Tissue Repair and Regeneration

• Repair is the replacement of damaged tissue by living tissue.

Types of Repair

• Regeneration involves replacing destroyed tissue with the same type of cells, such as repairing a bone fracture.
• Classification depends on the cells' proliferative capacity.
• Labile cells have a good capacity for continuous proliferation to replace aging cells, like stratified squamous epithelium of skin and columnar epithelium of the GIT.
• Stable cells do not proliferate under normal conditions but can when needed. Examples include parenchymatous cells (liver, pancreas, renal tubules) and mesenchymal cells (fibroblasts, chondroblasts, and osteoblasts).
• Permanent cells cannot proliferate at all, such as muscle cells and nerve cells.
• Repair by fibrosis replaces destroyed tissue with granulation tissue, which matures into fibrosis, occurring when the injury is severe or persistent.

Granulation Tissue

• Granulation tissue is red, granular soft, painless, and bleeds easily, forming in the gap of healing wounds.
• It consists of fibroblasts surrounded by collagen, newly formed blood vessels, scattered macrophages, and other inflammatory cells.
• Scar formation occurs after excess collagen deposition and obliteration of the capillaries.

Microscopic Section of Granulation Tissue

• Many thin-walled capillaries are lined by swollen endothelial cells.
• The background is a homogenous pink edematous stroma containing spindle-shaped fibroblasts, collagen fibers, and few inflammatory cells.

Characteristics of Granulation Tissue

• Appears light red or dark pink and is perfused with new capillary loops.
• Soft to the touch.
• Appearance is moist and granular with punctate hemorrhages.
• Pulsatile upon palpation.
• Painless when healthy.

Mechanism of Granulation Tissue Formation

• During the proliferative stage of healing, re-epithelialization and replacement of the clot by granulation tissue occur simultaneously.
• Cytokines, growth factors, interleukins, and angiogenesis factors are active during this highly cellular stage.
• Fibroblasts function to synthesize collagen and the extracellular matrix, initially consisting of type-III collagen (weaker) replaced by type-I collagen (stronger).
• Leukocytes and macrophages phagocytize old or damaged tissue and protect the healing tissue from pathogenic infection.
• Endothelial cells quickly grow from older, intact blood vessels (angiogenesis), branching systematically and forming anastomoses.
• Granulation tissue grows from the base of the wound and can fill any size wound

Fate of Granulation Tissue

• Granulation tissue is gradually replaced by fibrous scar, with type III collagen slowly replaced by type I collagen, increasing tensile strength.
• Errors in granulation tissue formation can lead to chronic wound formation.
• Foreign bodies at the wound site can also result in persistent granulation tissue and poor wound healing, with excess macrophages, fibroblasts, and capillaries reacting around the foreign material.

Wound Healing Features of Primary Intention

• Healing occurs in clean surgical wounds with minimal tissue destruction.
• Minimal bleeding and no bacterial infection.
• Good apposition of wound edges.

Steps of Healing by Primary Intention

• Initial Hemorrhage: The wound cavity fills with blood clot.
• Inflammation (24 hours): PNLs infiltrate the blood clot.
• Epithelial Changes (48 hours): Epithelial cells from wound edges proliferate.
• Early Granulation Tissue (3rd day): Macrophages replace PNLs, stimulating the ingrowth of fibroblasts and angioblasts, which start forming collagen type III. Epidermal cells form a bridge to seal off the defect.
• Fully Developed Granulation Tissue (4-6 days): Neovascularization (angiogenesis), new formation of blood vessels, and granulation tissue fills the wound gap.
• Scar Formation (2nd week): Inflammation subsides with fibroblastic proliferation and collagen deposition continuing.
• Remodeling of the Scar (by the end of 1st month): Reshaping or reconstruction and increased tissue strength occur.

Wound Healing Features of Secondary Intention

• Occurs in gaping wounds with marked tissue destruction.
• Bleeding and infection.
• Poor apposition of wound edges.
• Healing by secondary intention has the same steps as primary intention, but:
  • Inflammatory response is greater.
  • Formation of abundant granulation tissue.
  • Epithelization takes more time according to the wound gap.
  • Excessive fibrosis and wound contraction.
  • More liability to infection and complications.

Differences Between Primary and Secondary Intention

• Primary wound edges are clean; secondary wound edges are irregular.
• Primary has minimal inflammatory response; secondary has a marked inflammatory response.
• Primary has minimal granulation tissue; secondary has abundant granulation tissue.
• Epithelization takes less time in primary and more time in secondary.
• Fibrosis and contraction are minimal in primary and marked in secondary.
• Infection and complications are less frequent in primary and more frequent or marked in secondary.

Factors Affecting Wound Healing

• Local factors include the size and site of the wound, infection, foreign bodies, and blood supply. Poor blood supply delays repair.
• Systemic factors include age (healing is more rapid in young people due to more vascularity), nutritional disorders (anemia and malnutrition delay repair), metabolic disorders, chronic debilitating diseases, diabetes (increases susceptibility to infection), and drugs (steroids and cytotoxic drugs delay repair).

Complications of Wound Healing

• Infection.
• Sinus: Blind duct lined by epithelium between the wound and external surface.
• Fistula: Duct lined by epithelium between the wound and a hollow organ.
• Ulcer: Loss of continuity of surface epithelium.
• Keloid: Excessive granulation tissue and scar formation.
• Incisional hernia.
• Cicatrization: Scar on flexures that interfere with movement.
• Implantation (epidermal) cyst.
• Malignant transformation: Squamous cell carcinoma.