Wound Healing

2.2.07

Terms
• Resolution e.g. lobar pneumonia.
• Repair.
• Regeneration.
• Organisation.
• Replacement.

Regeneration
• Labile cells.
-Epithelia, blood cells.
• Stable cells.
-Organs with "no" stem cells e.g. liver.
• Permanent cells.
-Neurones in CNS.
-Muscle (skeletal and cardiac).
• Role of stem cells in regeneration.

Regeneration of stable cells
• Mitogenic signals.
-Autocrine.
-Paracrine.
-Endocrine.
• Receptors.
• Signal transduction.
• DNA-binding proteins.
• Framework required.

Organisation
• Exudate.
• Fibroblasts and blood vessels.
• Collagenous scar.
• E.g.
-Peritoneal adhesions.
-Pericarditis.
-Pulmonary fibrosis.

Wound healing
• Primary intention.
-Clean surgical wound firmly apposed.
• Secondary intention.
-Large, denuded wound e.g. abrasion, burn.

Events in wound
• Haemorrhage → clotting.
-Platelets.
-Fibrin(ogen) and fibronectin.
• Epidermis.
-Cells migrate over wound.
§Marginal keratinocytes interact with fibronectin.
§Cells proliferate (start 12 hours after wounding).

Events in wound - dermis
• Neutrophils → wound (12-24 hours).
• Macrophages → wound (24 hours+).
-Demolition.
-Angiogenesis.
§Vascular buds; leaky, fragile capillaries.
§Granulation tissue.
-Stimulation of fibroblasts.
§VEGF increases permeability and leakage.
§Macrophages produce PDGF, TGF-β and FGF.
-Collagen maturation.

Growth factors
• EGF (epidermal).
-Also stimulates mesenchyme.
-Mouth and GIT, but not skin wounds.
• PDGF (platelet-derived).
-Mitogenic, chemoattractant (chemotaxis).
• FGF (basic fibroblast).
-Angiogenesis.
-Cell migration.
-Haemopoiesis.
-Muscle and lung maturation.
• VEGF (vascular endothelial).
-Vasculogenesis in embryo.
-Angiogenesis (tumours, healing).
-Varieties: -C acts on lymphatics.
• TGF-α (transforming).
-Homology to EGF - found in wounds.
• TGF-β.

Cytokines
• Produced by inflammatory cells.
-IL-1.
§Stimulates fibroblasts to divide, synthesise collagen and also produce collagenase.
-TNF-α.
§Tumour cell killing.
§Wasting.
§Inflammatory diseases/conditions.
§Stimulates new blood vessels.

Collagen and extracellular matrix
• ECM.
-Collagens and elastins.
-Adhesives: fibronectin, laminin.
-Proteoglycans and hyeluronan.
• Collagen.
-14 types.
§Types 1-3 fibrillar.
§Type 4 in basement membrane.

Wound strength regained
• 10% at 1 week (stitches out).
• Increases to 70% by 5 weeks and plateaus at ~ 80%.
• GIT anastomosis 90% by 8 days.

Large wounds
• Secondary intention.
-More granulation tissue.
-Wound contraction.
§Myofibroblast (contains actin, but no myosin).
§Fibronectin molecules bridge myofibroblasts and collagen fibres.

Factors limiting wound healing
• Systemic.
-Lack of:
§Protein.
§Vitamins (A, C).
§Zinc.
-Steroids.
-Age (?)
-Diabetes.
• Local.
-Lack of immobilisation.
-Foreign body/infection.
-Blood supply (including venous drainage) e.g. leg ulcers.
-Poor oxygenation.
• Complication: keloid scar.

Healing of bone
• Fracture → haemorrhage.
-Inflammation.
-Necrosis locally.
-Granulation tissue.
• Provisional callus.
-Woven bone with cartilage islands.
• External callus.
• Remodelling.
-Possible sources of failure.