Phases of Wound Healing

Wound healing occurs in three overlapping phases:
→ Inflammation → Proliferation → Maturation (Remodeling)
(Hemostasis is sometimes considered a separate, initial step.)

1. Inflammation Phase (Days 0–6)

🩸 Haemostasis (Immediate)

• Vasoconstriction (↓ blood flow): thromboxane A2, prostaglandins

• Platelet plug formation & clotting cascade → Fibrin clot → matrix for healing

🔥 Inflammatory Response

• Vasodilation → classic signs: redness, heat, swelling, pain

• Neutrophils (Day 1): phagocytose bacteria, release ROS

• Macrophages (Day 2–3):

  • Clear debris

  • Release cytokines

  • Recruit fibroblasts, keratinocytes, endothelial cells

• Lymphocytes (Late phase): immune regulation

2. Proliferation Phase (Days 4–30)

🔧 Rebuilding the Wound

• Granulation Tissue Formation

  • Fibroblasts + capillaries + ECM = red/pink, healing wound bed

• Angiogenesis

  • Triggered by hypoxia

  • New vessels supply O₂ & nutrients

• Fibroblasts → Collagen Synthesis

  • Type III collagen initially

  • ECM formation (glycosaminoglycans, proteoglycans)

  • Nutrients: Vitamin C, protein

• Myofibroblasts → Wound Contraction

• Epithelialization

  • Keratinocytes migrate to cover wound

  • Enhanced by moist wound environment

3. Maturation Phase (Remodelling) (Starts ~Day 21 → Months/Years)

🎯 Goal: Restore strength & function

• Collagen Remodelling

  • Replace Type III → Type I collagen

  • ↑ Cross-linking = ↑ tensile strength (~80%)

• Angiogenesis Regression

  • Vessels fade → scar becomes less vascular

• Cellular Apoptosis

  • ↓ Fibroblasts, ↓ metabolic activity

• Scar Formation

Factors Affecting Wound Healing

A. 🧓 Age

• Delayed healing in older adults

• ↓ Inflammatory response

• Skin = thinner, more fragile

• ↓ Estrogen in postmenopausal women = slower healing

• ↑ Comorbidities (diabetes, malnutrition, dehydration)

B. 🩺 Comorbidities

Diabetes Mellitus

• Chronic hypoxia

• Prolonged inflammation

• ↑ Proteases (MMPs) → degrade healing tissue

• ↓ Neovascularisation (↓ VEGF, EPCs)

• Neuropathy → ↓ neuropeptide release

• ↑ Infection risk

Cardiovascular Disease

• ↓ Perfusion (PAD, CAD, venous insufficiency)

Immunodeficiency (e.g., HIV, cancer)

• ↓ Immune surveillance

• ↑ Risk of infection

Obesity

• ↓ Vascularity of fat

• ↑ Wound tension = dehiscence

• ↑ Risk of infection and pressure ulcers

• Adipokines → pro-inflammatory, impair repair

C. 💊 Medications

D. 🦠 Infection

• Delays healing at all stages

• ↑ Pro-inflammatory cytokines → prolonged inflammation

• ↑ MMPs → ECM breakdown

• Biofilms (e.g., S. aureus, P. aeruginosa) create barriers and resist antibiotics

• Tissue damage + bacterial toxins impair proliferation

Summary Table

Understanding these phases and their influencing factors is essential in both clinical wound care and dermatological conditions involving delayed healing (e.g., chronic ulcers, diabetic foot wounds).
👉 Addressing modifiable risk factors can significantly enhance healing outcomes.

References

1. Wound Evolution. (n.d.). The Four Stages of Wound Healing. Retrieved from https://www.woundevolution.com/blog/the-four-stages-of-wound-healing/

2. Guo, S., & Dipietro, L. A. (2010). Factors affecting wound healing. Journal of Dental Research, 89(3), 219–229. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK470443/

3. Sorg, H., Tilkorn, D. J., Hager, S., Hauser, J., & Mirastschijski, U. (2017). Skin wound healing: An update on the current knowledge and concepts. European Surgical Research, 58(1–2), 81–94. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK534261/

4. Elastoplast. (n.d.). Stages of Wound Healing. Retrieved from https://www.elastoplast.co.uk/did-you-know/health-and-protection/stages-of-wound-healing

5. Guo, S., & DiPietro, L. A. (2010). Factors affecting wound healing. Journal of Dental Research, 89(3), 219–229. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC2903966/

6. Dowsett, C., & Newton, H. (2011). Checklist for factors affecting wound healing. Advances in Skin & Wound Care, 24(4), 192–194. Retrieved from https://journals.lww.com/aswcjournal/fulltext/2011/04000/checklist_for_factors_affecting_wound_healing.10.aspx

7. Manna, B., Nahirniak, P., & Morrison, C. A. (2022). Wound Healing Overview. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK482254/

8. Wound Care Inc. (n.d.). Factors That Affect Wound Healing. Retrieved from https://www.woundcareinc.com/resources/factors-that-affect-wound-healing