Wound Healing and Scar Formation

Dermal Structure and Wound Healing

Normal Dermis Composition:

  • Collagen type one is the primary component.
    • Provides tensile strength.
    • Predominant in the reticular dermis.
  • Smaller proportion of collagen type three.
    • More pliable than type one collagen.
    • Found in higher concentrations in the papillary dermis.
  • Elastin fibers (illustrated in orange), often associated with fibrillin (red molecules).
    • Provide elasticity and recoil.
    • Fibrillin is essential for the structural integrity of elastin fibers.
  • Fibronectin as adhesive glycoproteins.
    • Binds to collagen, fibrin, and integrins.
    • Important for cell adhesion and migration during wound healing.
  • Glycosaminoglycans (GAGs) represented as green bottle brush structures.
    • Hydrate the dermis.
    • Support collagen and elastin fibers.
    • Include hyaluronic acid, chondroitin sulfate, and heparan sulfate.

Basement Membrane Zone:

  • Collagen type four forming a crosshatch structure.
    • Provides structural support.
    • Anchors the epidermis to the dermis.
  • Anchoring filaments.
    • Composed of laminin and other glycoproteins.
    • Mediate adhesion between the epidermis and dermis.
  • Glycosaminoglycans.
    • Contribute to the hydration and lubrication of the basement membrane zone.

Inflammatory Response:

  • Fibrin clot formation.
    • Provides a temporary matrix for cell migration.
    • Stops bleeding.
  • Fibrin network.
    • Stabilizes the wound.
    • Attracts inflammatory cells.
  • Fibronectin for adhesion and anchoring.
    • Facilitates the attachment of cells to the fibrin matrix.

Granulation Tissue:

  • Increased collagen type one.
    • Provides strength to the new tissue.
  • Minimal collagen type three.
    • Results in a less pliable tissue compared to normal dermis.
  • Higher levels of glycosaminoglycans (GAGs) compared to normal dermis.
    • Support cell migration and proliferation.
    • Maintain hydration.
  • Increased adhesive glycoproteins like fibronectin.
    • Promote cell adhesion and matrix organization.
  • Minimal or fragmented elastin.
    • Results in reduced elasticity in the granulation tissue.

Mature Scar Tissue:

  • Inactive fibroblasts.
    • Reduced metabolic activity compared to fibroblasts in granulation tissue.
  • Dense, cross-linked collagen.
    • Provides strength but reduces pliability.
  • Fragments of elastic tissue, but minimal elastin fibers.
    • Results in reduced elasticity in the scar tissue.
  • Extracellular matrix with predominant glycosaminoglycans.
    • Provides hydration and support.
  • Relatively few blood vessels (causing a paler appearance).
    • Reduced vascularity compared to normal dermis.

Wound Strength and Clinical Interventions

Collagen Deposition and Wound Strength:

  • Wound strength is largely dependent on collagen deposition.
    • Type one collagen provides the most tensile strength.
  • A two-year window exists to influence scar formation.
    • Early interventions can significantly improve scar outcomes.
  • Dermal clinicians perform treatments to improve scar outcomes.
    • Includes laser therapy, microneedling, and topical treatments.

Treatments for Scarring:

  • Treatments are most effective immediately after wound creation.
    • Early intervention minimizes collagen cross-linking and abnormal matrix deposition.
  • The treatment window can extend up to two years, depending on the wound's extent.
    • Deeper wounds may benefit from longer treatment durations.
  • After two years, re-wounding techniques (e.g., microneedling, fractional resurfacing) may be necessary to stimulate a new wound healing response.
    • These techniques induce controlled tissue damage to promote collagen remodeling.

Collagen Remodeling:

  • Collagen is continuously broken down by collagenase and replaced with new collagen.
    • Matrix metalloproteinases (MMPs) play a crucial role in collagen degradation.

Timeline of Wound Repair

  • Minutes: Clotting occurs.
    • Platelets aggregate and form a fibrin clot.
  • Hours: Acute inflammatory response.
    • Neutrophils and macrophages infiltrate the wound site.
  • Hours to Days: Proliferation and migration (fibroblastic stage).
    • Fibroblasts proliferate and synthesize collagen.
    • Keratinocytes migrate to cover the wound.
  • End of Fibroblastic Stage: Functional restoration (initial, weak).
    • New tissue is fragile and lacks significant strength.
  • Weeks to Years: Remodeling of collagen and other structures.
    • Collagen fibers are reorganized and cross-linked.

Primary vs. Secondary Intention Healing

Secondary Intention Wounds:

  • More pronounced inflammatory response.
    • Increased recruitment of immune cells.
  • Increased granulation tissue to fill the deficit.
    • Greater deposition of collagen and GAGs.
  • Greater risk of wound contraction.
    • Myofibroblasts contribute to wound closure by contraction.

Factors Affecting Wound Healing

Wound Strength:

  • Surgical wounds closed with sutures: ~70% strength of unwounded skin.
    • Sutures provide initial wound approximation and strength.
  • After suture removal (5-7 days): ~10% strength.
    • Wound relies on newly synthesized collagen for strength.
  • Rapid strength increase over the next four weeks.
    • Collagen deposition and cross-linking increase rapidly.
  • Plateau reached around three months: scar tissue ~70-80% strength of unwounded skin.
    • Collagen remodeling continues, but strength gains are limited.
  • The reason for incomplete restoration is still under research.
    • Factors may include collagen fiber alignment and composition.

Site of the Wound:

  • Skin wounds generally heal well.
    • High vascularity and cell turnover promote healing.
  • Brain wounds are more problematic due to limited cell division.
    • Neuronal regeneration is restricted.
  • Areas with skin folds may have a higher microbial load.
    • Increased risk of infection.

Tension on the Wound:

  • Forehead wounds tend to heal better (less movement) than cheek wounds (more movement due to talking and eating).
    • Less tension promotes better collagen alignment.

Wound Dehiscence:

  • Suture splitting leads to increased scarring because of collagen rearranging itself based on tension.
    • Abnormal collagen alignment contributes to scar formation.

Size of the Wound:

  • Smaller wounds heal faster than larger wounds.
    • Shorter distance for cells to migrate and proliferate.

Sterility of the Wound:

  • Infection delays wound healing, increases scar tissue, and causes complications.
    • Bacteria prolong the inflammatory phase and disrupt collagen synthesis.

Oxygen Status:

  • Hypoxic tissues heal poorly.
    • Oxygen is essential for collagen synthesis and angiogenesis.
  • Smoking vasoconstricts vessels, reducing oxygen to tissues and impairing healing.
    • Nicotine impairs blood flow and oxygen delivery.
  • Some surgeons refuse procedures like abdominoplasty on smokers due to the risk of compromised healing.
    • High risk of wound complications.

General Well-being:

  • Nutritional and metabolic factors are crucial for wound healing.
    • Adequate protein, vitamins, and minerals are necessary for collagen synthesis and cell proliferation.
  • Healthy individuals generally heal better.
    • Stronger immune response and better overall physiological function.

Age:

  • Young children heal faster than the elderly.
    • Higher cell turnover and more efficient collagen synthesis.
  • Wound healing is often delayed with age.
    • Reduced cell proliferation, decreased collagen synthesis, and impaired immune function.

Scar Formation:

  • Scar tissue is simplified and lacks elasticity.
    • Disorganized collagen fibers and reduced elastin content.
  • Loss of skin appendages (hair follicles, sweat glands) in scar tissue.
    • Scar tissue lacks the normal structure and function of skin.

Complications of Wound Healing

Ulcers:

  • Loss of epidermis down to the dermis (partial thickness wound).
    • Impaired barrier function and increased risk of infection.
  • Infected ulcers show pus and necrosis (eschar).
    • Bacteria and dead tissue delay healing.
  • Uneven wound surface impedes epidermal growth.
    • Keratinocytes cannot migrate properly over irregular surfaces.
  • Surgical debridement to clean the wound and remove necrotic tissue is often necessary.
    • Promotes healthy tissue regeneration.

Wound Dehiscence:

  • Sutures burst, and the wound reopens.
    • Loss of wound approximation and increased risk of infection.
  • Increases risk of infection.
    • Open wound is susceptible to bacterial contamination.
  • Example: median sternotomy (open heart surgery) incisions are prone to dehiscence due to tension from collagen alignment along Langer's lines.
    • Sutures may fail due to high tension.
  • These wounds often require heavy sutures or staples to withstand pressure.
    • Provides stronger wound closure.
  • High risk of hypertrophic scarring.
    • Abnormal collagen deposition leads to raised, thickened scars.

Evisceration:

  • Wound dehiscence with internal organs (e.g., intestines) protruding from the wound.
    • Surgical emergency requiring immediate intervention.

Contractures:

  • Collagen type one pulls tight, forming cross-links and distorting tissues.
    • Reduced tissue mobility and flexibility.
  • Example: capsule contracture after breast reconstruction with implants.
    • Implant becomes firm and distorted.
  • Contractures over joints can lead to joint flexion and dislocation if untreated.
    • Limits range of motion and can cause permanent joint damage.
  • Burns over joints require compression garments and physiotherapy to maintain range of motion and prevent contractures.
    • Prevents excessive collagen cross-linking and tissue distortion.

Scarring:

  • Atrophic scarring (e.g., acne scars).
    • Depressed scars due to collagen loss.

Keloid Scarring:

  • Excessive scar tissue formation extending beyond the original wound boundaries.
    • Firm, raised scars that can be itchy and painful.
  • Ears are prone to keloid formation (e.g., after ear piercing).
    • High tension and inflammation contribute to keloid development.
  • Darker Fitzpatrick skin types are more prone to keloid scarring.
    • Increased melanocyte activity and collagen synthesis.

Hypergranulation:

  • Excessive granulation tissue.
    • Raised, red tissue that prevents epithelialization.
  • Delays wound healing because the epidermis cannot grow