of epithelioid cells
and histiocytes e.g tuberculosis
• Organisation : Replacement of necrotic tissue,
inflammatory exudate , thrombus or blood
clot by granulation tissue is called organisation
• Organisation occurs in inflammation,
pneumonia, wound healing, thrombus and
infarct
 Wound healing in the skin
• Two types of healing process may be seen in
the skin according to the type of wound
1. Healing by first intention or primary union
This occurs in clean incised wound with edges in
apposition
2. Healing by second intention or secondary
union
This occurs in wounds with separate edges
The basic mechanism of healing is same for both
but the quantity of scarring differs
 Healing by first intention

• Also known as primary union

• Occurs in clean uninfected surgical incision
Changes taking place in first intention
1. Initial effect
2. 24 hours
3. By third day
4. By fifth day
5. During second week
6. End of first month
1. Initial effect
• Limited cell death
and disruption seen

•Narrow incisional
space filled with
blood clot

•Clot dries up and

forms scab
 2) 24 hours
• Within 24 hours the
polymorphs appear
at the margins of the
incision
• Epithelial cells from
opposing epidermis
migrate into the
wound
• Migrating cells fuse
in the middle forming
epithelial layer that
covers wound surface
 3) By third day
• Neutrophils are
replaced by
macrophages
•Granulation tissue
starts forming
• Laying down of
collegen fibers starts
in the margins
• Epithelial layer
formed start
thickening
By fifth day
• Granulation tissue
completely fills up
wound space
• Collagen laying
down bridges the
incision gap
• Epithelial cell
proliferation is
complete, restoring
the normal thickness
5) During second week

• Inflammatory cells,
edema and increased
vascularity disappear

• Increased collection
of collagen and
fibroblasts

• This leads to scar

formation
6) End of first month
• Scar is formed
which is covered by
epidermis
• Permanent loss of
skin appendages in
the scar area
• Strength of scar
increases and takes
months to reach
maximum strength
 Healing by secondary intention
• Also called as secondary union
• Takes place when there is excessive tissue loss
• Granulation tissue is the main bulk which
repairs the wound
Changes taking place in secondary intention:
1. Initial effect
2. Wound contraction
3. Epithelial cell migration
4. Granulation tissue formation
5. Regeneration of epidermis
6. Scar formation
 Factors influencing healing and repair
• There are multiple factors delay wound healing.
They are: a) Local factors b)General factors
Local Factors
1. Blood supply:
a) Varicose ulcers: There is stagnation of blood and
poor supply
b) Bedsores: Pressure points leads to poor blood
supply
c) Chronic inflammation: Thickening of vessel wall
causes poor blood supply
d) Old age: Atherosclerosis in old age leads to poor
blood supply
 Factors influencing healing and repair

2) Movement: Movement causes delayed

healing e.g wound in the corner of mouth
and fracture of mandible
3) Bony adhesions: Adhesion of wound edges
to bony surface delays healing
4) Radiation: Ionising radiation causes
destruction of vessels and delayed healing
5) Local temperature: Hyperthermic
environment enhances wound healing
Factors influencing healing and repair- GeneralFactors
1. Infection and inflammation
2. Nutritional deficiencies: deficiency of Vitamin
C , protein or zinc delay wound healing.
Vitamin C is needed for collagen synthesis
3. Age : Healing is slower in old age
4. Diabetes mellitus: Healing delayed due to its
effect of hyperglycaemia
• Delayed healing in tooth extraction and
suture wound in diabetes
5. Hormones: Corticosteroids delay wound
healing by inhibiting collagen synthesis
 Complications of wound healing
1) Hypertrophic scar
2) Keloid formation:
• Excessive laying down of collagen and ECM result
in raised area of scar formation
• When these are localised at the site of injury and
do not progress , they are called hypertrophic scar
• When these scar spreads beyond injury site and
recurs after excision, they are called keloid.
• Clinically they are raised, itchy and tender
• Hypertrophic and keloid scars do not occur in oral
cavity
 Complications of wound healing

3 ) Bursting of wound: e.g bursting of abdominal

wound called burst abdomen
4) Wound contraction: e.g severe contraction can
cause deformities in stomach and strictures in
intestines
5) Pigmentation : Healing in skin causes hyper or
hypopigmented areas e.g lichen planus scar is
blackish in colour
 Complications of wound healing

6) Dry socket: Alveolar osteitis

Dry socket is a focal osteomyelitis of the bone
around the socket of the extracted tooth .
This is commonly seen in
• Extraction of an impacted bone
• Traumatic extraction
• Radiotherapy
• Women taking oral contraceptives
 Complications of wound healing
• Pathogenesis of dry socket:
Following dental extraction cavity gets filled with
blood clot
In dry socket clot gets destroyed exposing bone.
Destruction of clot occurs by:
1. Protelytic enzymes of bacteria
2. Plasminogen released by injured bone and
soft tissue
Morphology: Inflammation and sequestrum seen
Clinical picture: severe throbbing pain, foul
smell , fever occurs
 Healing in different organs
1) Bone: Healing takes place by laying down of
woven bone by osteoprogenitor cells and
cartilage by chondroblasts.r
The newly formed tissue is called callus.
The bony callus joins the fractured ends.
2) Liver: Liver has the highest capacity to
regenerate.
The hepatocytes along with fibrous tissue laid down
by stellate cells of liver.
This gives a multinodular appearance called
cirrhosis
 Healing in different organs
3) Central nervous system:
Brain has limited regenerating capacity.
Necrosed tissue is replaced by proliferating
neuroglia to form glial scar (gliosis)

4) Heart:
Cardiac muscles do not show any regeneration.
Necrosed cells are replaced by fibrosis (scar) called
myocardial infarction