Chapter 7: Wound Healing

Repair of Skin
Factors That Interfere With Wound Healing Growth
Factors in Wound Repair Surgical Approaches
Wound Dressings
Suture Materials and Needles Tourniquets
 WOUND HEALING

Repair of Skin

There are three basic phases of wound repair: Inflammatory, Fibroblastic and
Maturation

1. Phase 1-Inflammatory Phase Substrate or Lag Phase : This stage lasts 3-4
days and has 3 parts, vascular, hemostatic and cellular.
a. Hemostasis is obtained via active vasoconstriction of blood vessels
damaged in the wound. Aggregation of platelets also leads to the formation
of a hemostatic plug.
b. Platelet adhesion is in part stimulated by exposure of the platelets to
the proline and hyroxyproline matrix of mature collagen and other
connective tissue components exposed by the injury.
c. Once platelets are exposed to and adhere to the connective tissue matrix,
the platelets are activated. This can only occur in the presence of von
Willebrand components of factor VIII which is released from adjacent
endothelial cells. Activation involves the release of ADP from the platelet.
The ADP stimulates other platelets to stick to one anotherplatelet
aggregation.
d. Platelets store calcium and 5-hydroxytryptamine in intracytoplasmic
granules as well as many other growth factors. These are released
upon adhesion and promote further platelet aggregation and
vasoconstriction. This process is termed "degranulation"
e. Platelet stimulation results in activation of phospholipase and hydrolyzed
membrane lipids and the liberation of arachidonic acid. Arachidonic acid is
converted by platelet cyclo-oxygenase into
thromboxane A2. Thromboxane A2 further stimulates platelet aggregation
and is also a potent vasoconstrictor.
f. Contractile protein in the platelet, thrombosthenin, promotes clot
retraction. Clot retraction will not occur unless platelets are present.
g. Coagulation occurs due to the activation of clotting factors.
i. Intrinsic system
ii. Extrinsic system
The end result is the activation of factor X which then converts
prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin
monomers, which polymerize to form a fibrin clot. Fibrin besides promoting
hemostasis, provides a scaffolding for the ingrowth of cells at a later stage.
h. Platelets release a number of other factors at this point which promote
wound healing. These include:
i. Proteolytic enzymes activate the complement system. Also released is 12-
HPETE which in turn stimulates the release of leukotriene B4 an
important chemotaxic agent.
ii. Various platelet derived growth factors which promote various components of
wound healing. (See below)
h. Other substances in the plasma increase vascular permeability. Histamine
is released by mast cells. Histamine increases vascular permeability by causing
contraction of endothelial cells and uncovering
gaps between the cells. Histamine is also a powerful vasodilator. Serotonin
released from the platelet and kinins made from plasma alpha globulins at
the site of injury, also increase vascular permeability.
i. Neutrophils, attracted by the chemotaxic factors arrive in the wound
about 6 hours after the injury. They reach their highest numbers at 1-2 days
post injury. If no infection is present, their numbers decline after this.
Neutrophils are responsible for wound debridement through the release of
collagenolytic and fibrinolytic enzymes. Additionally, neutrophils ingest
bacteria.
j. Lymphocytes reach their maximum number in the wound at day 6.
The most important role of the lymphocyte is the synthesis of lymphokines.
Two of the best known lymphokines are the migration inhibition factor
(MIF) and macrophage activation factor (MAF). MIF attacts macrophages
to the wound and MAF activates them.
k. The macrophages attracted to and activated in the wound are actually
derived from monocytes in the blood. They are the most important
inflammatory cells involved in wound healing for the following reasons:
i. They are the only cells able to tolerate the low oxygen tensions at the
wound edge.
ii. They appear in the wound during the first 5 days and have a long life
span (7-10 days).
iii. Wound healing is severely inhibited in the absence of monocytes.
iv. They process and present antigens to the lymphocytes to initiate immune
response.

NOTE* Activated macrophages have a number of roles.

a. Wound debridement- accomplished by the production and secretion of
proteinases, such as collagensase, etc.
b. Ingestion of bacteria and cell debris
c. Capillary formation-neovascularization is a direct effect of macrophage
stimulation through cytokines
d. Antigen processing and presentation

l. Migratory fibroblasts originate from mesenchymal cells near the wound

edge. These cells become bound to the fibrin laid down in the wound and
proliferate. They then produce glycoproteins. Collagen synthesis begins on
the 5th day post injury and lasts 2-4 weeks.
m. Eosinophil concentration reaches a peak in the injured area between
days 7-14. They may be associated with collagen remodeling and
synthesis occurring at the same time. There are very few and their role is
unclear.
n. Fibronectin is a glycoprotein produced by fibroblasts, endothelial cells and
hepatocytes. Among the functions attributed to fibronectin are:
i. Fibronectin coats macrophages, aiding in opsonization and phagocytosis.
ii. Fibronectin is found on the surface of fibroblasts, where it may aid on the
adhesion of these cells to the extracellular matrix.
iii. Fibronectin cross-links with collagen and glycosaminoglycans. This results
in increased adhesion of epidermal cells and endothelial cells to the dermis.
iv. The matrix formed by fibroblasts and fibronectin creates a framework over
which epidermal cells may migrate.

2. Phase 2- The Proliferative Phase (Migratory/Lag Phase): This stage lasts

from 5-20 days and has three parts: epidermal regeneration, neoangiogenesis,
and collagen synthesis.
a. Epidermal regeneration:
i. The cells at the wound edges flatten out and develop pseudopods
(extensions of their cytoplasm), then migrate across the wound, only
migrating over viable tissue, at a rate directly proportional to the oxygen
tension of the tissues which is highest under hyperbaric conditions. The
aforementioned fibrin-fibronectin network serves as a framework over
which this migration occurs.
ii. Intracellular contractile filaments (actin) develop at the periphery of the
migrating cells. These filaments align themselves with the fibrinectin
strands in the extracellular matrix. The interaction of these strands
actually pulls the epithelial cells along.
iii. Other changes occur- the basement membrane under the epidermal cells
changes; the epidermal cells themselves elongate in the direction of the
wound defect; mitotic activity of the epidermal cells dramatically increases,
and the division and movement of epidermal cells may be under the
direction of epidermal growth factor (EGF).
b. Neoangiogenesis: The formation of new capillary buds from blood vessels
near the wound occurs at the same time as the migration of the epidermis.
The development of capillaries towards the center of the wound may be
under the influence of growth factors released by macrophages. As oxygen
tension increases with the opening of new vascular channels, these growth
factors are inhibited and capillary growth slows and then stops.
c. Collagen Synthesis:
i. Within the injured dermis, fibroblasts (surgeon's cell) begin to appear at the
end of the inflammatory process, and adhere to the dermal collagen and
fibrin. As the capillary structure returns to the wound and oxygen tension
increases, fibroblast replication slows. As oxygen tension further increases,
fibroblasts begin synthesizing collagen.
ii. There are at least 5 types of collagen.
iii. Collagen production by the fibroblasts are under control of at least 5
growth factors.
iv. Collagen at this point represents 50% of the scar.
v. The amount of collagen in the healing wound reaches a maximum at two
to three weeks post injury. Remodeling now begins.
 Tension on the wound stimulates production of collagen which is initially
beneficial.
Therefore excessive tension should be avoided making skin incisions along
the relaxed skin tension lines and using steri-strips when possible.
Note* The wound reaches 35% of its original strength around the 14th day.
The tensile strength of the wound now equals the strength of the suture
and sutures can be removed at this point.

NOTE* A number of factors influence epithelial repair: It has been shown that
cortisone delays formation of granulation tissue and wound closure; causes
thinning of the dermis and atrophy of collagen fibers; and causes a
decrease in fibroblast and new blood vessel proliferation. This effect can be
reduced by vitamin A. Data is conflicting and there are no dosage amounts
or periods of time described as being a minimum for steroids to have their
deleterious effect on wound healing. Therefore, injections of post-op
steroids which is done routinely in podiatry to reduce post-op pain and
edema should be studied more scientifically.

3. Phase 3-The Remodeling Phase (Maturation)- Can last up to a year At

two weeks post injury, a wound has regained only 35% of its tensile
strength. By one month this has increased to 40-50%. A number of
processes occur during the remodeling phase:
a. The entire remodeling process is really an equilibrium between enzymatic
processes lysing and resorbing old collagen and forming new collagen.
b. Wound contraction is part of this remodeing stage of healing.
Contraction progresses at 0.6 to 0.7 mm/day independent of the wound
size, but certain shapes heal faster. Round wounds do not contract as quickly
as rectangular or stellate wounds. Skin grafting diminishes wound
contraction.

Note* Only after 6 months and preferably not before a year do you really
know what a scar will look like, therefore, any attempt at scar revision
should wait at least this long.

Factors That Interfere With Wound Healing

1. Age: Growth rate and multiplication of fibroblasts decrease with age.

2. Inadequate Perfusion: Inadequate perfusion of skin, subcutaneous tissue,

or bone results in a decrease in oxygen delivery to the wound, thereby
impairing healing.

3. Infection: Infection leads to tissue destruction and edema, both of which

interfere with the healing process.

4. Edema: Interferes with tissue perfusion and leads to tissue destruction.

5. Poor Nutrition: Protein depletion results in alterations in collagen

synthesis and cross-linking.
6. Vitamin and Trace Element Deficiencies:
a. Vitamin A deficiency can interfere with wound healing, and may
reverse wound healing problems associated with steroids.

NOTE* Vitamin A taken p.o. to help reverse the effects of steroids can also
reverse the effectiveness of steroids in the condition for which they were
originally intended (kidney transplant; vitamin A can cause rejection).
However, topically vitamin A can be very effective. Have the
pharmacist mix 1000 units of vitamin A per gram of Bacitracin
ointment for steroid patients to apply topically to a wound

b. Vitamin C deficiencies lead to scurvy, a disease associated with the

failure of collagen synthesis.

7. Steroid and Cytotoxic Medications:

a. Steroids slow protein synthesis when given exogenously. Steroids
interfere with capillary budding, slow fibroblast proliferation as well as
the rate of epithelialization.
b. Cytotoxic drugs commonly used in chemotherapy, inhibit cellular
proliferation. In general, wound healing is slowed but not prevented.

8. Radiation: Microvascular changes occurring after tissue is exposed to

radiation at therapeutic doses will lead to perfusion problems if that
tissue is later injured. All cell types involved in healing may be adversely
affected by radiation. Malignant change may also occur.

9. Diseases Which are Associated With or Predispose to Chronic Wounds:

a. Diabetes Mellitus:
i. Deposits in the arteries interfere with tissue perfusion.
ii. Diabetic neuropathy leads to reduced sensation and gait abnormality
iii. Metabolic problems lead to a reduction in nutrients available for
wound healing.
iv. Impaired phagocytosis seen as part of the disease spectrum on
diabetics leads to an increase in bacterial infections and subsequent tissue
destruction.
b. Venous Stasis: Poor venous return leads to an increase in tissue
pressure. The increase in tissue pressure results in underperfusion of the
skin and wounds, as well as accumulation of inhibitory metabolites
c. Collagen Vascular Disease: These diseases have an autoimmune basis and
result in capillary damage leading to poor tissue perfusion and hypoxia,
and immune response to other cells or cell constituents

10. Treatment of Non-healing Wounds:

a. Debridement of necrotic tissue
b. Control of infection
c. Control of diabetes mellitus
d. Nutritional support
e. Avoidance of trauma
f. Aggressive intermittent compression and elevation to eliminate limb
edema
g. Tapering of steroids (paradoxically, topical steroids applied to wound in
patients with collagen vascular disease may control the vasculitis and
actually stimulate wound healing)
h. Revascularization of an ischemic wound through angioplasty or
reconstructive vascular surgery
i. Use of hyperbaric oxygen
j. Plastic reconstructive surgery
k. Application of growth factors (still experimental)

Growth Factors in Wound Repair

With the production of a platelet derived wound healing formula (PDWHF)
known as PROCUREN, a mixture of 5 platelet-produced growth factors,
angiogenesis and other aspects of wound healing are stimulated. The 5
growth factors are
1. Platelet derived growth factor (PDGF)
2. Platelet derived angiogenesis factor (PDAF)
3. Platelet derived epidermal growth factor (PDEGF)
4. Transforming growth factor (TGFB)
5. Platelet factor 4 (PF-4)

Surgical Approaches
Skin incisions are planned according to established principles:
a. Anatomical landmarks including vital structures should be identified and
marked with a skin scribe prior to the initial incision (listen with a doppler for
arterial flow)
b. Tension on the healing incision must be avoided
c. Easy access to all structures involved must be possible
d. The incision should be long enough to avoid excess traction on the
wound margins (remember that skin heals from side-to-side and not from
end-to-end)
e. Vital nerve and blood vessels should be identified and protected, with
skin incisions made parallel to them
f. Incisions should be parallel to relaxed skin tension lines (RSTL) whenever
possible
g. Excessive manipulation and damage to the deeper tissues must be
avoided by following the lines of cleavage (RSTL) and planes of fascia
h. Scars over bony protuberances or weight bearing surface points should
be avoided
i. Longitudinal incisions or incisions perpendicular to the RSTL should be
located in areas of relatively little skin movement
j. Longitudinal incisions that cross flexion or extension surfaces of joints
should be avoided or at least made in a curvilinear fashion to allow for
flexibility and scar contracture
 NOTE* An incision perpendicular to the RSTL will gap widely whereas an
incision made parallel to the RSTL will remain approximated. The RSTL
are created by the directional pull of structures underlying the relaxed
skin. The RSTL are important for the direction they convey. Optimal
healing can be
produced by ensuring that the collagen in the scar forms parallel to the
adjacent dermal collagen. Skin expands and contracts along the of
direction of muscle pull, so that if an incision is made parallel to this
direction, then the body responds by depositing increased amounts of
collagen to strengthen the scar.

To find the RSTL one simply relaxes the skin in the area by passive
manipulation or in areas where there is not much motion the RSTL
can be found by pinching the skin over the area. This will form furrows.
Pinching in line with the RSTL will form a regularly shaped furrow and
pinching oblique to the RSTL will give rise to an S -shaped furrow
Wound Dressings
Optimum wound dressings should remove excess exudate and toxic
components, maintain a high humidity at wound/dressing interface,
allow gasseous exchange, provide thermal insulation, afford protection
from secondary infection, be free from particulate or toxic contaminants
and allow removal without trauma at the dressing change.
1. Categories:
a. Alginates:
i. Sorbsan®
ii. Kaltostat®
b. Hydrogels:
i. Carrington®
ii. Core Care®
iii. MPM®
iv. Intrasite®
v. Sososite®
vi. Biolex®
vii. Vigilon®
c. Foams:
i. Flexan®
ii. Hydrosorb®
iii. Mitraflex®
iv. Polymem®
v. Epilock®
d. Hydrocolloids:
i. Ultec®
ii. Triad®
e. Isotonic Saline:
i. Dermagran®
f. Zinc Saline:
i. Dermagran®
g. Transparent dressings:
i. Tegaderm®
ii. Proclude®
h. Hydrophilic dressings:
i. Dermagran®

Suture Materials and Needles

1. Classification of surgical sutures:
a. Absorbable:
i. Natural filament (from animals):
Plain gut
Chromic gut
ii. Synthetic multifilament:
Dexon-S® (polyglycolic acid)
Vicryl® (polyglactin 910)
iii. Synthetic monofilament:
PDS® (polydioxanone)
Maxon® (polyglyconate)

b. Nonabsorbable:
i. Natural filament
Surgical silk
Dermal silk (Perma-hand)
Surgical linen
ii. Metal
iii. Synthetic monofilament:
Dermalon®, Ethilon® (nylon)
Surgilene® (polypropylene)
Novafil® (polybutester)
iv. Synthetic multifilament
Neurolon®, Surgilon® (nylon)
Mersilene®, Dacron®, Tevdek®, Ethibond®, Ticron®
(polyester)

NOTE* Two principles should be kept in mind when choosing suture and the
caliber of suture. The first one is that the less reactive the suture the less
risk that it may potentiate infection (woven sutures tend to be more
reactive than monofilamentous ones). The second one is that the less
the amount and smaller the caliber of the suture used, the less foreign
material is left inside the wound to potentiate infection. Among the
absorbable stitches the monofilament polyglycolic PDS (looses strength
in 60 days and is absorbed in 180 days) is the least reactive. The
woven polyglycolic, Dexon/Vicryl (looses strength in 30 days and is
absorbed in 70-90 days) is minimally reactive. Among the permanent
stitches, nylon is minimally reactive. Nonabsorbable woven silk, woven
cotton, or absorbable plain/chromic gut should not be used (with specific
exceptions) as they cause acute inflammatory reactions.
2. Biologic properties: All suture materials elicit a foreign body reaction
within the tissues, which lasts for 5-7 days and is relatively the same for all
suture materials. It has been reported that monofilament sutures and
uncoated sutures produce far less reaction than multifilament and coated
sutures. Also synthetic sutures cause less tissue reaction than sutures
derived from natural materials. The best suture appears to be synthetic,
monofilament and nonabsorbable
3. Needle characteristics:
a. Design:
I. Eye
 Closed eye
 French eye
 Swaged (eyeless) (most commonly utilized)
II. Body
 Straight (Keith needle)
 Half curved
 Curved (either 1/4, 3/8, 1/2, or 5/8 circle)
III.Point
 Tapered
Cutting
 Reverse cutting
 Paper cut or diamond point
 Precision-point or hand-honed reverse cutting
Tourniquets
1. Indications: To exert enough pressure on the arterial blood flow to a
limb to produce a bloodless field. Single cuff tourniquets are generally
used for operations lasting less than 90 minutes

2. Contraindications: The final decision whenever to use a tourniquet

rests with the attending physician
a. Open fractures of the leg
b. Post-traumatic hand reconstruction
c. Severe crushing injuries
d. Elbow surgery (with excess swelling)
e. Severe hypertension
f. With skin grafts in which all bleeding points must be readily
distinguished
g. Compromised vascular circulation or in the presence of an arterial graft
h. Diabetes mellitus
i. Sickle cell disease (relative contraindication) as severe postoperative
pain could result

NOTE* Test the hemoglobin and type and level before using a tourniquet on
patients with sickle cell disease or trait

3. Precautions:
a. Carefully exsanguinate the extremity (this prolongs the pain free
tourniquet time)
b. In the presence of malignant tumors, painful fractures, or infection
elastic bandage (Esmarch) exsanguination must not be done, only
elevating the limb for 3-5 minutes is acceptable
c. Do not use an elastic bandage for exsanguination in cases where
bacteria, exotoxin, or malignant cells could spread through the general
circulation
d. Inflation must be done rapidly to occlude arteries and veins
simultaneously
e. Frequent irrigation is recommended when working under tourniquet
control to prevent tissue drying
f. Prolonged tourniquet time can produce permanent or temporary
tissue/nerve/blood vessel damage. It can also produce changes in the
coagulability of blood with an increase in the clotting time
g. If the blood does not return to the limb within 3-4 minutes after release
of the tourniquet, the limb must be placed in a dependent position

4. Adverse Effects:
a. A dull aching pain
b. Stiffness, weariness, reactive hyperemia, skin discoloration
c. Pathophysiological changes due to pressure, hypoxia, hypercarbia, and
acidosis of the tissue can occur after one and one-half hours of tourniquet use.
Symptoms of tourniquet paralysis are:
i. Motor paralysis and loss of touch sensation
ii. Loss of proprioceptive responses
d. Intraoperative bleeding due to:
i. An underpressurized cuff
ii. Insufficient exsanguination
iii. Insufficient cuff pressure
iv. Blood entering through the nutrient vessels of the long bones v.
Inadequate cuff size

5. Pressure Settings: For each patient, the tourniquet should be set to the
minimum effective pressure, taking into account such factors as obesity
preoperative systolic pressure, maximum anticipated rise in the
patient's blood pressure during the surgery, and the presence of
hypertension a. Published literature suggests an effective tourniquet setting
be 75-100 mm Hg above preoperative systolic pressure above the
upper limbs, and two times the preoperative systolic pressure for the
lower limbs when using single bladder cuffs

6. Inflation Time:
a. Depends upon the patient's anatomy, age, and absence of vascular
disease
b. For reasonably healthy adults, there is general agreement that 2 hours
should not be exceeded without releasing the tourniquet for 15-20
minutes before reinflating, and during this time the limb should be
elevated about 60° with steady pressure to the incision

7. Release of Tourniquets:
a. When the tourniquet is released the wound should be protected from
blood surging back by applying pressure dressings and if necessary elevating
the limb
b. If color is not back back within 3 minutes, lower the extremity
c. It has been reported in the literature then upon the release of bilateral
thigh tourniquets (at the same time) a patient developed asystole.
Therefore, this article suggests that when utilizing bilateral thigh tourniquets,
that there be a 5 minute delay between deflation of the cuffs