Repair of damaged tissues happens by two processes

1. Regeneration e.g liver cells

• Different tissues consistent of continuously dividing labile cells (epithelia, hepatocytes), normally quiescent stable cells capable of proliferation (more parenchymal organs) and non-dividing permanent cells (neurons, skeletal and cardiac muscle). The regenerative capacity of a tissue depends on the proliferative potential of its constitutive cells.
• Continuously dividing labile tissue contain stem cells that can replenish lost cells
• Cell proliferation is stimulated by growth factors (produced by macrophages) and from the ECM. Proliferation of residual cells is supplemented by development of mature cells from stem cells.
• The Liver: Up to 90% of the liver can be regenerated by proliferation of residual hepatocytes + stem cells such as those residing in the Canals of Herring

2. Scar formation:

• If repair cant be accomplished by regeneration alone, connective fibrous tissue is laid down instead.
• Macrophages(more M2-type) play a central role by secreting cytokines that stimulate fibroblast proliferation and connective tissue synthesis and deposition. Macrophages produce TGF-β which is the most important cytokine for the synthesis and deposition of connective-tissue proteins. TGF-β stimulates fibroblast migration and proliferation, increases synthesis of collagen and fibronectin, and decreases degradation of the ECM by inhibiting metalloproteinases.
• ECM deposition depends on the balance between fibrogenic agents and MMPs (matrix metalloproteinases) that digest ECM, as well as TIMPs (shut down MMPs)
• Keloid scarring: when scar tissue grows beyond the boundaries of the original wound and does not regress
• If fibrosis develops in a tissue space occupied by an inflammatory exudate, it is called organisation (e..g organising pneumonia)

Vascular response to injury

Angiogenesis: sprouting of new blood vessels from existing ones, promoted by VEGF, FGF2, PDGF, angipoetin,

What is the timeline for events in wound healing by primary intention and secondary intention?

Primary intention healing:

• Immediate: formation of blood clot
• 24 hours: neutrophils at incision margins
• 24-48 hours epithelial cells from both edges proliferate to form a thin continuous layer
• Day 3: Neutrophils replaced by macrophages; early granulation tissue appears; initiation of angiogenesis and fibroblasts start proliferating and migrating to the site and lay down collagen fibres
• Day 5: Maximum neovascularisation and granulation tissue(fibroblasts ++, new delicate capillaries, loose ECM, macrophages, mast cells); collagen and ECM deposition
• Day 14: continued collagen deposition and fibroblast proliferation
• Day 30: complete scar formation (granulation tissue replaced by collagen)

What factors influence wound healing?

• Infection
• Diabetes
• Nutritional status
• Aging
• Steroids (inhibit TGF-β)
• Mechanical factors (pulling wounds apart)
• Poor perfusion
• Location of injury; e.g. organs with high regenerative capacity like the liver, areas with poor perfusion