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Slide 1: Wound Healing Wallace Medina, MD, FPCS,FPSGS,FPALES
Slide 2: Terminology • Wound repair- ability to restore normal function and structure • Regeneration – perfect restoration, no scar formation * All tissues proceed through the same series of events
Slide 3: Terminology • Acute wounds - orderly and timely reparative process •Chronic wounds – no restoration of functional integrity, stops at inflammatory phase
Slide 4: Types of Wound Closure Primary or first intention Secondary or spontaneous Tertiary or delayed primary
Slide 5: Phases of Wound Healing A. Inflammatory or reactive phase - immediate response to injury - goals: hemostasis, debridement , sealing of the wound
Slide 6: Phases of Wound Healing A. Inflammatory or reactive phase Events 1. Increase vascular permeability 2. Chemotaxis 3. Secretion of cytokines 4. Growth factor
Slide 7: Phases of Wound Healing A. Inflammatory or reactive phase Inflammatory cells PMN - Migration of PMN stops when wound contamination has been controlled - Don’t survive more than 24 hours - Increase contamination stimulates PMN resulting to delayed wound healing and destruction of tissues. - Not essential for wound healing
Slide 8: Phases of Wound Healing A. Inflammatory or reactive phase Inflammatory cells Macrophages - Orchestrate release of cytokines/ Process of wound healing/ release of growth factors - 24 – 48 hours - Source of TNF /interleukin 1, 6, 8
Slide 9: Macrophage Activity Phagocytosis Débridement Activities During Wound Healing Mediators Reactive oxygen species Nitric oxide Collagenase, elastase Cell recruitment and Growth factors: PDGF, TGF-, EGF, IGF activation Cytokines: TNF-, IL-1, IL-6 Fibronectin Matrix synthesis Growth factors: TGF-, EGF, PDGF Cytokines: TNF-, IL-1, IFNEnzymes: arginase, collagenase Prostaglandins Nitric oxide Growth factors: FGF, VEGF Cytokines: TNFNitric oxide Angiogenesis
Slide 10: Table 8-2 Growth Factors Participating in Wound Healing Growth Factor Wound Cell Origin Cellular and Biological Effects Chemotaxis: fibroblasts, smooth muscle, monocytes, neutrophils PlateletPlatelets, macrophages, derived growth monocytes, smooth muscle factor (PDGF) cells, endothelial cells Mitogenesis: fibroblasts, smooth muscle cells Stimulation of angiogenesis Stimulation of collagen synthesis Fibroblast growth factor (FGF) Fibroblasts, endothelial cells, smooth muscle cells, chondrocytes Stimulation of angiogenesis (by stimulation of endothelial cell proliferation and migration) Mitogenesis: mesoderm and neuroectoderm Stimulates fibroblasts, keratinocytes, chondrocytes, myoblasts
Slide 11: Keratinocyte growth factor (KGF) Epidermal growth factor (EGF) Keratinocytes, fibroblasts Platelets, macrophages, monocytes (also identified in salivary glands, duodenal glands, kidney, and lacrimal glands) Keratinocytes, platelets, macrophages Significant homology with FGF; stimulates keratinocytes Stimulates proliferation and migration of all epithelial cell types Transforming growth factor- B (TGF- B ) Homology with EGF; binds to EGF receptor Mitogenic and chemotactic for epidermal and endothelial cells Transforming growth factor- alpha (TGFalpha ) (3 isoforms: , , ) 1 2 3 Platelets, T lymphocytes, macrophages, monocytes, neutrophils Stimulates angiogenesis TGFstimulates wound 1 matrix production (fibronectin, collagen glycosaminoglycans); regulation of inflammation TGF3 inhibits scar
Slide 12: Table 8-2 Growth Factors Participating in Wound Healing Insulin-like growth factors (IGF-1, IGF-2) Platelets (IGF-1 in high concentrations in liver; IGF-2 in high concentrations in fetal growth) Likely the effector of growth hormone action Promotes protein/extracellular matrix synthesis Increase membrane glucose transport Vascular endothelial growth factor (VEGF) Macrophages, fibroblasts, keratinocytes Similar to PDGF Mitogen for endothelial cells (not fibroblasts) Stimulates angiogenesis Granulocyte-macrophage Macrophage/monocytes, endothelial colony-stimulating factor cells, fibroblasts (GM-CSF) Stimulates macrophage differentiation/prolife ration
Slide 13: Phases of Wound Healing A. Inflammatory or reactive phase Inflammatory cells Lymphocytes - Peak on 7th day - Affects fibroblast - Stimulate cytokines - Not essential for acute wound healing
Slide 14: Phases of Wound Healing B. Proliferative phase Goal: granulation tissue formation Events: 1. Angiogenesis 2. Fibroplasia 3. Epithelization
Slide 15: Phases of Wound Healing B. Proliferative phase Decrease collagen synthesis at 4 weeks after injury Epithelization begins hours after injury, sealed by clot then covered by epithelial eells, establishment of basement membrane
Slide 16: Phases of Wound Healing B. Proliferative phase Extracellular matrix - Scaffold for cellular migration - Composed of fibrin, fibrinogen, fibronectin, vitronectin Fibronectin and type 3 collagen = early matrix Type 1 collagen – wound strength later
Slide 17: Phases of Wound Healing B. Proliferative phase Collagen – 25% total protein Type 1 found in skin and bone - most common Adults – 80% type 1, 20% type 3 Neonates – type 3 predominates
Slide 18: Phases of Wound Healing B. Proliferative phase Hydroxylation results in stable triple stranded helix Vitamin C, TGF B, IgF 1, IgF 2- increase collagen synthesis Interferon Y , steroids – decreases collagen synthesis
Slide 19: Phases of Wound Healing C. Maturation phase Goal: scar contraction with collagen crosslinking, shrinking and loss of edema Events: 1. Scarring 2. Contraction 3. Remodeling of scar
Slide 20: Phases of Wound Healing C. Maturation phase Remodelling – wound strength increases 1-6 weeks, plateau 1 year after injury, tensile strength is only 30% Scar more brittle and less elastic
Slide 21: Phases of Wound Healing C. Maturation phase Wound contraction – centripetal movement of full thickness of skin Decreases amount of disorganized scar Wound contracture, physical restriction, limitation of function- result of wound contraction Appearance of stimulated fibroblast known as myofibroblast
Slide 23: Factors affecting wound healing
Slide 24: Proliferative Scar Collagen deposition versus Collagen degradation Keloid and hypertrophic scar-excessive collagen deposition Keloid – beyond borders , darkly pigmented individuals, genetic predisposition, clavicle, trunk, upper extremity, face
Slide 25: Wound Dressing Two concepts A.Occlusion - increase rate of epithelization – acidic pH, low oxygen tension- good environment for fibroblast and granulation tissue B. Absorption
Slide 26: Types of Wound Dressing Non Adherent Absorptive Occlusive Creams/ointment/solution
Slide 27: Table 8-7 Desired Characteristics of Wound Dressings Promote wound healing (maintain moist environment) Conformability Pain control Odor control Nonallergenic and nonirritating Permeability to gas Safety Nontraumatic removal Cost-effectiveness Convenience Covering a wound with a dressing mimics the barrier role of epithelium