From Wound to Scar: What Factors Are at Play in the Skin Healing Process?

In life, it’s inevitable to have some small accidents—like cutting yourself while chopping vegetables, falling off a bike, or popping a pimple… After the wound heals, many people wonder: why do some recover smoothly while others are left with noticeable marks?

To answer this question, we need to start from the moment the wound forms, delving into the deeper layers of the skin to explore the repair process involving fibroblasts, the extracellular matrix (ECM), and the inflammatory response.

Four Stages of Skin Repair: A Precise Relay
After skin injury, the stages of hemostasis, inflammation, repair, and remodeling unfold in sequence.
Step 1: Hemostasis – A few minutes after the injury, platelets gather and release signaling molecules that activate the clotting response, converting fibrinogen into fibrin to form a temporary “scaffold” that prevents blood loss and provides a landing point for subsequent cell migration.
Step 2: Inflammation – About 2 hours later, neutrophils and macrophages arrive to clear bacteria and debris, releasing signaling molecules. Inflammation needs to be moderate; excessive or prolonged inflammation can lead to more pronounced scarring.
Step 3: Repair – Fibroblasts are activated and differentiate into myofibroblasts, secreting large amounts of collagen (types I and III) and ECM proteins while also contracting the edges of the wound. New capillaries grow in, forming granulation tissue.
Step 4: Remodeling – This stage can last from several weeks to months. Myofibroblasts secrete enzymes to organize the collagen, degrading the excess while retaining the orderly arrangement, ultimately leading to cross-linking and stabilization. The appearance of the healed area is essentially determined at this stage.

Adult vs. Fetus: Why Do Fetal Healing Scars Appear Lighter?
When injured similarly, fetal skin heals with lighter scars, while adults are more likely to leave marks. Research reveals several key differences:
1. ECM Hardness
The extracellular matrix (ECM) in fetuses is softer than in adults, allowing fibroblasts to remain “calm” and be less prone to excessive activation. The harder ECM in adults makes cells more sensitive to mechanical stress, leading to increased collagen secretion, which may result in excessive deposition.
2. Different Ratios of TGF-β Subtypes
There are three subtypes of TGF-β (Transforming Growth Factor-β): TGF-β1 and TGF-β2 promote fibroblast activation and are involved in fibrosis; TGF-β3 tends to inhibit excessive activation and promotes healing that is closer to normal skin. Fetal wounds have higher expression of TGF-β3, while adults predominantly express TGF-β1 and TGF-β2. This difference in ratios affects the quality of healing.
3. Different Polarization States of Macrophages
Macrophages exist in two states: pro-inflammatory (M1) which release inflammatory factors, and anti-inflammatory/repair (M2) which release anti-inflammatory factors and participate in repair. Fetal wounds are primarily M2, while adults have a dominant M1 response initially, which lasts longer, continuously stimulating fibroblasts and potentially leading to excessive collagen deposition.

Molecular mechanisms of scar formation
Fibroblasts → Myofibroblasts
Myofibroblasts are key executors of scar formation, expressing α-SMA which provides contractile ability, and secreting a large amount of collagen. Upon activation, the stiffer ECM promotes further differentiation of fibroblasts, making the ECM even harder, creating a positive feedback loop.
Integrins – the “mechanical sensors” of cells
Integrins are transmembrane receptors on the surface of fibroblasts that convert physical signals from the ECM into intracellular signals. Different integrins have different functions: αvβ6 activates TGF-β to promote fibrosis, α5β1 maintains homeostasis, and α1β1 binds to type III collagen, corresponding to the phenomenon of scar-free healing in fetuses.

Collagen: An Important Component of Skin Structure
Collagen accounts for more than 75% of the dry weight of the skin. Type I collagen provides strength and is the main type found in adult skin; type III collagen is finer and softer, and is present in higher amounts in fetal and young tissues.
When the ratio of type III to type I is higher, the healed tissue is closer to the elasticity of normal tissue; when there is excessive deposition and disorganization of type I collagen, it is more prone to forming visible scars.

Scientific Skincare: General Principles Supporting the Skin’s Self-Repair
Based on the aforementioned mechanisms, daily care can refer to the following points:
1. Maintain appropriate hydration and softness of the skin—When the barrier is intact and adequately hydrated, the ECM environment is closer to a “soft” state, which is beneficial for fibroblast homeostasis.
2. Focus on collagen metabolism balance—The skin continuously synthesizes and degrades collagen. As mentioned earlier, the proportion of type III collagen has a direct impact on the quality of healing; thus, supplementing type III collagen in skincare helps provide more balanced collagen support for the skin.
3. Reduce excessive external stimuli—Factors such as ultraviolet rays, improper skincare, and mechanical friction may exacerbate local inflammation and affect the repair rhythm.
4. Choose gentle and reasonable skincare methods—Use products with mild formulations, avoid excessive exfoliation and aggressive squeezing, and allow the skin sufficient time for self-repair.
The skin is the largest organ of the human body and serves as our most direct barrier against the outside world. Each time a small wound heals, it is a “project” involving the precise cooperation of cells, matrix, and signaling molecules. Understanding this is not to induce anxiety, but to cultivate greater respect for the wisdom of the skin, promoting rational approaches in daily skincare. Scientific skincare is the greatest respect for the skin’s inherent powers.