Far Eastern University Nicanor Reyes Medical Foundation PHASES OF WOUND HEALING

Surgery A Wound Healing

INTRODUCTION
Wound - an injury to living tissue cause by a cut, blow or other
trauma, typically one in which the skin is cut or broken
Wounding disrupts tissue integrity, leading to division of blood
vessels and direct exposure of extracellular matrix to platelets
Wound Healing a complex and dynamic process of replacing
devitalized and missing cellular structures and tissue layers

HISTORY OF WOUND HEALING

2000 B.C., Sumerians employed two modes of treatment:
Spiritual method incantations
Physical method applying poultice-like materials to the
wound
The Egyptians differentiate between infected and diseased
wound compared to non-infected wounds John Hunter (1728-1793): ... the injury alone has in all cases a
1650 B.C., Edwin Smith Surgical Papyrus a copy of a much older tendency to produce the disposition and the means of a cure.
document, describes at least 48 types of wounds Normal wound healing produces a pattern that can be divided
1550 B.C., Ebers Papyrus a document that relates the use of into phases defined by cellular population and biochemical
concoctions containing honey (antibacterial properties), lint activities:
(absorbent properties), and grease (barrier) for treating wounds Hemostasis and Inflammation
The Greeks classified wounds as acute or chronic in nature Proliferation
120-201 A.D., Galen of Pergamum appointed as the doctor to Maturation and Remodeling
the Roman gladiators, emphasized the importance of maintain a Sequence is fluid and overlapping, spanning the time from injury
moist environment to ensure adequate healing. to resolution of acute wounds
Epithelialization rate increases by 50% in a moist wound All wounds must pass through this series of events to successfully
environment as compared to a dry environment re-establish tissue integrity.
1818-1865, Ignaz Philipp Semmelweis a Hungarian obstetrician,
discovered antiseptics in reducing wound infections by noting that Phases of Wound Healing
the incidence of puerperal fever was much lower if students A. HEMOSTASIS AND INFLAMMATION
following cadaver dissection prior to attending childbirth, washed Hemostasis precedes and initiates inflammation with the
their hands with soap and hypochlorite ensuing release of chemotactic factors from the wound site
1822-1895, Louis Pasteur dispelled the theory of spontaneous Exposure of subendothelial collagen to platelets results to:
generation of germs and proving that herms existed in and were Platelet aggregation
always introduced from the environment
Degranulation
1865, Joseph Lister Discovered the use of phenol through the
Activation of coagulation cascade
sewer systems of Glasgow, Scotland, began soaking his surgical
Platelet α granules release wound active substances:
instruments in phenol and spraying the operating rooms, reducing
Platelet-derived growth factor (PDGF)
post-op mortality rates from 50% to 15%
Transforming growth factor-β TGF-β
1876, Robert Wood Johnson Began 10 years of research that
Platelet-activating factor (PAF)
resulted in the production of an antiseptic dressing in the form of
Fibronectin
cotton gauze impregnated with iodoform
Serotonin
1960s-1970s led to the development of polymeric dressings that
Fibrin clot serves as scaffolding for the migration of
can be custom made to specific parameters (permeability to gas,
inflammatory cells (poly-morphonuclear [PMNs] leukocytes
varying degrees of absorbency and different physical forms)
and monocytes) into the wound
Currently, the practice of wound healing encompasses
Cellular infiltration sequence:
manipulation of inflammatory cytokines, growth factors and
1. PMNs enter the wound site (peaking at 24-48hrs)
bioengineered tissues. Combination of all these modalities that
2. Increased vascular permeability
enables optimal wound healing
3. Local prostaglandin release
4. Presence of chemotactic substances (complement
factors, IL-1, TNF-α, TGF-β, Platelet Factor , bacterial
products) stimulate neutrophil migration

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 Neutrophils primary role is phagocytosis of bacteria and T-Lymphocytes less numerous than macrophages, third to
tissue debris invade the wound
Neutrophil factors implicated in delaying the Peaks 1 week post-injury
epithelial closure of wounds Bridge the transmission from the inflammatory to the
Functions of PMNs: proliferative phase of healing
First population of inflammatory cells that invades the Active role in modulation of the wound environment
wound Decrease of T-lymphocytes decreases wound strength
Major source of cytokines during early inflammation, and collagen content
3 +
especially TNF-α , which has a significant influence on Selective depletion of CD8 suppressor (a subset of T-
angiogenesis and collagen synthesis lymphocytes) enhances wound healing
+
Release proteases such as as collagenases, which Depletion of CD4 suppressor has no effect
participates in matrix and ground substances Exert a down-regulating effect on fibroblast collagen
degradation, they do not participate in collagen synthesis by:
deposition Cell associated interferon (IFN)-γ
Macrophages: TNF-α
Second population of inflammatory cells that invades IL-1
the wound Effect is lost if cells are physically separated
Essential to successful wound healing and has a
significant role in angiogenesis, matrix deposition and
remodeling
Derived from circulating monocytes
Peaks 48 to 96hrs post injury and remain present until
wound healing is complete
Participates, along with neutrophils, in wound
debridement via phagocytosis and contribute to
microbial stasis via oxygen radicals and nitric oxide
synthesis
Most pivotal function is the activation and recruitment
of other cells via:
Mediators (cytokines, growth factors)
Cell to cell interaction
Intercellular adhesion molecules (ICAM)
Regulate cell proliferation, matrix synthesis and
angiogenesis by releasing:
TGF-β
Vascular Endothelial Growth Factor (VEGF)
Insulin-like Growth Factor (IGF)
Epithelial Growth Factor (EGF)
Lactate

B. PROLIFERATION
Second phase of wound healing and spans from the 4th to 12th
day
Tissue continuity is re-established
Fibroblasts and endothelial cells last cell population to
invade the wound
PDGF strongest chemotactic factor for fibroblasts (mediated
by cytokines and growth factors) to carry out their function of
matrix synthesis and remodeling
Wound fibroblasts synthesize more collagen than non-
wound fibroblast, by proliferating less and actively
carrying out matrix contraction

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 Lactate a potent regulator of collagen synthesis through a
mechanism involving adenosine diphosphate (ADP)-
ribosylation
Endothelial cells participate in angiogenesis
Migrate from intact venules to close wound
Migration, replication and new capillary tubule
formation is via:
TNF-α
TGF-β
VEGF
Matrix Synthesis
1. Collagen most abundant protein in the body
Critical role in successful wound healing
Deposition, maturation and remodeling are essential for the
functional integrity of the wound
Type I and III involved in wound healing
Type I major component of the ECM of the skin
Type III present in skin, more prominent and important in
repair process
Collagen synthesis dependent on systemic factors such as
adequate oxygen supply, presence of sufficient nutrients and
cofactors and local wound environment
2. Proteoglycans GAGs comprise a large portion of the ground
substance that makes up the granulation tissue, they couple with
proteins to form proteoglycans
Major GAGs found in wounds: dermatan and chondroitin
sulphate (peak during first 3 weeks of healing)
As scar collage in deposited, proteoglycans are incorporated
into collagen scaffolding
C. MATURATION AND REMODELING
Begins during the fibroblastic phase
Characterized by a reorganization of previously synthesized
collagen
Matrix metalloproteinase (MMP) breaks down collagen
Net wound collagen balance between collagenolysis and
collagen synthesis
Pattern for the deposition of matrix in the wound:
Early matrix scaffolding fibronectin and collagen type
III
Middle matrix scaffolding GAGs and proteoglycans
Final matrix collagen type I
After weeks of injury, collagen amount in the wounds reaches
a plateau but tensile strength increases
Fibril formation and cross-linking results from:
Decrease collagen solubility
Increased strength
Increased resistant to enzymatic degradation
Fibrillin a glycoprotein secreted by fibroblast, essential for
the formation of elastic fibers in connective tissue
Scar remodeling continues for 6-12 months post injury
resulting in a mature, avascular and acellular scar
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Mechanical strength of the scar never achieves that of
uninjured tissue
Epithelialization
Restoration of external barrier
Characterized primarily by proliferation and migration of epithelial
cells adjacent to the wound
Process begins within 1 day of injury, seen as a thickening of the
epidermis at the wound edge
Marginal basal cells lose their firm attachment to the
underlying dermis and begins to enlarge and migrate across the
surface of the provisional matrix
Fixed basal cells a zone near that cut edge, undergoes a series
of rapid mitotic divisions, and move in a leap-frog fashion until the
defect is covered
Migrating epithelial cells lose their flattened appearance and
become columnar and increase their mitotic activity once the
defect is bridge
Re-epithelialisation is complete in less than 48 hours, but may
take longer in the case of larger wounds with epidermal/dermal
defect
Promoters of epithelialisation:
EGF
TGF-β
Basic fibroblast growth factor (bFGF)
PDGF
IGF-1
Role of Growth Factors in Normal Healing
Growth factors and cytokines are polypeptides produced in
normal and wounded tissue that stimulate migration,
proliferation and function
Most growth factors are extremely potent and produce significant
effects in nanomolar concentrations
Acts in an autocrine, paracrine and endocrine manner
Growth factors participating in wound healing:

Wound Contraction
All wounds undergo some degree of contraction
Myofibroblast major cell responsible for contraction, differs
from normal fibroblast by possessing a cytoskeletal structure
Stress fibers α-smooth muscle actin in thick bundles, gives the
myofibroblasts contractile capability
HERITABLE DISEASSES OF CONNECTIVE TISSUE
a group of generalized, genetically determined, primary disorders
of one of the elements of the connective tissue: collagen, elastin
or mucopolysaccharide
A. Ehler-Danlos Syndrome
a group of 10 disorders that present as a defect in collagen
formation
Half of the patients manifest defects encoding the alpha
chains of collagen type V, causing it to be either quantitatively
or structurally defected
Phenotypic findings: thin, friable skin with prominent veins,
easy bruising poor wound healing, atrophic scar formation,
recurrent hernias and hyperextensive joints
Gastrointestinal problems: bleeding, hiatal hernia, intestinal
diverticulae and rectal prolapsed
Small vessels are fragile, making it hard for suturing
Large vessels may develop aneurysms, varicosities or
arteriovenous fistulas or spontaneously ruptures
Has 10 types and a recently recognized form characterized by
tenascin-X deficiency
Dermal wounds should be closed in two layers
External fixation with adhesive tape can help reinforce the
scar and prevent stretching
B. Marfan’s Syndrome
Have tall stature, arachnodactyly, lax ligaments, myopia,
scoliosis, pectus excavatum, and aneurysm of the ascending
aorta and are prone to hernias
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Defect in FBN1 gene which codes for fibrillin
Surgical repair of a dissecting aneurysm is difficult, as the soft
connective tissue fails to hold the sutures
Skin may be hyperextensible but shows no delay in wound
healing
C. Osteogenesis Imperfecta
Have brittle bones, osteopenia, low muscle mass, hernia and
ligament and joint laxity
Mutation in type I collagen
Patients experience dermal thinning and increased
bruisability
Surgery can be successful but difficult due to their brittle
bones
D. Epidermolysis Bullosa
Subtypes: EB simplex, Junctional EB, dystrophic EB and
Kindler’s syndrome
First three determined by location in the skin layer, last
present as multiple blisters in different skin layers
Manifestations include impairment in tissue adhesion with the
epidermis, basement membrane or dermis resulting in tissue
separation and blistering
Defect in COL7A1 gene, encodes for Type VII collagen
Management is a challenge due to nutritional status, oral
erosions and esophageal obstruction
Non adhesive pads covered by a bulky dressing to avoid
blistering
E. Acrodermatitis Enteropathica
Inability to absorb sufficient zing from breast milk or food
Defect on chromosome 8q24.3, SLC39A4 gene
Impaired in wound healing as well as erythematous pustular
dermatitis involving the extremities and areas around the
bodily orifices
HEALING IN SPECIFIC TISSUES
A. Gastrointestinal Tract
Healing of full-thickness begins with a surgical or mechanical
reposition of the bowel ends
Sutures or staples are principally used
Failure in healing results in dehiscence, leaks and fistulas
Excessive healing can cause stricture formation and stenosis of
the lumen
The submucosal layer of the GIT imparts the greatest tensile
strength and greatest suture holding capacity
Serosal healing is essential for quickly achieving a watertight
seal from the luminal side of the bowel
Esophagus and Rectum segments of the bowel that are
extraperitoneal and lacks serosa, has a significant higher rates
of anastomotic failure
Mesothelial (serosal) and mucosal healing can occur without
scarring
 There is a significant decrease in marginal strength during the
first week due to an early collagenolysis
Pseudomonas aeruginosa undergo phenotypic shifts
characterized by higher collagenase secretion in an
injured/anastomosed bowel environment
First 3-5 days, collagen breakdown far exceeds synthesis
Collagenase is expressed post-injury in all segments, but more
marked in the colon compared to the small bowel
Technical Considerations
In order for anastomosis to heal without complications, it must
be:
Tension free
Adequate blood supply
Adequate nutrition
Free of sepsis
Stapled ileo-colic anastomoses have fewer leak rates than hand-
constructed ones
Amount of IV fluid administered peri-operatively affects many
aspects of recovery from colonic surgery
B. Bone
Initial stage of hematoma formation consists of accumulation
of blood at the fracture site, containing devitalized soft tissue,
dead bone and necrotic marrow
Next stage accomplishes the liquefaction and degradation of
nonviable products at the fracture site
Normal bone adjacent to the injury undergo revascularization
3-4 days post injury, soft tissue forms a bridge between the
fracture bone segments, forming soft calluses.
The soft tissue serve as internal splint, preventing damage to
the newly laid blood vessels and achieving a fibrocartilaginous
union
Soft callus is formed externally along the bone shaft and
internally along the marrow cavity, this phase characterized by
the end of pain and inflammatory signs
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Hard callus stage mineralization of the soft callus and the
conversion to bone, taking up to 2-3 months
Remodeling stage excessive callus is reabsorbed and the
marrow cavity is recanalized, restoring the contours of the
bone
Growth factors and cytokines for bone healing:
Bone morphogenic proteins (BMPs) from the TGF-β
family
PDGF
TNF-α
bFGF
C. Cartilage
Injuries to the cartilage may be associated with permanent
defects due to meagre and tenuous blood supply
Healing response depends on depth of the injury
Superficial injury disruption of the proteoglycan matrix and
injury to the chondrocytes, no inflammatory response. There
is increase of synthesis of the proteoglycan and collagen,
dependent on the chondrocytes. Slow to heal and result in
persistent structural defect
Deep injuries involve underlying bone and soft tissue,
leading to exposure of vascular channels of the surround
damaged tissues that helps in the formation of granulation
tissue. Hemorrhage initiates inflammatory response and
mediates cellular function for repair. Hyaline cartilage is
formed restoring the structural integrity of the injured site
D. Tendon
Laceration, rupture and contusion
Similar fashion in other areas of the body
Restoration of mechanical integrity may never equal to that of
an undamaged tendon
Hypovascular tendon heal with less motion and more scar
formation than tendon with better blood supply
Tenocytes metabolically active and retain a large
regenerative potential even in the absence of vascularity
E. Nerve
Three types of nerve injuries:
Neurapraxia focal demyelination
Axonotmesis interruption of axonal continuity but
preservation of Schwann cell basal lamina
Neurotmesis complete transaction
Pattern of changes in nerve injury:
Survival of axonal cell bodies
Regeneration of axons that grow across and the
transected nerve to reach the distal stump
Migration and connection of the regenerating nerve
ends to the appropriate nerve ends or organ targets
Wallerian degeneration phagocytes remove the
degenerating axons and myelin sheath from the distal stump
Regenerating axonal sprouts from the proximal to the distal
stump
 Growth factors of nerve healing:
Nerve growth factor
Brain-derived neurotrophic factor
Basic and acidic fibroblastic growth factors
Neuroleukin
Cell adhesion molecules:
Neuron-glia adhesion molecule
Myelin adhesion glycoprotein
Nerve adhesion molecules
N-cadherin

F. Fetal Wound healing

Lack of scar formation and resembles tissue regeneration
Transition wound occurs at the the beginning of the third
trimester, there is scarless healing, but there is loss of the
ability to regenerate skin appendages
Mechanical integrity and strength - normal process is
Wound Environment characterized by a constant and continual increase that reaches
Fetus is bathed in a sterile, temperature-stable fluid environment plateau at some point post-injury
Wounds with delayed healing has decreased wound-breaking
Inflammation strength, but eventually achieve same integrity as normal healing
Extent and robustness of inflammatory response correlates wound
directly with the amount of scar formation in all healing wounds Conditions that cause delayed healing:
Reduced fetal inflammation due to the immaturity of the fetal Nutritional deficiencies
immune system may partially explain the lack of scarring observed Infections
Fetus contains lower numbers of PMNs and macrophages Severe trauma
Impaired healing failure to achieve mechanical strength
Growth Factors equivalent to normally healed wounds. Seen in patients with:
Notable absence of TGF-β Diabetes
Chronic steroid usage
Wound Matrix Tissues damaged by radiotherapy
Excessive and extended hyaluronic acid production Systemic and local factors that affect wound healing:
Components of amniotic fluid, specifically, fetal urine have a
unique ability to stimulate hyaluronic acid production
Fetal fibroblasts produce more collagen

CLASSIFICATIONS OF WOUNDS
ACUTE WOUNDS
Heal in a predictable manner and time frame
Surgical wounds heal in several ways:
a) Primary intention incised wound that is clean and closed
by sutures.
b) Secondary intention wound is left open by granulation
tissue formation and contraction, because of bacterial
contamination or tissue loss
c) Tertiary intention delayed primary closure, combination
of the first two: placement of sutures, allowing the wound Factors Affecting Wound Healing
to stay open for a few days, and the subsequent closure of 1. Advanced Age
sutures Produces intrinsic physiological changes that result in delayed
or impaired wound healing
Increased incidence of cardiovascular disease, metabolic
diseases and cancer, and widespread use of drugs impairs
wound healing of the elderly

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 A significant delay of 1.9 days in epithelialization for patients
>70 years old compared to young adults
Younger individuals have a higher amount of total α-amino
nitrogen in their wounds, a reflection of total protein content
of wound
Noncollagenous protein accumulation at wounded sites is
decreased with aging, impairing mechanical properties of
scarring
2. Hypoxia, Anemia and Hypoperfusion
Low oxygen tension has a profoundly deleterious effects on all
aspects of wound healing
Fibroplasia is impaired by local hypoxia
Optimal collagen synthesis requires oxygen as a cofactor,
specifically for the hydroxylation steps
Major factors affecting local oxygen delivery include
hypoperfusion either systemic or local causes
Level of vasoconstriction of subcutaneous capillary bed is
responsive to:
Fluid status
Temperature
Hyperactive sympathetic tone induced by post-
operative tone
Mild to moderate normovolemic anemia does not appear
to adversely affect wound oxygen tension and collagen
synthesis unless hematocrit falls between 15%
3. Steroids and Chemotherapeutic Drugs
Chronic use of glucocorticoids reduce collagen synthesis and
wound strength
Steroids inhibit the inflammatory phase of wound healing
and release of lysosomal enzyme, epithelialization,
contraction and contribute to increase rates of wound
infection
The stronger the anti-inflammatory effect of the steroid
compound used, the greater the inhibitory effect on wound
healing
Use should be delayed post-operatively to reduce effect on
wound healing
Vitamin A antagonizes the effect of steroid drugs
Chemotherapeutic antimetabolite drugs inhibit early cell
proliferation and wound DNA and protein synthesis
Extravasation of most chemotherapeutic agents is associated
with:
Tissue necrosis
Marked ulceration
Protracted healing at the affected site
4. Metabolic Disorders
a) Diabetes mellitus best known metabolic disorder that
affects wound healing by:
increased rates of wound infection and failure
reduce inflammation, angiogenesis and collagen synthesis
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defects in granulocyte function, capillary growth and
fibroblast proliferation
Obesity, insulin resistance, hyperglycemia and diabetic
renal failure contribute to impaired wound healing in
diabetics
Type 1 diabetics decrease wound collagen accumulation,
independent of degree of glycemic control
Type 2 diabetics no effect on collagen accretion
Diabetic wounds lack sufficient growth factors levels
Correction of blood sugar levels, pro-operation, improves
outcome of wound healing
b) Uremia
Decreased wound collagen synthesis and breaking strength
Use of dialysis to correct metabolic abnormalities and
nutritional restoration should impact greatly on the wound
outcome of patients
c) Obesity
Uncomplicated obesity the absence of co-morbid
conditions such as cardiovascular diseases, diabetes or
respiratory insufficiency, has deleterious effects on wound
healing
Visceral adiposity leads to development of metabolic
syndrome
Pre-adipocytes infiltrate the dermis, their regulatory
mechanisms are different from dermal or wound fibroblasts
Obese patients have higher risk for wound dehiscence,
surgical site infections, incisional hernias, seromas,
hematoma and fat necrosis
Increased subcutaneous fats has a 10-fold increased risk for
anastomotic leaks, abdominal collection and wound
infections
5. Nutrition
Poor nutritional intake or lack of individual nutrients
significantly alters many aspects of wound healing
Induction of energy-deficient states that by providing only
50% of normal caloric requirement leads to:
Decreased granulation tissue formation
Matrix protein deposition
Malnutrition correlates clinically with enhanced rate of wound
complications and increased wound failure post-operation,
reflecting:
Impaired healing response
Reduced cell mediated immunity
Reduced phagocytosis
Reduced intracellular killing of bacteria by
macrophages and neutrophils
The degree of nutritional impairment need not be long-
standing in humans, patients with brief preoperative illness or
reduced nutrient intake will demonstrate impaired fibroplasia
after injury
 Brief and not necessarily intensive nutritional intervention can Antimicrobial Prophylaxis for Surgery
reverse of prevent decreased collagen deposition
Arginine most active in terms of enhancing wound
fibroplasias.
In healthy individuals, arginine supplementation
enhanced collagen and protein deposition at the wound
site
Vitamin C
Deficiency (Scurvy) leads to failure in collagen synthesis
and cross linking,
Increase in severe wound infection.
Recommended dietary allowance: 60mg daily
Vitamin A
Increases inflammatory response and increase the
lability of lysosomal membranes.
Increase collagen production and epidermal growth
factor receptors.
Restores wound healing properties impaired by
diabetes, tumor formation, cyclophosphamide and
radiation
Recommended dose for severely injured patients:
25,000 to 100,000 IU per day
Trace elements
Cofactor or part of an enzyme that is essential for
homeostasis and wound healing
Zinc
Deficiency leads to
Decreased fibroblast proliferation
Decreased collagen synthesis
Impaired overall wound strength
Delayed epithelialization
Defects are reversible by zinc supplementation

The mere presence of bacteria does not constitute an infection

6. Infection
and is often confused with contamination and colonization:
Occurrence is of major concern when implants are used and
Contamination presence of bacteria without
may lead to removal of prosthetic materials, subjecting the
multiplication
patient to further risk
Colonization multiplication without host response
Weaken abdominal closure resulting to wound dehiscence or
Infection presence of host response in reaction to
recurrence of hernia
deposition and multiplication of bacteria
Lead to disfiguring, unsightly or delayed closures
Hyperglycemia a significant risk factor of post-operative
Surgery breaches the intact epithelium allowing bacterial
infections
access to deep tissues and the bloodstream
Moderate control: 120-180mg/dL
Antibiotic prophylaxis is most effective when adequate
The state of the subcutaneous capillary bed can cause infection
concentrations are present in the tissues at the time of
secondary to impaired oxygen delivery. Factors that can cause
incision
this:
Classification of wound infections:
Hypovolemia
Superficial incisional most common
Hypothermia
Deep incisional adjacent to the fascia, above or below,
Stress
most dangerous type is necrotizing fasciitis
Organ / Space wound infection involves fascia,
muscle or abdominal cavity

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CHRONIC WOUNDS Diabetic Wounds
Wounds that have failed to produced satisfactory anatomic and Contributed by neuropathy, foot deformity and ischemia
functional integrity Once ulceration occurs, chances of healing are poor
Majority of wounds that have not healed in 3 months are Treatment should address the possible presence of Osteomyelitis
considered chronic and employ antibiotics that achieve adequate levels both in soft
Skin ulcers considered chronic in nature tissue and bone
Factors causing chronic wounds:
Repeated trauma
Poor perfusion or oxygenation
Excessive inflammation
Unresponsiveness to normal regulatory signals
Failure of normal growth factor synthesis
Over expressed protease activity or failure of anti-
protease mechanism

Ischemial Arterial Ulcers

Occur due to a lack of blood supply
Painful at presentation
Associated with peripheral vascular disease:
Intermittent cluadication
Rest pain
Night pain
Color or trophic changes
Decubitus or Pressure Ulcers
Present at the most distal potion of the extremities, proximal
Localized are of tissue necrosis that develops when soft tissue is
lesions are also encountered
compressed between a bony prominence and an external surface
Diminished or absent pulses with decreased ankle-brachial index
Formation is increased by the presence of friction, shear forces
and poor formation of granulation tissue
and moisture
Signs of peripheral ischemia:
Stages of pressure ulcer formation:
Dryness of skin
STAGE MORPHOLOGICAL CHANGES
Hair loss
I Non-blanching erythema of
Scaling
intact skin
Pallor II Partial-thikness of skin loss
The wound is shallow with smooth margins with a pale base involving epidermis or dermis or
Revascularization or re-establish blood adequate blood supply both
progress to healing III Full thickness skin loss, not
thorugh the fascia
Venous Stasis Ulcers IV Full thickness loss with extensive
involvement of muscle and bone
Due to venous stasis and hydrostatic back pressure
Treatment comprises debridement of all necrotic tissue,
Alteration and distension of the dermal capillaries with leakafe of
maintenance of a favourable moist wound environment that will
fibrinogen into the tissues
facilitate:
Venous hypotension and capillary damage lead to extravasation
Healing
of haemoglobin
Relief of pressure
Lipodermatosclerosis due to the brownish pigmentation of skin
Addressing host issues: nutritional, metabolic and
combined with subcutaneous fat
circulatory status
The wound is usually shallow with irregular margins and
pigmented surrounding skin
EXCESS HEALING
Treatment is compression therapy, via rigid or flexible means
Clinical manifestations:
Most common is rigid: zinc oxide-impregnated, non-
Skin mutilating or debilitating scars, burn contractions
elastic bandage
Tendons frozen repairs
Most ulcers are healed with perseverance and addressing the
GI Tract strictures or stenosis
venous hypertension
Solid Organs cirrhosis, pulmonary fibrosis
Peritoneal cavity adhesive diseases

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Hypertrophic Scars and Keloids
Represent an over abundance of fibroplasias in the dermal healing
process
Hypertrophic scars
Develop 4 weeks within trauma
Stays within boundaries of the wound
Formation is independent of site, age and race
Occur across areas of tension and flexor surfaces
Initially erythematous and raised and over time evolve into
pale, flatter scars
Rise above the skin level and regress over time
Keloids
Results from surgery, burns, skin inflammation, acne,
chickenpox, zoster, folliculitis, lacerations, abrasions,
tattoos, vaccinations, injections, insect bites, ear piercings
or may arise spontaneously
Occur 3 months to years after initial insult, minor injuries
can cause large lesions
Pedunculated lesions with a soft to rubbery or hard
consistency
Rise above the skin, extend beyond the border or original
wound, rarely regress
Peritoneal Scarring
Fibrous bands of tissues formed between organs that are
normally separated and or with the internal body wall
Results from peritoneal injury, prior to surgery or due to intra-
abdominal infection
Major strategies for adhesion prevention or reduction:
Trauma is minimized within the peritoneum by careful
tissue handling, avoiding desiccation and ischemia, and
spare use of cautery, laser and retractors
Introduction of barrier membranes and gels which separate
and create barriers between damaged mesothelial surfaces,
allowing for adhesion-free healing
TREATMENTS OF WOUNDS
Local Care
Begins by obtaining proper and careful history prior to injury
Followed by examination of the wound to asses depth and
configuration of the wound
Antibiotics and tetanus prophylaxis may be needed
Followed by anesthetizing the wound if possible
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Lidocaine or bupivacaine combined with diluted
epinephrine proves satisfactory anaesthesia and hemostasis
Epinephrine should not be used in wounds of the fingers,
toes, ears, nose or penis due to risk of tissue necrosis
secondary to terminal arteriole vasospasm
Irrigation to visualize all areas of the wound and remove foreign
material is best accomplished with normal saline
High-pressure wound irrigation is more effective in achieving
complete debridement of foreign material and nonviable tissues.
Iodine, povidone-iodine, hydrogen peroxide, and organically
based antibacterial preparations have all been shown to impair
wound healing due to injury to wound neutrophils and
macrophages, and thus should not be used.
All hematomas present within wounds should be carefully
evacuated and any remaining bleeding sources controlled with
ligature or cautery.
If the injury has resulted in the formation of a marginally viable
flap of skin or tissue, this should be resected or revascularized
prior to further wound repair and closure.
The area surrounding the wound should be cleaned, inspected,
and the surrounding hair clipped.
Plastic surgical techniques such as W- or Z-plasty are seldom
recommended for acute wounds
Great care must be taken to realign wound edges properly,
important for wounds that cross the vermilion border, eyebrow,
or hairline.
In general, the smallest suture required to hold the various layers
of the wound in approximation should be selected in order to
minimize suture-related inflammation.
Nonabsorbable or slowly absorbing monofilament sutures are
most suitable for approximating deep fascial layers, particularly in
the abdominal wall.
Subcutaneous tissues should be closed with braided absorbable
sutures, with care to avoid placement of sutures in fat.
In areas of significant tissue loss, rotation of adjacent
musculocutaneous flaps may be required to provide sufficient
tissue mass for closure.
In areas with superficial tissue loss, split-thickness skin grafting
may be required and will speed formation of an intact epithelial
barrier to fluid loss and infection.
After closing deep tissues and replacing significant tissue deficits,
skin edges should be reapproximated for cosmesis and to aid in
rapid wound healing.
Failure to remove the sutures or staples prior to 7 to 10 days after
repair will result in a cosmetically inferior wound.
The developments of octyl-cyanoacrylate tissue glues have shown
new promise for the management of simple, linear wounds with
viable skin edges.
Antibiotics
Should only be used when there is obvious infection
Based on organisms suspected to be found within the infected
wound and the patient’s overall immune status
Dressings
Provide ideal environment for wound healing
Mimics the barrier role of epithelium and prevents further damage
Compression provides hemostasis and limits edema
Controls the level of hydration and oxygen tension within the
wound
Occlusion is contraindicated in infected and/or highly exudated
wound
Primary dressing placed directly on the wound and may provide
absorption of fluids and prevent desiccation, infection and
adhesion of a secondary dressing
Secondary dressing placed on top of the primary dressing fur
further protection, absorption, compression and occlusion
Type of Dressings:
Absorbent Dressings
Should absorb without getting soaked through to avoid bacteria
from the outside entering the wound
Nonadherent Dressings
Impregnated with paraffin, petroleum jelly, or water-soluble jelly
Occlusive and Semi-occlusive Dressings
Provide a good environment for clean, minimally exudative
wounds.
Water-proof and impervious to microbes but permeable to water
vapour and oxygen
Hydrophilic and Hydrophobic Dressings
Components of a composite dressing
Hydrophilic dressing aids in absorption
Hydrophobic dressing is waterproof and prevents absorption
Hydrocolloid and Hydrogel Dressings
Hydrocolloid and hydrogel dressings attempt to combine the
benefits of occlusion and absorbency
Useful for burn treatment
Alginates
Derived from brown algae and contain long chains of
polysaccharides containing mannuronic and glucuronic acid
Used when there is skin loss, in open surgical wounds with
medium exudation, and on full-thickness chronic wounds.
Absorbable Materials
Used within wounds as haemostats and include collagen, gelatin,
oxidized cellulose, and oxidized regenerated cellulose.
Medicated Dressings
Used as a drug-delivery system to increase epithelialization.
Agents delivered in the dressings include benzoyl peroxide, zinc
oxide, neomycin, and bacitracin-zinc.
The type of dressing to be used depends on the amount of wound
drainage.
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Nondraining wound drainage <1 to 2 mL/d may require a
semiocclusive or absorbent nonadherent dressing.
Moderately draining wounds (3 5 mL/d) can be dressed
with a nonadherent primary layer plus an absorbent
secondary layer plus an occlusive dressing to protect
normal tissue.
Heavily draining wounds (>5 mL/d) require a similar
dressing as moderately draining wounds, but with the
addition of a highly absorbent secondary layer.
Mechanical Devices
Augments and improves on certain functions of dressings, in
particular the absorption of exudates and control of odor.
This form of therapy has been found to be effective for chronic
open wounds (diabetic ulcers and stages III and IV pressure
ulcers), acute and traumatic wounds, flaps and grafts, and
subacute wounds.
Skin Replacements
All wounds require coverage in order to prevent evaporative
losses and infection and to provide an environment that promotes
healing.
Both acute and chronic wounds may demand use of skin
replacement, and several options are available:
Conventional Skin Grafts
Skin grafts have been used to treat both acute and chronic
wounds.
Split/partial thickness grafts consist of the epidermis plus part
of the dermis, require less blood supply to restore skin function
Full-thickness grafts retain the entire epidermis and dermis.
The dermal component lends mechanical strength and resist
wound contraction, resulting in improved cosmesis
Autologous grafts (autografts) are transplants from one site on
the body to another
Allogeneic grafts (allografts, homografts) are transplants from a
living nonidentical donor or cadaver to the host, require available
tissue and are subjected to rejection and may contain pathogens
Xenogeneic grafts (heterografts) taken from another species
and also require available tissue and are subjected to rejection
and may contain pathogens
The use of skin grafts or bioengineered skin substitutes and other
innovative treatments cannot be effective unless the wound bed
is adequately prepared.
Temporary placement of allografts or xenografts may be used to
prepare the wound bed.
Skin Substitutes
Originally devised to provide coverage of extensive wounds with
limited availability of autografts
Have gained acceptance as natural dressings.
Combine novel materials with living cells to provide functional
skin substitutes, providing a bridge between dressings and skin
grafts.
 Cultured epithelial autografts (CEAs) represent expanded
autologous or homologous keratinocytes.
Expanded from a biopsy of the patient’s own skin, will not
be rejected, and can stimulate re-epithelialization as well
as the growth of underlying connective tissue.
Keratinocytes harvested from a biopsy roughly the size of
a postage stamp are cultured with fibroblasts and growth
factors and grown into sheets that can cover large areas
and give the appearance of normal skin.
CEAs are available from cadavers, unrelated adult donors,
or neonatal foreskins.
Viable fibroblasts can be grown on bioabsorbable or
nonbioabsorbable meshes to yield living dermal tissue that can
act as a scaffold for epidermal growth.
This approach has the virtue of being less time-consuming
and expensive than culturing keratinocyte sheets.
There are a number of commercially available,
bioengineered dermal replacements approved for use in
burn wound treatment as well as other indications.
Advantages and Disadvantages of Bioengineered Skin Substitutes:
Gene delivery to wounds includes traditional approaches such as
viral vectors and plasmid delivery or, more recently,
electroporation and microseeding.
Delivering extra genes into the wound bed presents the challenge
of expression of the necessary signals to turn the genes on and off
at appropriate times so that dysregulated, hypertrophic, and
abnormal healing does not occur.
Although gene therapy replaces missing or defective genes, most
acute wounds already have and express the necessary genes for
successful healing and the wound environment produces signals
adequate to the activation of these genes.
Another approach is to deliver multiple genes coding for proteins
that can act synergistically and even in a timed sequence, as
would occur during normal healing.
The feasibility of applying bone marrow-derived, umbilical cord-
derived, adipose-derived, and epidermal stem cells that can
differentiate into various cells that participate in the wound
healing response also has been documented.

Growth Factor Therapy

Growth factors for clinical use may be either recombinant or
homologous/autologous.
Autologous growth factors are harvested from the patient’s own
platelets, yielding an unpredictable combination and
concentration of factors, which are then applied to the wound.
This approach allows treatment with patient-specific
factors at an apparently physiologic ratio of growth factor
concentrations.
Recombinant molecular biologic means permit the purification of
high concentrations of individual growth factors.
Current FDA-approved formulations, as well as those used
experimentally, deliver concentrations approximately 103 times
higher than those observed physiologically.
At present, only platelet-derived growth factor BB (PDGF-BB) is
currently approved by the FDA for treatment of diabetic foot
ulcers.

Gene or Cell Therapy Mirri odria uepi dreji zgienisi, separ hen mibajyr udir anogrosa
Direct access to the open wound bed, which characterizes anehussi!
almost all chronic wounds, has facilitated this therapy. “Some old wounds never truly heal, and bleed again at the
slightest word”

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