OVERVIEW
Adult wound healing
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Proceeds through several overlapping stages
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Inflammation (days 0-6)
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Coagulation/ haemostasis
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Formation of thrombin-platelet plug (clot) adherent to type II collagen exposed by endothelial disruption​
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Platelet clot is a source of growth factors (PDGF, TGF-α and –β), inflammatory vasoactive and chemotactic cytokines, fibrinogen, fibronectin, thrombospondin and von Willebrand factor
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Fibrin-thrombin mesh traps more platelets to continue cycle
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Inflammation​
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Activation of mast cells and influx of neutrophils, macrophages and T-lymphocytes
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Initial vasoconstriction followed by active vasodilatation due to inflammatory mediators
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Proliferation (4 days to 3 weeks)
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Re-epithelialisaton​
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Marginal keratinocytes​ migrate over wound surface and convert into non-polarised cells expressing basal cytokeratins
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Restitution of the basement membrane induces to cells to adopt their previous morphology and form anchoring junctions with fibronectin
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Fibroplasia​
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Influx of fibroblasts over fibronectin scaffold​
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Fibroblasts synthesize type III collagen which forms granulation tissue
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Angiogenesis​
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Induced by VEGF​
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Remodelling (3 weeks to 18 months)
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When fibronectin predominates, fibroblasts actively synthesise hyaluronic acid and collagen​
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Caeses when collagen reaches an abundant level​
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Residual fibroblast mature into myofibroblasts and form cell-matrix and cell-cell contacts that contract the wound​
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Type III collagen is gradually replaced by type I collagen to normal type I:III ratio of 3:1
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Collagen becomes lamellar by activity of fibroblasts and collagenases
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The abundant capillaries regress
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Peak wound tensile strength is achieved at ~60 days and maximum of ~80% of unwounded skin strength
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Factors affecting wound healing
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May be attributed to a lowering of the oxygen concentration in the wound including radiotherapy and diabetes
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Oxygen tension of more than 40mmHg augments fibroblastc activity and is required for hydroxylation of proline and lysine residues to form cross linkages in the collagen α-chain
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Oxygen also facilitates cell-mediated killing of pathogens in the wound
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Patient factors
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Age​ - reduced cellular multiplication and production rate, and tensile strength and wound closure rates with age
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Nutrition
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Vitamin C - essential for hydroxylation of collagen​
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Vitamin E - neutralises lipid peroxidation caused by ionising radiation
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Minerals - zinc influences re-epithelialisation and collagen deposition
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Systemic illness - diabetes, etc​
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Smoking​
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Nicotine causes tissue vasocontriction​
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Cyanide impairs oxidative enzymes
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Carbon monoxide impairs oxygen carrying capacity of haemoglobin
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Drugs​
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Steroids - impaired macrophage and fibroblast function, reduced angiogenesis and contracture​
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NSAIDs - reduces prostaglandins
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Chemotherapy
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Genetic conditions - Ehlers-Danlos, progeria, etc​
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Wound factors​
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Infection​ - prolongs inflammatory phase
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​Oedema​ - reduces tissue perfusion
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Denervation - prone to ulceration
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Radiation
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Adjuncts to healing
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Negative wound pressure
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Unclear mechanism​
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Reduced oedema and interstitial pressure, improved tissue oxygenation and removing inflammatory exudate/ mediators and bacteria
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Hyperbaric oxygen
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Increases oxygen delivery to wounds​
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Growth factors
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Experimental
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Laser biostimulation
Foetal wound healing
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Regenerative process that occues with minimal of no scar formation
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Only occurs in the skin and bone of the hoetus
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Foetal wounds are rich in hyaluronic acid and fibronectin
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Healing is largely controlled by fibroblasts rather than macrophages
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Reduced levels of TGF-β, PDGF, bFGF
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Type III collagen is deposited in a more organised manner
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Tenascin is a modulator of cell growth and migration in foetal wounds