Abnormal wound healing: Clinic and treatment

Acute wound healing is the sum of cellular and molecular mechanisms involved in restoring the anatomical and functional integrity of the skin barrier.

The normal wound healing process follows four main stages beginning immediately after the wound and continuing until complete healing⁴:

The coagulation and hemostasis phase

• A clot composed of fibrin, fibronectin, vitronectin, Von Willebrand factor (VWF) and thrombospondin-5, forms immediately after the injury.
• The clot interrupts bleeding while recruiting inflammatory cells that will ensure wound healing.
• The fibrin clot also provides a matrix substrate on which cells involved in wound healing can subsequently grow and multiply: neutrophils, macrophages, endothelial cells and fibroblasts.

The inflammatory phase

The inflammatory phase can be subdivided into 2 phases:

Early inflammatory phase

It begins at the end of the coagulation phase:

• Complement activation.
• Infiltration of polymorphonuclear neutrophils (PMNs) (24-36 hours after the wound) to prevent bacterial infection and destroy foreign particles and damaged tissue.

Late inflammatory phase (48h to 72h after the wound)

• Recruitment of macrophages to the wound healing site with chemoattractants (complement components, cytokines, elastin and collagen breakdown products).
• Macrophages are an important reservoir of growth factors and other cellular mediators and lead to the activation of keratinocytes, fibroblasts and endothelial cells.
• Lymphocyte recruitment at the wound healing site 72h post-injury.

The proliferative phase

It begins when the immune response is established, about 3 days post-injury and up to about 2 weeks afterwards. It is marked by:

• Proliferation followed by migration of fibroblasts and myofibroblasts, and synthesis of a new extracellular matrix.
• Synthesis of collagen I and III by the fibroblasts. The fibers are oriented parallel to the cutaneous tension lines.
• Angiogenesis from existing vessels and synthesis of granulation tissue
• Wound contraction by myofibroblasts allowing the two edges of the wound to be brought together.

The remodelling phase

• It can last up to 1 to 2 years.
• It corresponds to the remodelling of the granulation tissue by the action of collagenases and by the apoptosis of residual cells, as well as the deployment of a mature scar tissue.
• At the end of this remodelling phase, the scar is devoid of vessels, shows a decrease in local metabolic activity and a partial but incomplete restoration of its tensile strength (elasticity).

Healing is complete when the skin and other tissues involved in the injury have returned to their original anatomical appearance, function and structure.

• This process takes 5 to 10 days and can take up to 30 days in a non-pathological situation (outside the remodelling phase).
• Depending on the severity of the wound and individual factors such as age, general health, treatment and medical history, the healing process can be altered and result in poor quality or pathological scars.

• The main abnormalities of acute wound healing are hypertrophic scars and keloid scars, each involving different molecular and cellular mechanisms.
• Both are nevertheless characterized by an excess of collagen production compared to normal skin: 7 times more collagen in hypertrophic scars, 20 times more in keloid scars⁶. 

Hypertrophic scars

• Erythematous, pruritic lesions that form a bulge and remain confined to the lesion site¹.
• Preferential areas of appearance: near joints or other stressed areas.
• Rapid development after the wound (4 to 12 weeks).
• Satisfactory evolution with progressive attenuation and flattening over time.

Keloid scars

• Keloid scars are more common in darker skinned individuals than in white skinned individuals.
• They protrude from the original wound site: scrapes, insect bites, vaccination shots, piercings, acne, surgical wounds or burns, usually in skin areas without hair follicles (neck, chest, shoulders, upper back, earlobes, abdomen).
• They can appear several years after the trauma and develop more slowly than hypertrophic scars.
• Unlike hypertrophic scars, keloids invade the surrounding skin and do not regress spontaneously.
• They frequently recur and can induce severe stress in the patient⁷.

Factors influencing wound healing

• The direction of the wound in relation to the skin tension lines (Langer lines): the orientation of the wound should be parallel to the Langer lines to achieve a good quality scar. Surgical wounds refer to these tension lines. Traumatic wounds perpendicular to these lines (especially at the level of a flexion fold) will systematically give a retractile scar. 
• Wound site:
  • Cursed areas: regardless of surgical technique, hypertrophic or keloid scars will usually be seen in the shoulder girdle, deltoid, pre-clavicular, and pre-sternal regions.
  • Thin-skinned areas (eyelids): heal quickly with an excellent result unlike thick skin in seborrheic regions that heal poorly.