Tissue Repair: Regeneration and Fibrosis

• Repair refers to the replacement of damaged tissue by living tissue

Types of Repair

• Regeneration replaces destroyed tissue with the same cells
• An example of regeneration is the repair of a bone fracture
• The proliferative capacity of cells determines their classification

Cell Types

• Labile cells have continuous proliferation to replace aging cells

• Examples of labile cells include stratified squamous epithelium of the skin and columnar epithelium of the gastrointestinal tract

• Stable cells do not proliferate under normal conditions, but will when needed

• Examples of stable cells are parenchymatous cells (liver, pancreas, renal tubules) and mesenchymal cells (fibroblasts, chondroblasts, and osteoblasts)

• Permanent cells cannot proliferate, such as muscle and nerve cells

Repair by Fibrosis

• Repair by fibrosis involves replacing destroyed tissue with granulation tissue, which matures into fibrosis

Granulation Tissue

• Granulation tissue is red, granular, soft, painless, and bleeds easily
• It forms in the gap of healing wounds
• It consists of fibroblasts surrounded by collagen, newly formed blood vessels, scattered macrophages, and some inflammatory cells
• Excessive collagen deposition and obliteration of capillaries leads to scar formation

Characteristics of Granulation Tissue

• Light red or dark pink due to new capillary loops
• Soft to the touch
• Moist and granular in appearance, due to punctate hemorrhages
• Pulsatile on palpation
• Painless when healthy

Wound Healing by Primary Intention

• Occurs in clean surgical wounds with minimal tissue destruction, minimal bleeding, and no bacterial infection, and with good apposition of wound edges

Steps of Healing by Primary Intention:

• Initial hemorrhage fills the wound cavity with blood clot
• Inflammation occurs within 24 hours as polymorphonuclear leukocytes (PNLs) infiltrate the blood clot
• Epithelial changes occur within 48 hours as epithelial cells from wound edges proliferate
• Early granulation tissue forms on the 3rd day as macrophages replace PNLs
• Macrophages stimulate the ingrowth of fibroblasts and angioblasts, which start forming collagen type III
• Epidermal cells form a bridge that seals off the defect
• Fully developed granulation tissue occurs within 4–6 days, with neovascularization, and granulation tissue fills the wound gap
• Scar formation occurs in the 2nd week as inflammation subsides, and fibroblastic proliferation and collagen deposition continues
• Remodeling of the scar occurs by the end of the 1st month

Healing by Secondary Intention

• Occurs in gaping wounds with marked tissue destruction, bleeding and infection, and poor apposition of wound edges
• The steps are similar to primary intention, but the inflammatory response is greater, and abundant granulation tissue forms
• Epithelization takes longer based on the wound gap
• Excessive fibrosis and wound contraction may occur alongside a higher risk of infection and complications

Factors Affecting Wound Healing

• Local factors include the size and site of the wound, infection and foreign bodies, and blood supply to the area
• Systemic factors include age, nutritional disorders (anemia and malnutrition), metabolic disorders, chronic debilitating diseases and diabetes, and drugs like steroids and cytotoxic drugs

Complications of Wound Healing

• Infection
• Sinus: A blind duct lined by epithelium between the wound and external surface
• Fistula: A 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 interferes with movement
• Implantation (epidermal) cyst
• Malignant transformation: Squamous cell carcinoma