Wound healing

Wounds are a break in the skin and/or a disruption of the skin's normal barrier function. Wound healing is a step-wise cellular response involving fibroblasts, macrophages, endothelial cells, and keratinocytes that restore the structural and functional integrity of the skin. The four general stages of wound healing are exudative, resorptive, proliferative, and maturation. While the three initial stages take place within the first two weeks, the last stage proceeds over months. Many factors affect wound healing, including the size of the wound, tension on wound edges, the presence of foreign bodies or infection, and the baseline health and nutrition of the patient. In addition, chronic health conditions such as diabetes and peripheral vascular disease can slow the wound healing process. Delayed wound healing may lead to the formation of a chronic wound.

Risk factors for delayed wound healing: DID NOT HEAL

• Drugs (e.g., steroids, cytotoxics, and other immunosuppressive agents)
• Infections/Ischemia
• Diabetes
• Nutritional deficiency (e.g., iron-deficiency anemia)
• Oxygen (hypoxia)
• Toxins (e.g., alcohol consumption, smoking) ^[2]
• Hypothermia/hyperthermia
• Excessive tension on the wound edges
• Acidosis/Another wound
• Local anesthetics

Delayed wound healing or chronic wound formation

• Usually occurs in patients with multiple risk factors that cause slowing or failure to progress through one or more stages of wound healing
• The proliferative wound healing phase is delayed in individuals with copper and vitamin C deficiency.
• Zinc deficiency can delay wound healing because the collagenases responsible for collagen remodeling require zinc to function properly.

Scar formation

• Occurs when initial injury cannot be repaired solely by cell regeneration
• Cells that cannot be regenerated (e.g., due to chronic injury or because acute injury is too severe) are replaced by connective tissue.
• After 3 months, 70–80% of tensile strength is regained. ^[3]
• Maximum strength of scar tissue is approx. 80% of that of unwounded skin. ^[3]

Excessive scar

• Dysregulation of the wound healing process during the proliferative stage and maturation stage leads to excess fibroblast replication and collagen deposition.
• Molecular mechanisms ^{[4][5][6][7][8][9]}
  • Increased production of:
    • Certain isoforms of transforming growth factor-beta (primary mediator)
    • Connective tissue growth factor
    • Platelet-derived growth factor
    • Tissue inhibitors of metalloproteinases
  • Decreased production of:
    • Basic fibroblast growth factor
    • Metalloproteinases (e.g., collagenase)
    • Interleukin-10

Hypertrophic scar

• Cutaneous condition characterized by high fibroblast proliferation and collagen production that leads to a raised scar that does not grow beyond the boundaries of the original lesion.
• See “Hypertrophic scars.”

Keloid

• Skin lesions caused by high fibroblast proliferation and collagen production in excessive tissue response to typically small skin injuries
• Lesions grow beyond the original wound margins, leading to a ”claw-like” appearance.
• See “Keloid scars.”

Contracture

• Excessive proliferation in myofibroblasts during proliferative and maturation phases leads to contraction of the wound.
• Excessive contraction can reduce the functionality of the injured limbs or organs.
• Wounds that cross a joint (e.g., on the hands and fingers) are at high risk for causing functional deficits from contracture. Periodic exercise of the involved limb can help preserve normal function.