wound healing david a. jansen, md tulane university health science center division of plastic &...
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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