Wound Healing & Scar Formation

Understanding how wounds heal is essential for preventing and treating hypertrophic and keloid scars. Wound healing occurs in three main phases—inflammation, transitional repair, and maturation—each of which plays a critical role in determining how much scar tissue forms.

Immediately following tissue injury, proteins released from the injured tissue and blood initiate the first stage of wound healing called the inflammation phase. The amount of blood released, extent of tissue damage, and bacteria content are the primary determinants of the intensity of inflammation. 

The main goal of this phase is to gain immunologic control of the wound. In general, wounds do not become sterile until it regains an epidermal cover. Thus, the length of time until wound closure is also important in determining the extent of wound inflammation.

The transitional repair phase begins a few days after injury and typically lasts for several weeks.

During this time, cell density increases around the wound as new blood vessels and epithelial tissue form to replace what was lost.

Cells are highly active and responsive to factors that regulate growth and matrix synthesis. Enzymes released into the extracellular space help both build and break down the temporary tissue matrix composed mainly of collagen and other proteins.

This delicate balance between degradation and biosynthesis determines how much new tissue, and ultimately how much scar, will form.

The maturation phase is the final phase of wound healing, and it begins in 6-12 weeks after wounding. When enough transitional matrix is produced, a turn-off signal is received, which initiates the maturation stage characterized by cellular apoptosis and a shift in balance of scar remodeling toward scar degradation. This process is accompanied by extracellular matrix reorganization and degradation. Tissue degrading enzymes released during the transitional repair phase continue to breakdown the extracellular matrix at a rate largely determined by physical and biochemical factors in the matrix. Additional extra-cellular matrix biosynthesis is controlled by the need for tissue strength and other operational parameters. Mechanical stress is an important deterministic parameter in the amount of scar production.

The most important factors influencing scar formation include:

• The magnitude and duration of inflammation

• The amount of mechanical tension acting on the healing wound

• The individual’s genetic and hormonal profile

The terminology around scarring can be confusing.

• Hypertrophic scars are raised, thickened scars that remain within the boundaries of the original wound.

• Keloid scars occur in individuals with keloid disease, where scars grow beyond the wound edges, forming tumor-like projections.

Factors that increase or prolong inflammation or wound tension predispose individuals to hypertrophic scarring.

Common causes include:

• Infection or delayed healing
• Foreign material in the wound
• Burn wounds that take longer than 21 days to close

The incidence of hypertrophic scarring is 40–70% after surgery and up to 91% following burns.

Scars in areas of high skin tension, such as the sternum, shoulders, and upper back, are especially prone to becoming hypertrophic. While no hereditary pattern has been clearly established, populations with higher skin melanin content, including African, Asian, and Hispanic individuals, have a higher incidence of hypertrophic scars. Hormonal changes may also influence scar formation, with hypertrophic scars often appearing at puberty or during pregnancy. Over time, most hypertrophic scars regress naturally, leaving behind a thinned dermal gap that may remain visible.