Tissue Repair and Healing

• Repair, also known as healing, is the replacement of damaged tissues with healthy, new tissue.
• The type of repair depends on the type of cells and their ability to divide and proliferate

Types of Repair

• Repair by regeneration refers to the replacement of damaged cells with new healthy cells of the same type.
• Repair by fibrosis is the replacement of damaged cells by granulation tissue, which matures into fibrous tissue

Factors Determining the Type of Repair

• Severity of damage (stroma)
• Blood supply
• Persistent infection or presence of a foreign body
• Ability of tissue to proliferate

Types of Cells

• Labile cells can proliferate continuously and have good power of division.
• Labile cells include stratified squamous epithelium of skin/mucous membranes, transitional epithelium of the urinary tract, columnar epithelium, and hemopoietic/lymphoid cells.
• Stable cells can proliferate when needed, have limited power of division, and undergo regeneration after minor injury but fibrosis after major injury.
• Stable cells include parenchymatous cells of the liver, pancreas, glands, and renal tubules, as well as mesenchymal cells like osteoblasts, chondroblasts, and fibroblasts.
• Permanent cells cannot proliferate and include muscle cells (cardiac and skeletal) and nerve cells (brain/spinal cord).

General Factors Affecting Repair

• Age
• Nutritional deficiency
• Drugs
• Endocrine diseases

Mechanisms of Repair

• Growth factors help cell division, migration, proliferation, and DNA synthesis, are released from damaged cells, platelets, macrophages and lymphocytes, and include epidermal growth factor (EGF) and platelet-derived growth factor (PDGF).
• Cell-to-cell interactions
• Cell-to-matrix interactions

Repair by Regeneration Examples

• Skin Regeneration
• Epidermis alone regenerates easily
• Dermis heals by granulation tissue (fibrosis)
• Liver cells (stable cells)
• Mild cell injury with intact fibrous framework allows perfect regeneration.
• Severe cell injury with destroyed fibrous framework leads to irregular fibrosis and liver cirrhosis.

Repair in the Nervous System

• Central Nervous System (permanent cells)
• No regeneration occurs; necrotic cells are removed by microglia and replaced by proliferating neuroglia cells, which is called gliosis.
• Peripheral Nerves: Regeneration can occur
• Nerve cells swell, Nissl granules disappear, nuclei become eccentric, and myelin sheath/axis cylinder disintegrate after nerve injury.
• Schwann cells proliferate and form continuous neurilemmal tubes.
• New axons grow from the proximal end and reformation of the myelin sheath occurs.
• If cut nerve ends are not in direct opposition, Schwann cells and growing axons mix, forming a painful mass called traumatic (stump or amputation) neuroma.

Healing of Bone Fracture

• A hematoma forms at the fracture site with acute inflammation, and growth factors are released.
• The hematoma is invaded by fibroblasts, osteoblasts, and new capillaries to form a soft callus or procallus.
• The procallus converts to fibro-cartilaginous callus, then osteoid callus, and finally hard bony callus by progressive endochondral ossification.
• Unneeded callus is removed by osteoclasts, followed by remodeling of the intermediate callus with deposition of calcium phosphate and carbonate.
• Bone marrow regenerates later.

Bone Union Failure Causes

• Faulty immobilization leading to fibrous union
• Infection
• Impaired blood supply
• Interposition of soft tissue
• Nutritional disturbance

Examples of Repair by Granulation (Healing by Fibrosis)

• Granulation tissue, consisting of proliferating fibroblasts and anastomosing capillaries, matures into fibrous tissue through:
• Fibrogenesis: migration and proliferation of fibroblasts at the injury site.
• Angiogenesis (Neovascularization): migration and proliferation of endothelial cells leading to anastomosing capillary loops.
• Fibroblasts secrete extracellular matrix proteins and collagen types I and III.
• Remodeling and maturation of granulation tissue by progressive collagen synthesis, resorption of capillaries, and myofibroblast contraction, leading to mature scar formation.

Healing of Wounds

• Primary union of wounds (Healing by first intention) occurs in non-infected incised wounds with minimal tissue destruction and approximated edges via surgery.
• Basal cells proliferate, crossing the gap to form the whole epidermis.
• Macrophages start phagocytosis on day 3.
• The gap fills with granulation tissue on days 4-5 without skin adnexa.
• Secondary union of wounds occurs in infected wounds with excess tissue destruction and gaping edges typically due to an accident.
• Basal cells proliferate but cannot cross the gap until it is filled by granulation tissue infiltrated by polymorphs and macrophages.
• Phagocytosis takes a long time.
• The basal layer covers the thick granulation tissue forming the whole epidermis without skin adnexa.

Possible Wound Healing Complications

• Chronic ulcer: Persistent loss of continuity of the covering that may affect skin or mucous membrane.
• Chronic sinus:A blind-ended tract between a deep wound (or abscess) and the skin, lined by infected granulation tissue due to the presence of a foreign body or infection.
• Chronic fistula involves a tract between two surface epithelia or hollow organs like the esophagus and trachea.
• Keloid is a large projecting scar covered by thin, stretched skin, caused by excessive repair and foreign body reactions to hairs, keratin, cotton, or fibers with unknown etiology.
• Interference with movements occurs due to scar contraction at joints.
• Implantation epidermoid cycts occur when epithelial cells get trapped in the dermis and proliferate, forming a cyst linked by stratified squamous epithelium filled with keratin.
• Malignant transformation may rarely develop in old scars, especially burns.