Tissue Repair, Regeneration, and Fibrosis

• Tissue repair is the replacement of damaged tissue by new, healthy tissue.

Types of Repair

• Classical types of repair include regeneration and fibrosis (gliosis in the CNS).
• Organization is another type of repair.

Factors Determining the Type of Repair

• Type of damaged cells
• The state of the supporting framework

Types of Damaged Cells

Labile Cells

• Continuously dividing cells that heal by regeneration if damaged.
• Examples include epidermis, mucous membranes (epithelial cells), and blood and lymphoid tissue.

Permanent Cells

• Cells that do not proliferate.
• Muscle cells heal by fibrosis if damaged.
• Nerve cells heal by gliosis if damaged.

Stable Cells

• Cells that can proliferate with limited capacity.
• They can heal by mixed regeneration and/or fibrosis if damaged.
• Parenchymal cells (hepatocytes, renal tubules, endocrine & exocrine glands), and mesenchymal cells (fibroblasts, osteoblasts, & chondroblasts) are examples.

Supporting Framework

• Intact framework leads to healing by regeneration.
• Destroyed framework results in disorganized cell growth and improper regeneration mixed with fibrosis, such as in liver cirrhosis.

Phases of Healing

• Cleaning phase involves the removal of necrotic debris by phagocytic cells.
• Proliferation phase involves cells responsible for repair proliferating to replace the damaged ones.
• Re-modeling phase involves maturation of the new tissue to simulate the original tissue.

Healing by Regeneration

• Regeneration is the replacement of damaged tissue by healthy tissue of the same kind.
• Labile cells and stable cells (with intact framework) heal by regeneration.

Examples of Healing by Regeneration

Healing in the Skin

• Damage to the epidermis or mucosa only leads to regeneration.
• Damage to the epithelium and sub-epithelium results in fibrosis with the loss of hair follicles, and sweat and sebaceous glands.

Healing of Liver Damage

• Intact supporting framework (mild damage) leads to regeneration.
• Destroyed framework (severe damage) results in cirrhosis, disorganized regeneration mixed with fibrosis, and loss of architecture.

Healing of Simple Bone Fracture

Cleaning Phase

• Macrophages and osteoclasts clean blood and necrotic debris between the fracture ends.

Proliferation Phase

• A modified type of granulation tissue develops between the fracture ends, formed of capillaries, fibroblasts, and osteoblasts.
• Capillaries provide O2 and nutrients to the active cells.
• Fibroblasts begin to form collagen of bone.
• Osteoblasts form the bone matrix.
• Early formation of osteoid (soft callus) unites the fracture ends, formed of internal, external, and intermediate callus.
• Late formation of hard callus (osseous) occurs as osteoblasts secrete alkaline phosphatase with mineral deposition in the soft callus, leading to complete union of the fracture.

Remodeling Phase

• Osteoclasts remove unnecessary internal and external callus.
• The remaining intermediate callus matures into lamellar bone, and bone marrow regeneration occurs.

Causes of Failure of Bony Union

• Poor immobilization of the fractured ends leads to fibrous union.
• Interposition of soft tissue (muscle or fascia) can cause non-union.
• Poor apposition results in mal-union.
• Other factors include delayed union, pathological fracture caused by bone disease, poor blood supply, infection, old age, and malnutrition.