Abigail E. Chaffin, M.D.

Assistant Professor of Plastic Surgery

Division of Plastic Surgery
Tulane University School of Medicine

History of Wound Healing

1700 BC Papyrus: Wound Healing
100 BC Egypt: Wound Healing Methods
1000 AD Gun Powder
1500 AD Hot Oil
20th Century Scientific Method

Wounds
Customize
Shotgun approach

not acceptable
No two patients OR

wounds are
identical

58y DM, Neuropathy: unaware

of R foot gangrene

Wounds

Wounds
Reconstructive

Ladder
Simple to

Complex

Formal Debridement, Elevation/ABIs

Appropriate IV ABX, Wound Vac, Skin Graft

Review of Wound Healing

Three basic types of healing
Primary
Delayed Primary
Secondary

Primary
Wound surfaces opposed
Healing without complications
Minimal new tissue
Results optional

Delayed Primary
Left open initially
Edges approximated 4-6 days later

Secondary
Surfaces not approximated
Defect filled by granulation
Covered with epithelium
Less functional
More sensitive to thermal and mechanical

injury

Three Phases of Wound

Healing

Inflammatory Phase
Proliferative Phase
Remodeling Phase

Three Phases of Wound

Healing
Inflammatory Phase
Proliferative Phase
Begins when wound is covered by

epithelium
Production of collagen is hallmark
7 days to 6 weeks
Remodeling Phase (Maturation Phase)

Inflammatory Phase
Hemostasis and Inflammation
Days 4 - 6
Exposed collagen activates clotting

cascade and inflammatory phase

Fibrin clot = scaffolding and concentrate
cytokines and growth factors

Inflammatory:
Granulocytes
First 48 hours
Attracted by inflammatory mediators
Oxygen-derived free radicals
Non-specific

Inflammatory:
Macrophages
Monocytes
attracted to area by complement
Activated by:
fibrin
foreign

body material
exposure to hypoxic and acidotic
environment
Reached maximum after 24 hours
Remain for weeks

Inflammatory:
Macrophages
Activated Macrophage:
Essential for progression onto

Proliferative Phase
Mediate:
Angiogenesis: FGF, PDGF, TGF-a&b and
TNF-a
Fibroplasia: ILs, EGF and TNF
Synthesize NO
Secrete collagenases

Three Phases of Wound

Healing
Inflammatory Phase
Proliferative Phase
Remodeling Phase

Proliferative Phase
Epithelization, Angiogenesis and

Provisional Matrix Formation

Begins when wound is covered by
epithelium
Day 4 through 14
Production of collagen is hallmark
7 days to 6 weeks

Epithelialization

Basal epithelial
cells at the wound
margin flatten
(mobilize) and
migrate into the
open wound
Basal cells at
margin multiply
(mitosis) in
horizontal direction
Basal cells behind
margin undergo
vertical growth

Proliferative: Fibroblast
Work horse of wound repair
Produce Granulation Tissue:
Main signals are PDGF and EGF
Collagen type III
Glycosaminoglycans
Fibronectin
Elastin fibers

Tissue fibroblasts become myofibroblasts

induced by TGF-b1

Wound Contraction
Actual contraction with pulling of edges

toward center making wounds smaller

Myofibroblast: contractile properties
Surrounding skin stretched, thinned
Original dermal thickness maintained
No hair follicles, sweat glands

Epithelialization/Contraction

Epithelialization

Collagen Homeostasis
After Wounding (Optimal Healing)
Days 3 - 7 week
Collagen

production begins
Days 7 42
Synthesis with a net GAIN of collagen
Initial increase in tensile strength due
to increase amount of collagen
Days 42+
Remodeling with No net collagen gain

Collagen
Normal Skin
collagen ratio 4 : 1 Type I/III

Hypertrophic Scar
collagen ratio 2 : 1 Type I/III

Three Phases of Wound

Healing
Inflammatory Phase
Proliferative Phase

Remodeling Phase

Maturation Phase
Random to organized

fibrils
Day 8 through years
Type III replaced by type I
Wound may increase in
strength for up to 2 years
after injury
Collagen organization
Cross linking of collagen

Impaired Wound Healing

Wound Healing
To treat the wound, you have to treat

the patient
Optimize the patient
Circulatory
Pulmonary
Nutrition
Associated diseases or conditions

Oxygen
Fibroblasts are oxygen-sensitive
PO2 < 40 mmHg collagen synthesis

cannot take place

Decreased PO2: most common cause of
wound infection
Healing is Energy Dependent
Proliferative Phase has greatly increased
metabolism and protein synthesis

Hypoxia:
Endothelium responds with

vasodilation
Capillary leak
Fibrin deposition
TNF-a induction and apoptosis

Edema
Increased tissue pressure
Compromise perfusion
Cell death and tissue ulceration

Infection
Decreased tissue PO2 and prolongs

the inflammatory phase

Impaired angiogenesis and
epithelialization
Increased collagenase activity

Nutrition
Low protein levels prolonged inflammatory phase
impaired fibroplasia
Of the essential amino
Methionine

is critical

Hydration
A well hydrated wound will epithelialize faster

than a dry one

Occlusive wound dressings hasten epithelial repair
and control the proliferation of granulation tissue

Temperature
Wound healing is accelerated at

environmental temperatures of 30C

Tensile strength decreases by 20% in
a cold (12C) wound environment
Denervation
Denervation has no effect on either

wound contraction or epithelialization

Diabetes Mellitus
Larger arteries, rather than the arterioles,

are typically affected

Sorbitol accumulation
Increased dermal vascular permeability
and pericapillary albumin deposition
Impaired oxygen and nutrient delivery
Stiffened red blood cells and increased
blood viscosity
affinity of glycosylated hemoglobin for
oxygen contributing to low O2 delivery
impaired phagocytosis and bacterial killing
neuropathy

Radiation Therapy
Acute radiation injury
stasis

and occlusion of small vessels

fibrosis and necrosis of capillaries
decrease in wound tensile strength
direct, permanent, adverse effect on
fibroblast
may be progressive
fibroblast defects are the central problem
in the healing of chronic radiation injury

Medications
Steroids

Stabilize

lysosomes and arrest of

inflammation response
inhibit both macrophages and neutrophils
interferes with fibrogenesis, angiogenesis,
and wound contraction
Also direct effect on Fibroblasts
Minimal endoplasmic reticulum
vitamin A
oral ingestion of 25,000 IU per day pre op
and 3d post op (not to pregnant women)
Restores inflammatory response and
promotes epithelializaton
Does not reverse detrimental effects on
contraction and infection

Nutritional Supplements
Vitamin C ( Ascorbic Acid)

is an essential cofactor in the

synthesis of collagen
excessive concentrations of ascorbic
acid do not promote supranormal
healing

Vitamin E

therapeutic

efficacy and indications

remain to be defined
large doses of vitamin E inhibit healing
increase the breaking strength of
wounds exposed to preoperative
irradiation

Nutritional Supplements
Glutamine
Enhance

actions of lymphocytes,
macrophages and neutrophils
Glycine
Inhibitory effect on leukocytes, might reduce
inflammation related tissue injury
Zinc
common constituent of dozens of enzymes
Influences B and T cell activity
epithelial and fibroblastic proliferation is
impaired in patients with low serum zinc levels

Factors
in
Wound
Healing
Smoking

1ppd = 3x freq of flap necrosis

2ppd = 6x freq of flap necrosis
Nicotine acts via the sympathetic system
vasoconstriction

and limit distal perfusion

1 cigarette = vasoconstriction > 90 min
Decrease proliferation of erythrocytes, macrophages and
fibroblasts
Smoke contains high levels of carbon monoxide
shifts

the oxygen-hemoglobin curve to the left

decreased tissue oxygen delivery

Syndromes Associated with

Abnormal Wound Healing
Cutis Laxa
Think defective elastin fibers
Congenital

AD, recessive or X-linked recessive

Acquired

Drug, neoplasms or inflammatory skin conditions

Ehlers-Danlos Syndrome
Think defective collagen metabolism
AD and recessive patters
10 phenotypes

Syndromes Associated
with
Abnormal Wound
Ehlers-Danlos Syndrome
Connective tissue abnormalities due to
Healing
defects:
Inherent strength
Elasticity
Integrity
Healing properties

Syndromes Associated
with
Abnormal
Wound
Ehlers-Danlos Syndrome
Four major clinical features
Healing
Skin

hyper-extensibility
Joint hyper-mobility
Tissue fragility
Poor wound healing

Electrostimulation
Electrical current applied to wounds
Increases migration of cells
109% increase in collagen
40% increase in tensile strength
1 to 50 mA direct or pulsed based on

wound

Hyperbaric Oxygen
Developed 1662 by Henshaw: Domicillium
Atmospheric pressure at sea level = 1 ATA

= 1.5ml O2/dL
Normal SubQ O2 tension is 30-50 mmHg.
SubQ O2 tension < 30 mmHg = chronic
wound

Excessive Healing
Hypertrophic Scars
Keloids

Keloids
Extends beyond original bounds
Raised and firm
Rarely occur distal to wrist or knee
Predilection for sternum, mandible and

deltoid
Rate of collagen synthesis increased
Water content higher
Increased glycosaminoglycans

Keloid Treatment
Triamcinolone injections
3-4 weeks
Cross linking modulated
Injections continued until no excess

abnormal collagen
Excise
Prevention during healing pressure and
injection

Keloid

Keloid

Questions

The proliferative phase of wound healing

occurs how long after the injury?

1 day
B. 2 days
C. 7 days
D. 14 days
A.

Which type of collagen is most important in

wound healing?
Type
B. Type
C. Type
D. Type
A.

III
V
VII
XI

The tensile strength of a wound reaches

normal (pre-injury) levels:

10 days after injury
B. 3 months after injury
C. 1 year after injury
D. never
A.

Which of the following is commonly seen in

Ehlers-Danlos syndrome?
A. Small bowel obstructions
B. Spontaneous thrombosis
C. Direct hernia in children

D. Abnormal scarring of the hands with

contractures.

Steroids impair wound healing by:

Decreasing angiogenesis and macrophage
migration
B. Decreasing platelet plug integrity
C. Increasing release of lysosomal enzymes
D. Increasing fibrinolysis
A.

Supplementation of which of the following

micronutrients improves wound healing in

patients without micronutrient deficiency?
A. Vitamin C
B. Vitamin A
C. Selenium
D. Zinc

Signs of malignant transformation in a

chronic wound include:

Persistent granulation tissue with bleeding
B. Overturned wound edges
C. Non-healing after 2 weeks of therapy
D. Distal edema
A.

The treatment of choices for keloids is:

Excision alone
B. Excision with adjuvant therapy (e.g. radiation)
C. Pressure treatment
D. Intralesional injection of steroids
A.

The major cause of impaired wound

healing is:
Anemia
B. Diabetes mellitus
C. Local tissue infection
D. Malnutrition
A.

Bradykinin, serotonin, and histamine in

wounds are released from:

Lymphocytes
B. Mast cells
C. Polymorphonuclear leukocytes
D. Platelets
A.

Platelets in the wound form a hemostatic

clot and release clotting factors to

produce:
Fibrin
B. Fibrinogen
C. Thrombin
D. Thromboplastin
A.

In a healing wound, metalloproteinases are

responsible for:
Establishing collagen cross-link
B. Glycosylation of collagen molecules
C. Incorporation of hydroxyproline into the collagen
chain
D. Initiating collagen degradation
A.

Severe cases of hidradenitis suppurativa in

the groin area are best managed by

excision of the involved area and?
Closure by secondary intension
B. Delayed primary closure
C. Primary closure
D. Split thickness skin grafting
A.

All of the following statements about keloids

are true except?

Keloids do not regress spontaneously
B. Keloids extend beyond the boundaries of the
original wound
C. Keloids or hypertrophic scars are best managed by
excision and careful reapproximation of the wound
D. Keloid tissue contains an abnormally large amount
of collagen.
A.

Thank You