TISSUE REPAIR AND

HEALING
Dr Hira Faisal
Senior lecturer,
Department of Pathology
BUMDC
  To understand the concept of regenration and repair
 To discuss in detail the process of tissue repair
 To discuss different factors affecting wound healing

OBJECTIVES  To discuss in detail the process of cutaneous wound healing

 To understand the various complications that arise from wound
healing
 Repair, sometimes called healing refers to the
restoration of tissue architecture and function after an injury.
TISSUE REPAIR • Repair of damaged tissues occurs by two types of reactions:
AND HEALING 1. Regeneration.
2. Connective tissue deposition (scar formation).
 Regeneration: is complete
restitution of lost tissue
components identical to those
removed or killed by proliferation
of residual (uninjured) cells and
maturation of tissue stem cells.
Connective tissue deposition
(scar formation): If the injured
tissues are incapable of
regeneration, or if the tissue is
severely damaged, repair occurs by
the deposition of connective tissue.
 Regeneration occurs for
example, in the rapidly
dividing epithelia of the skin
and intestines, and in some
parenchymal organs, notably
the liver.
Scar formation takes place in
fibrosis of the lungs, liver,
kidney and in Myocardial
Infarction
 2. Proliferation and
migration of
Components of wound
1. Inflammation. parenchymal
healing
and connective tissue
cells.

3. Formation of 5. Acquisition of
4. Wound contraction.
granulation tissue. wound strength.
 • Both regeneration and scar
formation contribute in
Tissue Regeneration
varying degrees to the
ultimate repair.

• Both processes involve the

• The cell proliferation in
proliferation of various cells,
regeneration and repair is
and close interactions
driven by growth factors
between cells and the
(VEGF, TNF, PDGF, TGF).
extracellular matrix (ECM).

Tissue proliferative activity
1.Continually dividing cells
(labile tissues):These cells
proliferate through-out life.
Epithelium of the skin, GIT
and cells of bone marrow.
2.Quiescent cells (Stable
tissue):Have a low level of
replication. Cells from these
tissue can undergo rapid
division in response to stimuli.
parenchymal cells of liver and
kidneys.
3.Non-dividing (permanent
cells): Cells that can not
undergo mitotic division in the
postnatal life. Neurons and
cardiac muscle cells.
 • Granulation tissue is the • The term granulation
hallmark of healing. tissue derives from its
Granulation tissue Granulation tissue pink, soft, granular
progressively invades the appearance seen an area of
site of injury. going wound healing.
 • Granulation tissue is
Granulation tissue
composed of:

ii. new thin-walled, delicate

i. the proliferation of iii. admixed inflammatory
capillaries(angiogenesis), in a
fibroblasts cells, mainlymacrophages.
loose extracellularmatrix.
 • Healing of skin wound is
• Based on the nature and
a process that involves
size of the wound,
both epithelial
Healing of skin wound the healing of skin
regeneration and the
wounds occurs by first or
formation of connective
second intention.
tissue scar.
 • When the injury involves
only the epithelial layer and • It is the process of healing of
the principal mechanism of a clean, uninfected surgical
Healing by first intension
repair is epithelial regeneration incision approximated by
it is called primary union or sutures.
healing by first intention.
 Incision causes only focal
disruption of epithelial
basement membrane continuity The repair consists of three
and death of relatively few connected processes:
epithelial and connective tissue
cells.

proliferation of epithelial and and maturation of the

inflammation,
other cells, connective tissue scar.

which results in the formation
of a blood clot which
contains fibrin, fibronectin,
and complement proteins.
Wounding causes the rapid
activation of coagulation
pathways,
It serves to stop bleeding ,acts
as a scaffold for migrating cells
Release of VEGF leads to
increased vessel permeability
and edema. As dehydration
occurs at the external surface,a
scab covering the wound is
formed.
 Within 24 hours, neutrophils a
at the incision margin, migrate
towards the fibrin clot and
release proteolytic enzymes that
begin to clear the debris.
Within 24 to 48 hours,
epithelial cells from both edges
migrate and proliferate along
the dermis, depositing basement
membrane components.
Basal cells at the cut edge of
the epidermis begin to show
increased mitotic activity.
The cells meet in the midline
beneath the surface scab,
yielding a thin but continuous
epithelial layer that closes the
wound

By day 3, neutrophils have
been largely replaced by
macrophages, and
granulation
tissue progressively
invades the incision space. deposition.Collagen fibers
Macrophages are key
cellular constituents
of tissue repair, clearing
Epithelial cell
extracellular debris,
proliferation continues,
fibrin, and other foreign
forming a covering
material, and promoting
approaching the normal
angiogenesis and ECM
thickness of the epidermis.
are now evident at the
incision margins.
 By day 5, neovascularization
Migration of fibroblasts to the site
reaches its peak but new vessels
of injury is driven by
are leaky, allowing the passage
chemokines, TNF, PDGF, TGF-β,
of plasma proteins and fluid into
and FGF which proliferate esp
the extravascular spacemaking
under influence of YNF and IL 1.
GT edematous

Epidermis recovers its normal

thickness as differentiation of They produce ECM proteins, and
surface cells yields a mature collagen fibrils to bridge
epidermal architecture with the incision.
surface keratinization.
During the second week, there
is continued collagen accumulation and
fibroblast proliferation.

The process of “blanching”

begins,accomplished by increasing
collagendeposition within the
incisional scar and the regression of
vascular channels
By the end of the first month, the scar
comprises a cellular connective
tissue largely devoid of inflammatory
cells andcovered by an essentially
normal epidermis.

The tensile strength of the wound

increases with time.
 Healing by second intention

When cell or tissue loss is

more extensive like in large The repair process in second
Healing by second intention
wounds, abscesses, intension involves a
is also known as healing by
ulceration, and ischemic combination of regeneration
secondary union.
necrosis (infarction) in and scar formation.
parenchymal organs.
 Healing by Second Intention

The inflammatory reaction is more

When cell or tissue loss is more
extensive, such as in large wounds,
abscesses, ulceration, and ischemic
necrosis (infarction) in
parenchymal Organs
intense, there is development of
abundant granulation
tissue, accumulation of ECM and
formation of a large scar, and
wound contraction by the action of
myofibroblasts.
 there is more exudate and Inflammation is more
the fibrin clot is larger, and
necrotic debris intense

Consequently, large
More amount of
defects have a greater
granulation tissue is
potential for secondary,
needed resulting in greater
inflammation-mediated,
mass of scar tissue
injury.
 At first a provisional matrix
containing fibrin, plasma fibronectin,
Ultimately, the original granulation
and type III collagen is 01 tissue scaffold is converted into a
formed,replaced by a matrix
pale, avascular scar,
composed primarily of type I collagen
in about 2 weeks.

02

The epidermis recovers its normal

thickness and architecture. By the end
of the first month, the scar is made up
of acellular connective tissue devoid
of inflammatory infiltrate, covered by
intact epidermis.
 It helps close the wound
by decreasing the gap
Within 6 weeks, large skin
between its dermal edges
Wound contraction defects may be reduced to
and by reducing the
generally occurs in large 5% to 10% of their
wound surface area there
surface wounds. original size, largely by
is formation, at the edge of
contraction.
the wound, of a network
of myofibroblasts,
PRIMARY INTENTION
Inflammatory reaction is
less marked.
No wound contraction.
Margins are opposed together
Minimal tissue damage
Minimal bleeding
Heals quickly
Small scar
SECONDARY INTENTION
Intense inflammation.
More bleeding
Much Granulation tissue formation
Gap persists between margins
Marked damage of tissues
Takes time to heal
Large Scar
 Factors influencing wound healing
1. Nutritional status: Protein
deficiency and vitamin C
deficiency inhibit collagen
synthesis and delay wound
healing.
Systemic factors:
4.Hormones: Glucocorticoids
2.Metabolic status: DM is 3. Circulatory status, poor
have anti- inflammatory effects
associated delay in wound perfusion: Inadequate blood
and inhibits collagen synthesis
healing. supply impair wound healing.
causing delay
 Factors influencing wound
healing
Local factors:
• 1. Infection (one of the most important cause of delay in healing).
• 2.Mechanical factors (increased local pressure, high mobility delays healing).
• 3. Foreign bodies (splinter, steel, glass delays healing).
• 4. Size and shape of wound (clear cut surgical wound heals quickly).
• 5. Location of the wound (wound in the face heals quickly)
COMPLICATIONS OF WOUND HEALING
• Complications of wound healing are grouped into three categories:

i. Deficient scar formation.

ii. Excessive scar formation.

iii. Exuberant granulation tissue formation

iv. Formation of contractures

 Wounds ulceration is due to
Wound dehiscence is common
inadequate vascularization.
DEFICIENT SCAR can lead to two types of after abdominal surgery and is
Example lower extremity
FORMATION complications: due to increased abdominal
wounds in with
pressure.
atherosclerosis.

1.Dehiscence or rupture of a
2. Ulceration.
wound.
Complications of wound healing
• Excessive scar formation can give rise to:
• (1) hypertrophic scar
• (2) keloids.

• The accumulation of excessive amounts of collagen give rise

to a hypertrophic scar.

• If the scar tissue grows beyond the boundaries of original

wound and does not regress, it is called keloid.
KELOID
 Excessive granulation must be
EXUBERANT GRANULATION removed by cautery or surgical
TISSUE excision to allow re-
epithelialization

Exuberant granulation is the

formation of excessive amounts of
granulation tissue, which protrudes
above the level of the surrounding
skin and blocks re-epithelialization
(proud flesh).
 Wound Contracture

An exaggeration of
contraction of wound gives Contractures are commonly
Common areas affected
rise to contracture and seen after serious burns
palms, the soles and the
results in deformities of the which compromise
anterior aspect of the thorax.
wound and the surrounding movement of joints.
tissues.
 REMODELING OF
CONNECTIVE TISSUE

Scar modified and remodeled

The outcome of the repair is by an enzyme called matrix
The connective tissue in the
influenced by a metalloproteinases (MMPs)
scar continues to be modified
balance between synthesis and produced by a variety of cell
and remodeled.
degradation of ECM proteins. types (fibroblasts,
macrophages, neutrophils.
THANK YOU