Inflammation (days 1–10) – PMNs, macrophages; epithelialization (1–2 mm/day)

  Proliferation (5 days–3 weeks) – fibroblasts, collagen deposition, neovascularization, granulation tissue formation; type III collagen replaced with type I

  Remodeling (3 weeks–1 year) – decreased vascularity

•  Net amount of collagen does not change with remodeling, although significant production and degradation occur

•  Collagen cross-linking occurs

  Peripheral nerves regenerate at 1 mm/day

  Order of cell arrival in wound

•  Platelets

•  PMNs

•  Macrophages

•  Lymphocytes (recent research shows arrival before fibroblasts)

•  Fibroblasts

  Macrophages are essential for wound healing (release of growth factors, cytokines, etc.)

  Fibronectin – chemotactic for macrophages; anchors fibroblasts

  Fibroblasts – replace fibronectin-fibrin with collagen

  Predominant cell type by day

•  Days 0–2 – PMNs

•  Days 3–4 – macrophages

•  Days 5 and on – fibroblasts

  Platelet plug – platelets and fibrin

  Provisional matrix – platelets, fibrin, and fibronectin

  Accelerated wound healing – reopening a wound results in quicker healing the 2nd time (as healing cells are already present there)

  Epithelial integrity – most important factor in healing open wounds (secondary intention)

•  Migration from hair follicles (#1 site), wound edges, and sweat glands

•  Dependent on granulation tissue in wound

•  Unepithelialized wounds leak serum and protein, promote bacteria

  Tensile strength – most important factor in healing closed incisions (primary intention)

•  Depends on collagen deposition and cross-linking of collagen

  Submucosa – strength layer of bowel

•  Weakest time point for small bowel anastomosis – 3–5 days

  Myofibroblasts (smooth muscle cell–fibroblast; communicate by gap junctions)

•  Involved in wound contraction and healing by secondary intention

•  Perineum has better wound contraction than leg

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