1. Wound Healing Wallace Medina, MD, FPCS,FPSGS,FPALES

4. Types of Wound Closure Primary or first intention Secondary or spontaneous Tertiary or delayed primary

5. Phases of Wound Healing A. Inflammatory or reactive phase - immediate response to injury - goals: hemostasis, debridement , sealing of the wound

9. Growth factors: FGF, VEGF Cytokines: TNF- Nitric oxide Angiogenesis Growth factors: TGF-, EGF, PDGF Cytokines: TNF-, IL-1, IFN- Enzymes: arginase, collagenase Prostaglandins Nitric oxide Matrix synthesis Growth factors: PDGF, TGF-, EGF, IGF Cytokines: TNF-, IL-1, IL-6 Fibronectin Cell recruitment and activation Collagenase, elastase Débridement Reactive oxygen species Nitric oxide Phagocytosis Mediators Activity Activities During Wound Healing Macrophage

10. Table 8-2 Growth Factors Participating in Wound Healing Stimulates fibroblasts, keratinocytes, chondrocytes, myoblasts Mitogenesis: mesoderm and neuroectoderm Stimulation of angiogenesis (by stimulation of endothelial cell proliferation and migration) Fibroblasts, endothelial cells, smooth muscle cells, chondrocytes Fibroblast growth factor (FGF) Stimulation of collagen synthesis Stimulation of angiogenesis Mitogenesis: fibroblasts, smooth muscle cells Chemotaxis: fibroblasts, smooth muscle, monocytes, neutrophils Platelets, macrophages, monocytes, smooth muscle cells, endothelial cells Platelet-derived growth factor (PDGF) Cellular and Biological Effects Wound Cell Origin Growth Factor

11. Table 8-2 Growth Factors Participating in Wound Healing TGF- 3 inhibits scar formation Stimulates angiogenesis TGF- 1 stimulates wound matrix production (fibronectin, collagen glycosaminoglycans); regulation of inflammation Platelets, T lymphocytes, macrophages, monocytes, neutrophils Transforming growth factor- alpha (TGF- alpha ) (3 isoforms: 1 , 2 , 3 ) Mitogenic and chemotactic for epidermal and endothelial cells Homology with EGF; binds to EGF receptor Keratinocytes, platelets, macrophages Transforming growth factor- B (TGF- B ) Stimulates proliferation and migration of all epithelial cell types Platelets, macrophages, monocytes (also identified in salivary glands, duodenal glands, kidney, and lacrimal glands) Epidermal growth factor (EGF) Significant homology with FGF; stimulates keratinocytes Keratinocytes, fibroblasts Keratinocyte growth factor (KGF)

12. Table 8-2 Growth Factors Participating in Wound Healing Stimulates macrophage differentiation/proliferation Macrophage/monocytes, endothelial cells, fibroblasts Granulocyte-macrophage colony-stimulating factor (GM-CSF) Stimulates angiogenesis Mitogen for endothelial cells (not fibroblasts) Similar to PDGF Macrophages, fibroblasts, keratinocytes Vascular endothelial growth factor (VEGF) Increase membrane glucose transport Promotes protein/extracellular matrix synthesis Likely the effector of growth hormone action Platelets (IGF-1 in high concentrations in liver; IGF-2 in high concentrations in fetal growth) Insulin-like growth factors (IGF-1, IGF-2)

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

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

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

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

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

23. Factors affecting wound healing

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

26. Types of Wound Dressing Non Adherent Absorptive Occlusive Creams/ointment/solution

27. Covering a wound with a dressing mimics the barrier role of epithelium Table 8-7 Desired Characteristics of Wound Dressings Convenience Cost-effectiveness Nontraumatic removal Safety Permeability to gas Nonallergenic and nonirritating Odor control Pain control Conformability Promote wound healing (maintain moist environment)