Wound Healing

Cutaneous Wound Healing

Dr.CSBR.Prasad, M.D.
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Cutaneous Wound Healing
Divided into three phases:

1. Inflammation
2. Proliferation &
3. Maturation
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Cutaneous Wound Healing
Inflammation: Platelet adhesion and
aggregation and the formation of a clot in the
surface of the wound, leading to inflammation
Proliferative phase there is formation of
granulation tissue, proliferation and migration
of connective tissue cells, and re-
epithelialization of the wound surface
Maturation involves ECM deposition, tissue
remodeling, and wound contraction
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Healing by primary union or
by FIRST INTENTION
Death of a limited number of epithelial and
connective tissue cells
Minimal disruption of epithelial basement
membrane continuity
Formation of a relatively thin scar
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Healing by primary union or
by FIRST INTENTION
Wounds with opposed edges
Clean / sterile wounds
Example:
Surgical incision
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Healing by secondary union or
by SECOND INTENTION
Large defects cause extensive loss of cells and
tissue
More intense inflammatory reactions
Formation of abundant granulation tissue
Extensive collagen deposition
Formation of a big scars
Contractures
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Healing by secondary union or
by SECOND INTENTION
Wounds with unopposed margins
Gaps in tissue due to substantial loss
Infection / foreign bodies
Examples:
Crush injury
Infected wounds
Burns
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Crush injury
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Crush injury and skin grafting
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However, the basic mechanisms of healing by
primary (first intention) and secondary
(second intention) union are similar
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The most distinct feature that
differentiates Primay & Seconday
wound healing is
Wound contracture
That is seen in healing by second intention
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Events in wound healing
Blood clot formation - immediate
Neutrophil migration 24hours
Proliferation of epithelia at the edge 24-48hrs
Deposition of BM 24-48hrs
Scab formation 24 hrs
Macrophage entry 3
rd
day
Granulation tissue formation 5
th
day
Collagen deposition 5
th
day two weeks
Wound strengthening may take months
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Growth Factors and Cytokines Affecting Various
Steps in Wound Healing
Action Factors
Fibroblast migration /
replication
PDGF, EGF, FGF, TGF-,
TNF, IL-1
Keratinocyte replication HB-EGF, FGF-7, HGF
Angiogenesis VEGF, Angiopoietins, FGF
Collagen synthesis TGF-, PDGF
Collagenase secretion PDGF, FGF, TNF; TGF- inhibits
Monocyte chemotaxis Chemokines, TNF, PDGF, FGF, TGF-
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Blood clot
Wounding causes the rapid activation of coagulation
pathways
Formation of a blood clot on the wound surface
Clot contains entapped red cells, the clot contains
fibrin, fibronectin, and complement components
The clot serves to stop bleeding and also as a scaffold
for migrating cells, which are attracted by growth
factors, cytokines and chemokines released into the
area
Dehydration occurs at the external surface of the clot,
forming a scab that covers the wound
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Neutrophils
Within 24 hours, neutrophils appear at the margins
of the incision
They release proteolytic enzymes that clean out
debris and invading bacteria

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Formation of Granulation Tissue
The hallmark of tissue repair: Formation of
granulation tissue
Granulation tissue consists of: proliferating
Fibroblasts and vascular endothelial cells which
occurs in the first 24 to 72 hours of the repair
process
The term derives from its pink, soft, granular
appearance on the surface of wounds
Characteristic histologic feature : Angiogenesis and
the proliferation of fibroblasts

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Formation of Granulation Tissue
These new vessels are leaky, allowing the passage of
plasma proteins and fluid into the extravascular
space
Granulation tissue progressively invades the incision
space
By 5 to 7 days, granulation tissue fills the wound area
and neovascularization is maximal
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Granulation tissue
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Granulation
tissue
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Omphalocele covered by granulation tissue
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Accumulation of collagen 2
nd
week
Reduced number of leucocytes, edema
Regression of vascular channels
Accumulation of collagen
Progressive blanching


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Progressive accumulation of collagen
SCARRING
Cellular connective tissue
No inflammatory cells
Complete epithelialization of the surface
Absence of adnexal structures
Progressive increase in tensile strength of
wound


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Healing by secondary union or
by SECOND INTENTION
Large tissue loss
More intense inflammatory reaction
More granulation tissue
More fibrosis / collagen substantial scar
Wound contracture
Thin epidermis
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Granulation tissue & Scar tissue
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Wound strength
How log it will take for the wound to attain
maximal strength?
When sutures may be removed?
At the end of 1
st
week 10% of strength of
unwounded skin
By 3
rd
month 70-80% of strength of
unwounded skin
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Factors influencing wound healing
Systemic factors
Nutrition
Metabolic status
Circulatory status
Hormones

Local factors
Infections
Foreign bodies
Mechanical factors
Size / Location
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Complications of
cutaneous wound healing
May arise from abnormalities in basic
components of repair process:
1. Deficient scar formation
2. Excessive of repair components
3. Contractures
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Complications of
cutaneous wound healing
1. Deficient scar formation
Inadequate formation of granulation tissue or
assembly of scar may result in:
Dehiscence
Ulceration
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Incisional
hernia in
ED-Syndrome
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Complications of
cutaneous wound healing
1. Deficient scar formation
2. Excessive of repair components
Hypertrophic scar
Keloid
Proud flesh (exuberant granulation tissue)
Desmoids / aggressive fibromatosis
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Hypertrophic scar after surgical sutures
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Hypertrophic scar after burns
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Scar Keloid
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Scar Keloid
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Keloid
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Complications of
cutaneous wound healing
1. Deficient scar formation
2. Excessive of repair components
3. Contractures
Exaggeration of contracture results in deformities
Eg: After serious burns
Contractures prone areas:
Palms
Soles
Anterior thorax
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Wound Healing
Healing of Fracture
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Fracture
A fracture is a discontinuity of bone usually
due to trauma
It's often associated with soft tissue injury
(e.g. hemorrhage, necrosis, tearing of muscle,
tendon, ligaments, nerves and vessels)

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Healing of Fracture
There are three
processes involved
in the healing of
fractures:
Inflammatory
reparative and
remodelling phases
6 stages:
the hematoma stage
inflammatory stage
formation of
granulation tissue
soft callus
'hard' callus, and
remodelling


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or
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Hematoma Stage:
Hemorrhage, clot formation - within hours
This picture shows a sagittal section of a fractured humerous. It is clear this is
recent fracture because there is a large haemtoma and no evidence of
primary callus fomation
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Inflammatory Stage:
Begins within 48 hours, inflammatory cells appear.
Organization and resorption of clot.
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Granulation Tissue:
From 2 - 12 days. Presence of mesenchymal cells,
fibroblasts, new capillaries
Soft Callus:
One week to several months. Callus grows and bridges the
fracture site; cartilage and trabelcular bone laid down.

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Hard Callus:
One week to several months. When callus has sealed
the bone ends. Trabecular bone.
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Remodelling:
Continues for several months.
Reorganization of bone; original cortex restored
Fracture healing rates are:
Faster in the young than the old
Slower in the lower limb than the upper limb
Faster in spongy bone than compact bone

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Systemic Factors Affecting
Fracture Healing
Age: Young patients heal rapidly and have a remarkable ability
to remodel and correct angulation deformities. These abilities
decrease once skeletal maturity is reached
Nutrition: A substantial amount of energy is needed for
fracture healing to occur. An adequate metabolic stage with
sufficient carbohydrates and protein is necessary
Systemic Diseases: Diseases like osteoporosis, diabetes, and
those causing an immunocompromised state will likely delay
healing. Illnesses like Marfans syndrome and Ehlers-Danlos
syndrome cause abnormal musculoskeletal healing
Hormones: Thyroid hormone, growth hormone, calcitonin,
and others play significant roles in bone healing.
Corticosteroids impede healing through many mechanisms
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Local Variables Affecting
Fracture Healing
Type of bone: Cancellous (spongy) bone fractures are usually more stable, involve greater
surface areas, and have a better blood supply than do cortical (compact) bone fractures.
Cancellous bone heals faster than cortical bone.
Degree of Trauma: The more extensive the injury to bone and surrounding soft tissue, the
poorer the outcome. Mild contusions with local bone trauma will heal easily, whereas
severely comminuted injuries with extensive soft tissue damage heal poorly.
Vascular Injury: Inadequate blood supply impairs healing. Especially vulnerable areas are the
femoral head, talus, and scaphoid bones.
Degree of Immobilization: The fracture site must be immobilized for vascular ingrowth and
bone healing to occur. Repeated disruptions of repair tissue, especially to areas with marginal
blood supply or heavy soft tissue damage, will impair healing.
Intraarticular Fractures: These fractures communicate with synovial fluid, which contains
collagenases that retard bone healing. Joint movement will cause the fracture fragments to
more, further impairing union. When intraarticular fractures are comminuted, the fragments
tend to float apart owing to loss of soft tissue support.
Separation of Bone Ends: Normal apposition of fracture fragments is needed for union to
occur. Inadequate reduction, excessive traction, or interposition of soft tissue will prevent
healing.
Infection: Infections cause necrosis and edema, take energy away from the healing process,
and may increase the mobility of the fracture site.
Local Pathology: Any disease process that weakens the musculoskeletal tissue, like
osteoporosis or osteomalacia, may impair union.

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FIBROSIS
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FIBROSIS
The term fibrosis is used more broadly to
denote the excessive deposition of collagen
and other ECM components in a tissue
The terms scar and fibrosis are used
interchangeably
FIBROSIS
Classically activated macrophages
Removal of microbes and dead tissues
Factors: IFN- and TNF
Alternatively activated macrophages
Little microbicidal activities
Greater role in tissue remodelling, angiogenesis
and scar formation
Factors: IL-4 and IL-13
FIBROSIS
Alternatively activated macrophages
produce TGF- and other growth factors that are
involved in the repair process
TGF- is an important fibrogenic agent
Produced by most of the cells in granulation
tissue
Causes fibroblast migration and proliferation,
Increased synthesis of collagen and fibronectin,
and decreased degradation of ECM due to
inhibition of metalloproteinases.
Osteopontin : OPN
Plays an important role in fibrosis of the
heart, lung, liver, kidney
Blockage of OPN expression decreases the
formation of granulation tissue and scarring
FIBROSIS - Osteopontin - OPN
Secretion of non-fibrogenic forms of TGF-
Lack of osteopontin
Absence of a T
H
2 response
Clinically useful antifibrotic agents:
Inhibitors of TGF- binding
Angiogenesis Inhibitors
Toll-like receptors antagonists
IL-13 blockers
FIBROSIS - Scarless healing
Fibrotic disorders
Liver cirrhosis
Systemic sclerosis
Fibrosing diseases of the lung
Idiopathic pulmonary fibrosis
Pneumoconioses
Drug / radiation-induced pulmonay fibrosis
Chronic pancreatitis
Glomerulonephritis
Constrictive pericarditis
Systemic sclerosis
EhlersDanlos
syndrome
Chronic glomerulonephritis
Chronic glomerulonephritis
Figures. (A) Left lateral telecardiogram showing thick intense calcification of
the pericardium consistent with constrictive pericarditis. (B) Increased
respiratory variation of mitral E velocity on pulsed-wave Doppler
echocardiography of left ventricular inflow.
Cirrhosis of
the Liver
E N D
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