Wound Healing

A complex integrated sequence of cellular,

physiologic, and biochemical events initiated by

the stimulus of injury to tissue

Healing process

The same events, in the same order, occur in every

healing process regardless of the tissue type or the

inciting injury
Healing process

The activation of basic cellular processes

of inflammation, cell proliferation, and
growth as well as regulation of these
processes once repair is complete.
Healing process

All repair occurs with an overlapping series of

orchestrated events to limit the damage and restore

the function and integrity of the structure

Types of wound closure

Primary closure
Delayed primary closure
Secondary closure
Closure of partial thickness skin wound
Primary closure

First intention closure

Immediately sealed wounds with simple suturing,
skin graft placement, or flap closure
Eg. emergency laceration repair,
closure of the surgical wound
Primary closure
Secondary closure

No active intent to seal the wound

The wound is closed by reepithelization and

contraction with some deposition of scar tissue
Secondary closure
Delayed primary closure

Tertiary intention
Surgical intervention, such as suturing, skin graft
replacement, or flap design, after repeated
debridement and antibiotics therapy
Delayed primary closure
Partial thickness wound healing
TISSUE RESPONSES TO INJURY

Vascular events

Cellular events

Chemical mediators
Vascular events

Immediate transient vasoconstriction

active vasodilatation

permeability change
TISSUE RESPONSES TO INJURY

Vascular events

Cellular events

Chemical mediators
Cellular events
platelets
neutrophils
macrophages
lymphocytes
fibroblasts
endothelial cells
platelets

Hemostasis

Release of platelet granules

- granules
dense granules
lysosomes
Neutrophils

Protection against infection

Intracellular products release

free radicals
cyclooxygenase products
lipooxygenase products
protease, antiprotease
band2 protein
Macrophages

phagocytosis

initiation of fibroplasia

release cellular products

neutral protease, complement factors,
reactive oxygen metabolites,
growth factors, fibronectin,
interleukin 1, enzyme inhibitors
TISSUE RESPONSES TO INJURY

Vascular events

Cellular events

Chemical mediators
Chemical mediators

Vasoactive agents

Chemotactic factors

Cytokines
Vasoactive agents

Histamin

Serotonin

Arachidonic acid
Cytokines in wound healing

TGF-
PDGF
FGF
EGF
IGF-1
Etc. KGF, CTGF, TNF, interleukins
TGF-

Function ;
stimulates the deposition of collagen and other matrix components
inhibits collagenase activity
blocks plasminogen inhibitor
enhance angiogenesis
chemotactic for fibroblasts, monocytes, and macrophages
PDGF

Function ;
attract the neutrophil, macrophage, and fibroblast to the wound
powerful mitogen of the neutrophil, macrophage, and fibroblast
stimulate fibroblasts to synthesize new extracellula matrix
increase the amount of fibroblast-secreted collagenase
FGF

Function;
stimulate endothelial cells to divide and form
new capillaries
chemoattract endothelial cells and fibroblasts
EGF

Function;
stimulates mitosis in epidermal cells and
fibroblasts
increase the secretion of collagenase by
fibroblasts
WOUND HEALING PHASES

Inflammatory phase

Proliferative phase

Maturational phase
Inflammatory phase

The bodys defenses are aimed at limiting the

amount of damage and preventing further injury

 At the initial time of tissue

disruption, platelets

release coagulation factors

and cytokines to initiate

the healing process

 Within the first day
following tissue injury,
neutrophils attatch to
surrounding vessel walls
and then move through the
vessel walls to migrate to
the wound site
Proliferative phase

angiogenesis

fibroplasia

epithelization
Angiogenesis

The process of new blood vessel formation to

support a healing wound environment

Stimulants ;
tissue hypoxia major stimulus
TNF-, heparin, VEGF, FGF-1, FGF-2
 The fibroplasia phase is
characterized by
movement of wound
macrophages into the site
of injury, which in turn
attract fibroblasts. The
fibroblasts then repair the
site by producing new
connective tissue matrix.
Maturational phase ( = remodeling )

The period of scar contracture with collagen cross-

linking, shrinking, and a loss of edema

 The remodeling phase is
characterized by an
equilibrium between
collagen synthesis and
collagen degradation in an
effort to reestablish the
connective tissue matrix.
MECHANISMS IN WOUND HEALING

Epithelization

Contraction

Connective tissue matrix deposition

Epithelization

1. sealed by clot formation

2. epithelial cell migration across the defect

3. keratinocytes detatchment, migration,

proliferation, differentiation, stratification
MECHANISMS IN WOUND HEALING

Epithelization

Contraction

Connective tissue matrix deposition

Contraction

Inward movement of the edges of the

injured tissue
Begins between days 8 and 10 after
injury
Fibroblast and extracellular matrix
control the process.
MECHANISMS IN WOUND HEALING

Epithelization

Contraction

Connective tissue matrix deposition

Components of extracellular matrix
Collagen
Elastin
Fibronectin
Laminin
Proteoglycans
Hyaluronic acid
Synthesis of collagen

1. Combination of aminoacid to form chains

2. Chains associate to form molecules

3. Molecules associate to form fibrils

4. Fibrils aggregate into fibers or bundles

FACTORS AFFECTING WOUND
HEALING
Types of injury

Age

Medications

Host disease factors

Technical factors
Types of Injury

Sharp injury

Crush injury

Missile injury

Thermal injury
Aging

In vitro decrease in the proliferative potential

of fibroblasts and epithelial cells

Clinically heal more slowly with less scarring

Medications

Steroids & Vitamin A

Anti-inflammatory agents

Phenytoin

Antineoplastic agents

Anticoagulants

Vitamin E
Steroids

Impairing macrophage migration

Altering neutrophil function

Inhibit synthesis of procollagen by

fibroblasts
Vitamin A deficiency

Impair monocyte activation

Inhibit fibronectin deposition

Impairment of TGF- receptors

Vitamin A directly counteracts the effect

of glucocorticoid
Host disease factors

Nutrition Uremia
Infection Malignancy
Wound hypoxia Irradiation
Diabetes Denervation
Jaundice
Nutrition

Protein

Vitamin C decrease in rate and quality of

collagen production

Vitamin K

Minerals zinc, copper

Infection

Bacteria
prolong the inflammatory phase
interfere with epithelization, contraction and
collagen deposition

Endotoxin
collagen degradation and destruction of
surrounding previously normal tissue
Wound hypoxia

Oxygen necessary for normal metabolic cellulat function

Tissue oxygen level 35mmHg

neutrophil bacterial killng, fibroblasts replication
collagen production .
Causes of wound ischemia

Poor arterial flow - atherosclerosis

Poor venous flow venous stasis
Smoking
Radiation
Edema
Diabetes mellitus
Vasculitis
Pressure
Diabetes mellitus

Tissue hypoxia

artherosclerosis, microvascular abnormality

Repetitive trauma
Diabetes mellitus

Susceptable to infection
attenuated inflammatory response
impaired chemotaxis
inefficient bacterial killing
Impaired lymphocyte and leukocyte function
Increased collagen degradation and decreased
deposition
Technical Factors

Surgical technics

Suture materials

Wound care
Surgical technique

Handle gently

Adequate hemostasis

Careful apposition of wound edges

Surgical technique: skin incision

Direction

Length

Location
Suture materials

Absorbable sutures;

Non-absorbable sutures;
Principles of wound management:
open wound
Clean the wound effectively
Achieve moist wound healing
Minimize the periwound edema
Prevent new pressure insult or wound
soilage
Maintain adequate tissue oxygenation
 Agents to optimize wound healing

Dressing

Antibiotics ; controversial

Debriding agents

Phamacologic agents
 Ideal dressing

simple, inexpensive, highly absorptive, nonadherent

achieve moist healing and have antibacterial properties
less frequent dressing change
all-in-one dressing
Wound-healing products(1)

Passive products ; lint

cotton wool

plugging and concealing wounds

Wound-healing products(2)

New dressings ; polymeric films,

polymeric foams,
hydrogels,
hydrocolloids
Classified as interactive dressings, providing a
microenvironment which is conducive to healing
Wound-healing products(3)

Active products which actively stimulate

healing beyond that of the normal

biological maximum.