SURGERY 2011

Wound Healing Wallace Medina, MD, FPCS,FPSGS,FPALES 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
Nitric oxide Macrophage Activities During Wound Healing

Activity

Mediators

Phagocytosis

Reactive oxygen species

Acute wounds - orderly and timely reparative process Chronic wounds no restoration of functional integrity, stops at inflammatory phase

Dbridement

Collagenase, elastase

Phases of Wound Healing A. Inflammatory or reactive phase Events 1. 2. 3. 4. Types of

Cell recruitment and activation

Growth factors: PDGF, TGF-, EGF, IGF Cytokines: TNF-, IL-1, IL-6 Fibronectin

Increase vascular permeability Chemotaxis Secretion of cytokines Growth factor Wound Closure Primary or first intention Secondary or spontaneous Tertiary or delayed primary

Matrix synthesis

Growth factors: TGF-, EGF, PDGF Cytokines: TNF-, IL-1, IFNEnzymes: arginase, collagenase Prostaglandins Nitric oxide

Phases of Wound Healing A. Inflammatory or reactive phase - immediate response to injury - goals: hemostasis, debridement , sealing of the wound Inflammatory cells PMN Migration of PMN stops when wound contamination has been controlled Dont survive more than 24 hours Increase contamination stimulates PMN resulting to delayed wound healing and destruction of tissues. Not essential for wound healing Macrophages Orchestrate release of cytokines/ Process of wound healing/ release of growth factors 24 48 hours Source of TNF /interleukin 1, 6, 8 Lymphocytes th Peak on 7 day Affects fibroblast Stimulate cytokines Not essential for acute wound healing
Angiogenesis

Growth factors: FGF, VEGF Cytokines: TNFNitric oxide

Table 8-2 Growth Factors Participating in Wound Healing

Growth Factor Wound Cell Origin Cellular and Biological Effects

Platelet-derived Platelets, macrophages, growth factor monocytes, smooth muscle (PDGF) cells, endothelial cells

Chemotaxis: fibroblasts, smooth muscle, monocytes, neutrophils

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 ...chacha...

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Collagen 25% total protein

Keratinocyte growth factor (KGF) Epidermal growth factor (EGF) Keratinocytes, fibroblasts Significant homology with FGF; stimulates keratinocytes Stimulates proliferation and migration of all epithelial cell types

Type 1 found in skin and bone - most common Adults 80% type 1, 20% type 3 Neonates type 3 predominates

Platelets, macrophages, monocytes (also identified in salivary glands, duodenal glands, kidney, and lacrimal glands) Keratinocytes, platelets, macrophages

Transforming growth factor- B (TGFB )

Homology with EGF; binds to EGF receptor

Hydroxylation results in stable triple stranded helix Vitamin C, TGF B, IgF 1, IgF 2- increase collagen synthesis Interferon Y , steroids decreases collagen synthesis

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 TGF1stimulates wound matrix production (fibronectin, collagen glycosaminoglycans); regulation of inflammation TGF3 inhibits scar formation

C. Maturation phase Goal: scar contraction with collagen cross-linking, shrinking and loss of edema Events: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

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

Scarring Contraction Remodeling of scar 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 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

B. Proliferative phase Goal: granulation tissue formation Events: 1. Angiogenesis 2. Fibroplasia 3. Epithelization 4. Phases of Wound Healing 5. B. Proliferative phase 6. Decrease collagen synthesis at 4 weeks after injury 7. Epithelization begins hours after injury, sealed by clot then covered by epithelial eells, establishment of basement membrane 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

Factors affecting wound healing

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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 Wound Dressing Two concepts: A. Occlusion - increase rate of epithelization acidic pH, low oxygen tension- good environment for fibroblast and granulation tissue B. Absorption Types of Wound Dressing Non Adherent Absorptive Occlusive Creams/ointment/solution

Table 8-7 Desired Characteristics of Wound Dressings 1. Promote wound healing (maintain moist environment) 2. Conformability 3. Pain control 4. Odor control 5. Nonallergenic and nonirritating 6. Permeability to gas 7. Safety 8. Nontraumatic removal 9. Cost-effectiveness 10. Convenience

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