Healing & Repair Overview

Healing & Repair

• Healing is the body's response to injury to restore normal structure and function
• Healing involves two processes: regeneration and repair
• Regeneration involves the regeneration of parenchymal cells to restore original structure/function
• Repair occurs when tissues do not return to their normal structure and function, leading to scar formation
• Wound healing is a crucial mechanism for stopping bleeding, preventing infection, and restoring tissue integrity
• Wounds can be classified as tidy or untidy
• Tidy wounds involve clean, precise cuts
• Untidy wounds involve breaks due to injury (including torn, crushed tissues)

Types of Healing

• Primary union/healing by first intention occurs in surgically incised wounds
• These wounds are clean, uninfected, and have edges approximated by sutures
• Healing is characterized by limited death of epithelial and connective tissues
• Secondary union/healing by second intention occurs in untidy wounds
• These wounds have tissue loss and edges are not approximated surgically, resulting in a larger scar compared to a clean surgical incision

Regeneration

• Labile cells are actively dividing and undergo rapid regeneration in their normal state
• Stable cells do not divide actively under normal conditions; their division rate is variable in response to stimuli
• Permanent cells do not divide and cannot regenerate

Factors Controlling Regeneration

• Growth factors (e.g., EGF, FGF, IGF, PDGF)
• Hormones (e.g., ACTH, estrogen, growth hormone)
• Cell-cell interactions—signaling through integrins (specific cell membrane proteins)
• Contact with basement membranes
• Growth control is crucial in preventing cancer

Mechanisms Controlling Regeneration

• Growth factor receptor activation leads to intracellular signaling cascades
• Tyrosine kinases and other signaling pathways initiate protein synthesis and cell proliferation
• These cellular signaling cascades trigger growth regulatory proteins that control the cell cycle

Extracellular Matrix

• Collagen (types I, III, IV): scaffolding material
• Elastin
• Glycoproteins (e.g., fibronectin, tenascin)
• Proteoglycans (e.g., heparan sulfate proteoglycans)
• ECM supports tissue structure and function—it is vital for cellular function and wound healing

Skin Wounds

• Healing involves inflammatory, migratory, and proliferative phases
• Different wound types—e.g., surgical incisions, lacerations, pressure sores
• Complications of skin wound healing include infection, poor blood supply

Factors Influencing Wound Healing

• Local factors: wound type, size, location, infection, apposition, blood supply
• General factors: age, chronic diseases, nutritional deficiencies, medications (steroids)

Complications of Repair

• Insufficient fibrosis—wound dehiscence, hernia, ulceration
• Excessive fibrosis—cosmetic scarring (hypertrophic scars/keloids)
• Excessive contraction—limitation of joint movement (contractures), obstruction of tubes & channels (strictures)

Specialized Tissues Healing

• Muscles: heal by fibrosis
• Nerves: axons regenerate, but nerve cells do not regenerate (gliosis)

Bone Healing (Fracture Healing)

• Immediate: blood clot
• Hours: inflammation, neutrophils, macrophages
• Days: removal of dead tissue, granulation tissue formation, soft callus
• Weeks: calcium deposition, hard callus formation
• Months: remodeling, removal of irregular bone (osteoclasts)