Wound HealingDAVID A. JANSEN, MD

TULANE UNIVERSITY HEALTH SCIENCE CENTER

DIVISION OF PLASTIC & RECONSTRUCTIVE SURGERY

Overview

Wound HealingPhasesFactors InfluencingAdjuncts to Wound HealingFetal wound healing

Wound CarePrinciplesDressings

Abnormal Scarring

Phases of Wound Healing Tissue Injury and Coagulation Inflammation

Remove devitalized tissue and prevent infection

Fibroproliferative Balance between scar

formation and tissue regeneration

Maturation/Remodeling Maximize strength and

structural integrity

Tissue Injury and Coagulation

Tissue Injury and Coagulation INJURY (Physical, antigen-antibody reaction, or

infection) Transient (5-10 minute) vasoconstriction

Slows blood flow, aid in hemostasis

Histamine mediated vasodilation and permeability changes

Vessels become lined with leukocytes, platelets and erythrocytes

Leukocyte migration into the wound

Hemostatic factors from platelets, kinins, complement, and prostaglandins send signals to initiate the inflammatory phase

Fibrin, Fibronectin, and plasma help form a clot and stop bleeding

Early Inflammation

Complement Cascade Activation

PMN infiltration 24-48 hours Phagocytosis and

debridement Stimulated by:

Complement components (C5a)

Formyl-methionyl peptide products from bacteria

Transforming Growth Factor (TGF)-b

Late InflammationMacrophage

Most critical cell type Predominates after 48-72 hours Attracted by:

Growth factors (PDGF, TGF-b) Complement Clotting components IgG Collagen and elastin breakdown products Leukotriene B4 Platelet factor IV

Late InflammationMacrophage Functions

Phagocytosis Primary producer of Growth Factors

(PDGF, TGF-b) Recruitment of fibroblasts (proliferative

phase) Proliferation of extracellular matrix by

fibroblasts Proliferation of endothelial cells

(angiogenesis) Proliferation of smooth muscle cells

This leads to the Fibroproliferative phase

Late InflammationLymphocyte

Appears at 72 hours Attracted by:

Interleukins IgGComplement products

Role yet to be determined

Fibroproliferative

Fibroblasts Migrate into the wound via ECM

Predominant cell type by day 7

Collagen synthesis Begins on days 5-7

Increases in linear fashion for 2 to 3 weeks

Angiogenesis Promoted by macrophages (TNF-alpha, FGF, VEGF)

Epithelialization Mitosis of epithelial cells after 48-72 hours

Modulated by growth factors (EGF, FGF, KGF)

FibroproliferativeExtracellular Matrix

Forms a scaffold for cell migration and growth factor sequestration (fibronectin, proteoglycans, collagen, etc.)

Collagen

Principle building block of connective tissue

1/3 of total body protein content

Collagen Types

Type 1Bones, skin, and tendons90% of total body collagenFound in all connective tissues

except hyaline cartilage and basement membranes

Type 2Hyaline cartilage, cartilage-like

tissues, and eye tissue

Collagen Types

Type 3 Skin, arteries, uterus, abdominal wall, fetal tissue Association with Type I collagen in varying ratios

(remodeling phase)

Type 4 Basement membranes only

Type 5 Basement membranes, cornea

Skin Type 1 : Type 3 ratio is 4:1 Hypertrophic scars/immature scars ratio maybe as

high as 2:1

Angiogenesis

Formation of new blood vessels throughout inflammatory and proliferative phase

Initiated by platelets TGF-b and PDGF

PMN Macrophages

TNF-alpha, FGF, VEGF Endothelial Cell

Forms new blood vessels

Epithelialization

Stimulated by Loss of contact-inhibition

Growth factors

EGF (mitogenesis and chemotaxis)KGF, FGF (proliferation)

Mitosis of epithelial cells 48-72 hours after injury behind leading edge

Epithelialization

Epithelium advances across wound with leading edge cells becoming phagocytic

Collagenase (MMP) Degrades ECM

proteins and collagen Enables migration

between dermis and fibrin eschar

Maturation/Remodeling

Longest phase: 3 weeks – 1 year Least understood phase Wound Contraction and Collagen

RemodelingWound Contraction

Myofibroblast

Fibroblasts with intracellular actin microfilaments

Maturation/Remodeling

Collagen RemodelingType 3 Collagen degraded and

replaced with Type 1Collagen degradation

achieved by Matrix Metalloproteinase (MMP) activity

Tensile Strength

Collagen is the main contributing factor

Rate of tensile strength All wounds begin to gain

strength during the first 14-21 days (~20% strength), variable then after

Strength PEAKs @ 60 days NEVER reaches pre-injury

levels

Most optimal conditions may reach up to 80%

Predominant Cell Types

Fetal Wound Healing

Lack of inflammation Absence of FGF and TGF-b

Regenerative process with minimal or no scar formation

Collagen deposition is more organized and rapid Type 3 Collagen (No Type 1)

High in hyaluronic acid

Factors That Influence Wound Healing

Oxygen Fibroblasts are oxygen-sensitive

Collagen synthesis cannot occur unless the PO2 >40mmHg

Deficiency is the most common cause for wound infection and breakdown

Hematocrit Mild to moderate anemia does not appear to have a

negative influence wound healing

>50% decrease in HCT

some studies report a significant decrease in wound tensile strength

Factors That Influence Wound Healing

Smoking Multifactorial in limiting wound healing

Nicotine

Vasoconstrictive -> decreases proliferation of erythrocytes, macrophages, and fibroblasts

CO

Decreases the oxygen carrying capacity of Hgb

Hydrogen Cyanide

Inhibits oxidative enzymes

Increases blood viscosity, decrease collagen deposition

A single cigarette may cause cutaneous vasoconstriction for up to 90 minutes

Factors That Influence Wound Healing

Mechanical Stress - tension Affects the quantity, aggregation, and orientation

of collagen fibers

Hydration Well hydrated wounds epithelialize faster

Environmental Temperature Healing is accelerated at temperatures of 30 C

Factors That Influence Wound Healing

Denervation No direct effect on epithialization or contraction

Loss of sensation and high collagenase activities in skin -> prone to ulcerations

Foreign Bodies (including necrotic tissue) Delay healing and prolong the inflammatory phase

Nutrition Delays increases in tensile strength

Edema May compromise tissue perfusion

Age Tensile strength and wound closure

rates decrease with age

Factors That Influence Wound Healing

Infection Prolongs inflammatory phase, impairs epithiliazation and angiogenesis Increased collagenolytic activity -> decreased wound strength and

contracture Bacterial counts > 105

Chemotherapy Decreases fibroblast production and wound contraction If started 10-14 days after injury, no significant long term problems, but

short term decreased tensile strength

Radiation Stasis and occlusion of small blood vessels Decreased tensile strength and collagen deposition

Systemic Diseases DM

Glycosylated RBCs Stiffened RBCs & Increased blood viscosity

Glycosylated WBCs impaired immune function

Renal Dz

Factors That Influence Wound Healing

Steroids Inhibit wound macrophages

Interfere with fibrogenesis, angiogenesis, and wound contraction

Vitamin A and Anabolic steroids can reverse the effects

Vitamin A Stimulates collagen deposition and increase

wound breaking strength

Factors That Influence Wound Healing

Vitamin C Essential cofactor in the synthesis of collagen

Deficiency is associated with immune dysfunction and failed wound healing (Scurvy)

High concentrations do not accelerate healing

Factors That Influence Wound Healing

Vitamin E Large doses inhibit wound healing

Decreased tensile strength

Less collagen accumulation

HOWEVER

Antioxidant that neutralizes lipid peroxidation caused by radiation Decreasing levels of free radicals and peroxidases increases the breaking strength of wounds exposed to preoperative radiation

Factors That Influence Wound Healing

Zinc Deficiency:

Impairs epithelial and fibroblast proliferation

Only accelerates healing when there is a preexisting deficiency

Factors That Influence Wound Healing

NSAIDs Decrease collagen synthesis an average of 45%

(ordinary therapeutic doses)

Dose-dependent effect mediated through prostaglandins

Wound Care General Principles

Cleaning and Irrigation Need at least 7psi to flush bacteria out of a wound

High pressure can damage wounds and should be reserved only for heavily contaminated wounds

Debridement Most critical step to produce a wound that will heal

rapidly without infection

Non-selective: Dakin solution, Hydrogen Peroxide, etc.

Useful in wounds with heavy contamination

When starts to granulate, start selective

Selective: sharp, enzymatic, autolytic, or biologic

Wound Care General Principles

Fundamentals of Surgical Wound Closure Incision should follow tension lines and natural folds in the skin

Gentle tissue handling

Complete hemostasis

Eliminate tension

Fine sutures and early removal

Evert wound edges

Allow scars to mature before repeat intervention (2 weeks to 2 months scar appearance is the worst)

Scar appearance depends more on type of injury than method of closure

Technical factors of suture placement and removal are more critical than type of suture used

Immobilization of wounds to prevent disruptions and excessive scarring (Adhesive strips after suture removal)

Wound Dressings

Over 2,000 commercially available

Red-Yellow-Black Classification Created to help choose appropriate dressings in

wounds healing by secondary intention

Treat worse colors first

Black -> Yellow -> Red

Abnormal Scarring

Hypertrophic Scars

Keloids

Widespread Scar

Comparison of Abnormal ScarsKeloid Hypertrophic

ScarWidespread Scar

Borders Outgrows wound borders

Remains within wound borders

Wide, flat, depressed

Natural History

Appears months after injury, rarely regresses

Appears soon after injury, regresses with time

Appears within 6 months of injury

Location Mostly face, earlobes, chest(Never eyelids or mucosa)

Flexor surfaces Arms, legs, abdomen

Etiologic Factors

Possible autoimmune, endocrine (puberty, pregnancy)

Tension Tension and mobility of wound edges

Treatment Intralesional steroids, compression therapy, silicone gel sheeting, radiation therapyOften worse after surgery alone

Same as Keloids but outcome usually more successful

Scar excision/layered closure

Comparison of Abnormal Scars

Keloid Hypertrophic Scar Widespread Scar

Genetics

Significant familial predilection

Low familial incidence

No inheritance pattern

Race African > Caucasian

Low racial incidence Not related to race

Sex Females > Males(Equal)

Equal Unknown

Age Most commonly 10-30 years

Any age, mostly less than 20 years

Any Age

Hypertrophic Scar

Keloids

Keloid: Treatments

No universally effective treatment, usually a combination of treatment types

Case by Case basis

Prevention (the best therapy) Avoid non essential surgery, minimal tension, use

cuticular monofilament synthetic sutures, avoid wound-lengthening techniques, and avoid incisions across joints

Keloids: Treatments

Surgery: Alone 50-80% reoccurrence rate Excision with early postoperative radiation (~25% reoccurrence

rate)

Excision with corticosteroids (50-70% reoccurrence rate)

Pressure- increase collagenase activity 24-30mm Hg, 18-24h/day for 4-6 months

Silicone gel sheeting- mechanism unclear (decrease movement/tension)

80-100% -improvement in hypertrophic scars

35%- improvement in keloids

Corticosteroids- intralesional Decreases collagen synthesis- unclear mechanism

Maybe used in conjunction with surgical excision

Complications- hypopigmentation, skin atrophy, telangiectasias

Keloid TreatmentRadiation

Most effective when given post operatively No advantage if given preoperatively

~25% reoccurrence rate when combined with excision

15-20 Gy administered over several doses (5-6)

Thank You