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

Secondary Wound Healing

Secondary Wound Healing

Secondary Wound Healing

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 TNFa Fibroplasia: ILs, EGF and TNF Synthesize NO Secrete collagenases

Inflammatory Phase

Inflammatory Phase

Inflammatory Phase

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 (differentiation)

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

Proliferative Phase

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

Maturation Phase

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 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

Vitamin E

 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

 Smoking

Factors in Wound Healing

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 Healing

Ehlers-Danlos Syndrome
Connective tissue abnormalities due to defects:

Inherent strength Elasticity Integrity Healing properties

Syndromes Associated with Abnormal Wound Healing

Ehlers-Danlos Syndrome
Four major clinical features

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

Hypertropic Scar

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

Keloid Scar

Keloid Scar

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 III B. Type V C. Type VII D. Type XI
A.

 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 EhlersDanlos 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