Principles of Wound Healing
there are many types of wounds, most undergo similar stages
in healing that are mediated by cytokines and other chemotactic
factors within the tissue. The duration of each state varies
with the wound type, management, microbiologic, and other
physiologic factors. There are 4 major stages of wound healing
after a full-thickness skin wound.
Inflammation is the first stage of wound healing.
It can be divided into 2 phases. During the initial phase,
vasoconstriction occurs immediately to control haemorrhage,
followed within minutes by vasodilation. During the second
phase, cells adhere to the vascular endothelium. Within 30
min, leukocytes migrate through the vascular basement membrane
into the newly created wound. Initially, neutrophils predominate
(as in the peripheral blood); later, the neutrophils die off
and monocytes become the predominant cell type in the wound.
Debridement is the second stage of wound healing.
Although neutrophils phagocytose bacteria, monocytes, rather
than neutrophils, are considered essential for wound healing.
After migration out of the blood vessels, monocytes are considered
macrophages, which then phagocytose necrotic debris. Macrophages
also attract mesenchymal cells by an undefined mechanism.
Finally, mononuclear cells coalesce to form multinucleated
giant cells in chronic inflammation. Lymphocytes may also
be present in the wound and contribute to the immunologic
response to foreign debris.
Repair is the third stage of wound healing. It consists
of fibroblast, capillary, and epithelial proliferation phases.
During the repair stage, mesenchymal cells transform into
fibroblasts, which lay fibrin strands to act as a framework
for cellular migration. In a healthy wound, fibroblasts begin
to appear ~3 days after the initial injury. These fibroblasts
initially secrete ground substance and later collagen. The
early collagen secretion results in an initial rapid increase
in wound strength, which continues to increase more slowly
as the collagen fibres reorganize according to the stress
on the wound.
Migrating capillaries deliver a blood supply to the wound.
The centre of the wound is an area of low oxygen tension that
attracts capillaries following the oxygen gradient. Because
of the need for oxygen, fibroblast activity depends on the
rate of capillary development. As capillaries and fibroblasts
proliferate, granulation tissue is produced. Because of the
extensive capillary invasion, granulation tissue is both very
friable and resistant to infection.
Epithelial cell migration begins within hours of the initial
wound. Basal epithelial cells flatten and migrate across the
open wound. The epithelial cells may slide across the defect
in small groups, or “leapfrog” across one another to cover
the defect. Migrating epithelial cells secrete mediators,
such as transforming growth factors a and ß, which enhance
wound closure. Although epithelial cells migrate in random
directions, migration stops when contact is made with other
epithelial cells on all sides (ie, contact inhibition). Epithelial
cells migrate across the open wound and can cover a properly
closed surgical incision within 48 hr. In an open wound, epithelial
cells must have a healthy bed of granulation tissue to cross.
Epithelialization is retarded in a desiccated wound.
Maturation is the final stage of wound healing. During
this period, the newly laid collagen fibres and fibroblasts
reorganize along lines of tension. Fibres in a non-functional
orientation are replaced by functional fibres. This process
allows wound strength to increase slowly over a long period
(up to 2 yr). Most wounds remain 15-20% weaker than the original
Uncomplicated simple lacerations are usually managed by complete
closure if they are not grossly contaminated. The wound should
be thoroughly lavaged and debrided as necessary before closure.
If tension is present on the wound edges, it should be relieved
by tension-relieving suture techniques, sliding tissue flaps,
or grafts. Deep lacerations may be treated according to the
same principles, depending on the extent of the injury. Damage
to underlying structures (eg, muscles, tendons, and blood
vessels) must be resolved before closure. If a laceration
is grossly contaminated with debris, primary closure of the
wound may not be indicated. Contaminated wounds may be closed
with drains or treated as an open wound.
Bite wounds are a major cause of injuries, especially in free-ranging
animals. Cat bites tend to be small, penetrating wounds that
frequently become infected and must be treated as an abscess
with culture, debridement, antibiotics, and drainage. Dog
bites have a more varied presentation. Because of the slashing
nature of dog bite injuries, the major tissue damage is usually
found beneath the surface of the wound. While only small puncture
marks or bruising may be evident on the surface, ribs may
be broken or internal organs seriously damaged. The animal
should be thoroughly examined and stabilized before definitive
wound care is begun. The wound should be surgically extended
as far as necessary to allow a thorough examination and determination
of its extent before a decision on the repair can be made.
After a proper assessment, debridement can be performed. Unless
en bloc debridement is performed, complete wound closure is
usually not recommended because the sites are usually contaminated.
Closure can be accomplished with drains, as a delayed closure,
or by second intention depending on the extent of the injury.
Degloving injuries result in an extensive loss of skin and
a varied amount of deeper tissues. These injuries are a result
of a shear force on the skin. Sources include fan belt injuries
and loss of tissue during a collision with a motor vehicle.
With a physiologic degloving injury, the skin is still present
but completely freed from the underlying fascia. If the injury
results in a loss of blood supply to the skin, necrosis may
develop later. In an anatomic degloving injury, the skin is
torn off the body. Anatomic degloving injuries frequently
require marked and repeated debridement. Differentiating viable
and nonviable tissue may be a problem in the early wound debridement
process. An attempt should be made to salvage tissue in which
viability is questionable. Subsequent debridement can be used
to remove any necrotic tissue. In orthopaedic injuries that
typically accompany degloving injuries, final stabilization
may be delayed until local infection is under control.
gunshot injuries, most of the damage is not visible. As the
projectile penetrates, it drags skin, hair, and dirt through
the wound. If the projectile exits the body, the exit wound
is larger than the entrance wound. The amount of damage caused
by the projectile is a function of its shape, aerodynamic
stability, mass, and velocity. High-velocity projectiles tend
to produce more damage as a result of impact-induced shock
waves that move through the tissue. The shock waves create
blunt force trauma resulting in tissue and vascular damage.
Gunshot wounds are always considered to be contaminated, and
primary closure is generally not recommended. These wounds
should be managed as open wounds or by delayed primary closure.
After initial assessment and stabilization of the animal,
the wound may be explored to evaluate the extent of damage
and to determine a plan for repair. If the projectile caused
a fracture, the method of repair depends on the location and
type of fracture. External fixation or bone plates are common
choices for rigid stabilization of the fracture so that the
soft tissues may be appropriately managed. Gunshot wounds
to the abdomen are an indication for an exploratory celiotomy.
Gunshot wounds to the thorax may require a thoracotomy if
haemorrhage or pneumothorax cannot be conservatively managed.
wounds or decubital ulcers develop as a result of pressure-induced
necrosis. Pressure wounds can be extremely difficult to treat
and are best prevented. Preventive measures include changing
the position of the animal frequently, maintaining adequate
nutrition and cleanliness, and providing a sufficiently padded
bed. Factors that predispose to pressure wounds include paraplegia,
tetraplegia, improper coaptation, and immobility. Mild ulcers
may be managed with debridement and bandaging to prevent further
trauma to the affected site. More severe wounds require extensive
surgical management. After debridement and development of
a granulation bed, an advancement flap or pedicle graft may
be required for closure.
that Interfere with Wound Healing
Factors that interfere with wound healing may be divided by
source into physical, endogenous, and exogenous
categories. Physical factors are environmental issues.
Temperature affects the tensile strength of wounds. Ideal
conditions allow wound healing to occur at 30°C. Decreasing
the temperature to 12°C results in a 20% loss of tensile wound
strength. Adequate oxygen levels are also required for appropriate
wound healing. Because of vessel disruption, wounds contain
lower oxygen levels than surrounding healthy tissue. Low levels
of oxygen interfere with protein synthesis and fibroblast
activity, causing a delay in wound healing. Oxygen levels
may be compromised for many reasons, including hypovolemia,
the presence of devitalised tissue, and excessively tight
factors (previously known as systemic factors) typically
reflect the overall condition of the animal. Anaemia may interfere
with wound healing by creating low tissue oxygen levels. Hypoproteinemia
delays wound healing only when the total serum protein content
is <2.0 g/dL. Because wound healing is a function of protein
synthesis, malnutrition may alter the healing process. The
addition of dl-methionine or cysteine (an important amino
acid in wound repair) prevents delayed wound healing. Uraemia
can interfere with wound healing by slowing granulation tissue
formation and inducing the synthesis of poor quality collagen.
Although diabetes is a known problem with wound healing in
humans, it has not been demonstrated to cause a problem in
animals. Obesity contributes to poor wound healing primarily
as a consequence of poor suture holding in the subcutaneous
Exogenous factors include any external chemical that
alters wound healing. Cortisone is commonly implicated in
wound complications. Corticosteroids markedly inhibit capillary
budding, fibroblast proliferation, and the rate of epithelialization.
Similar to cortisone, vitamin E adversely affects wound healing
by slowing collagen production. This effect may be reversed
with vitamin A. Additional vitamin A will not improve wound
healing in the absence of vitamin E or cortisone. Vitamin
C is required for the hydroxylation of proline and lysine.
Zinc is required for epithelial and fibroblastic proliferation;
however, excessive zinc delays wound healing by inhibiting
macrophage function. Radiation is detrimental to wound healing.
Given 7 days prior to wound creation, healing is impaired.
Administered 7 days following wound creation, it has no effect
on wound strength. Cytotoxic drugs may also delay wound healing.
Alkylating agents (eg, cyclophosphamide, melphalan) slow wound
healing by blocking DNA synthesis.