Wound Healing: Phases, Primary and Secondary Intention, Complications and Clinical Factors

Learning outcomes

• Describe the phases of wound healing and their major cells, mediators and matrix changes.
• Explain healing by primary, secondary and tertiary intention.
• Distinguish regeneration from scar formation and understand wound contraction.
• Recognise normal versus delayed or excessive healing.
• Identify local and systemic factors that impair repair.
• Apply wound-healing principles to emergency wound assessment and aftercare.

1. Regeneration versus repair

Process	Outcome	Determinants
Regeneration	Replacement by cells of the same type with near-normal function.	Intact extracellular matrix, viable stem/progenitor cells and limited tissue loss.
Repair by scar	Collagen and matrix replace lost tissue; strength improves but function may not fully return.	Large defect, damaged matrix, non-regenerating tissue or persistent inflammation.
Mixed healing	Some areas regenerate while others scar.	Most real wounds, infarcts and chronic ulcers.

2. Phase 1: Haemostasis

Haemostasis begins immediately after injury.

1. Vasoconstriction: limits blood loss.
2. Platelet adhesion: von Willebrand factor bridges platelets to exposed collagen.
3. Platelet activation: ADP, thromboxane A₂ and serotonin recruit more platelets.
4. Coagulation: thrombin converts fibrinogen to fibrin, stabilising the plug.
5. Provisional matrix: fibrin, fibronectin and platelet proteins provide a scaffold for migrating cells.

Platelets release PDGF, TGF-β, VEGF and EGF, linking clotting to inflammation and repair.

3. Phase 2: Inflammation

Neutrophils arrive early to remove bacteria and debris. Macrophages then clear apoptotic neutrophils and necrotic material and coordinate the transition to repair.

• Histamine and prostaglandins increase flow and permeability.
• Neutrophil ROS/proteases kill organisms but can injure tissue.
• Macrophage IL-1/TNF recruit cells; later IL-10/TGF-β support resolution.
• Persistent contamination or necrosis prolongs inflammation and delays closure.

4. Phase 3: Proliferation

4.1 Re-epithelialisation

Basal keratinocytes loosen attachments, migrate across the wound and proliferate behind the leading edge. Growth factors from platelets, macrophages and keratinocytes coordinate the process. Moist, protected wound surfaces support epithelial migration.

4.2 Angiogenesis

Hypoxia stabilises HIF-1α, which increases VEGF. Endothelial cells degrade basement membrane, migrate, proliferate and form capillary loops. New vessels make granulation tissue red and bleed easily.

4.3 Fibroblast migration and collagen deposition

PDGF, TGF-β and FGF recruit fibroblasts. Early collagen is mainly type III; fibronectin and proteoglycans provide a provisional matrix. Myofibroblasts express alpha-smooth-muscle actin and contract the wound.

4.4 Granulation tissue

Granulation tissue contains new capillaries, fibroblasts, macrophages, loose extracellular matrix and type III collagen. It fills defects and supports epithelium; healthy granulation is moist, red and granular.

5. Phase 4: Remodelling and maturation

Over weeks to months, collagen III is replaced by stronger collagen I. Matrix metalloproteinases degrade old matrix while tissue inhibitors restrain them. Collagen fibres align along lines of tension and cross-link.

Time	Typical event
Days	Fibrin matrix, neutrophils and early macrophages.
1–3 weeks	Granulation tissue, angiogenesis, fibroblasts and type III collagen.
Weeks–months	Collagen I maturation, reduced vascularity and increasing tensile strength.
Months+	Scar becomes paler and flatter; strength plateaus below uninjured tissue.

Scar strength rises rapidly early but generally reaches only about 70–80% of original tissue strength; it never regains the exact normal architecture.

6. Healing by primary intention

Primary intention occurs when wound edges are closely apposed, as in a clean sutured incision.

• Small clot and limited necrosis.
• Minimal inflammation and granulation tissue.
• Rapid epithelial bridging.
• Thin scar with little contraction.
• Lower infection risk if contamination is controlled.

Accurate alignment, gentle tissue handling, haemostasis and early closure favour primary healing.

7. Healing by secondary intention

Secondary intention occurs when there is a large tissue defect, tissue necrosis, contamination or wound edges cannot be approximated.

• More inflammation and granulation tissue.
• Greater collagen deposition and wound contraction.
• Slower epithelialisation and a larger scar.
• Higher risk of infection, hypertrophic scar and contracture.

Examples include pressure ulcers, large abscess cavities and wounds left open after debridement.

8. Healing by tertiary intention (delayed primary closure)

Tertiary intention leaves a contaminated or infected wound open initially for drainage, observation and debridement. Once bacterial burden and oedema decrease, the wound is closed. It combines the safety of delayed source control with the cosmetic and functional advantages of primary closure.

9. Wound contraction

Myofibroblasts attach to collagen and pull wound edges together. Contraction reduces the surface area but can distort joints, eyelids, mouth, fingers or the neck. Excessive contraction after burns causes contractures and functional limitation.

10. Factors that affect healing

Factor	Effect on healing	Clinical action
Infection	Prolongs inflammation, destroys matrix and increases dehiscence.	Clean, culture when indicated, drain/debride and use appropriate antimicrobials.
Ischaemia/hypoxia	Impairs collagen synthesis, angiogenesis and leukocyte killing.	Restore perfusion, stop smoking and optimise oxygenation.
Foreign bodies	Maintain inflammation and sinus formation.	Remove when safe; image retained material.
Diabetes	Microvascular disease, neuropathy, glycation and immune dysfunction.	Glucose control, foot care and vascular assessment.
Malnutrition	Protein, vitamin C, zinc and iron deficiency impair matrix and immunity.	Nutrition assessment and protein/micronutrient replacement.
Glucocorticoids	Suppress inflammation, fibroblasts and collagen.	Balance indication; do not stop essential steroids abruptly.
Mechanical stress	Shear, tension and pressure disrupt fragile repair.	Immobilise, offload, support and close appropriately.
Ageing	Reduced angiogenesis, stem-cell reserve and collagen response.	Prevent pressure injury, optimise nutrition and mobilise safely.

11. Complications

Complication	Mechanism/feature
Wound dehiscence	Separation from infection, poor collagen, tension or malnutrition; emergency if bowel protrudes.
Incisional hernia	Weak scar permits abdominal contents to bulge.
Hypertrophic scar	Excess collagen remains within wound boundaries and may regress.
Keloid	Excess collagen extends beyond wound margins; recurrence is common.
Contracture	Excessive contraction limits movement, especially after burns.
Chronic ulcer	Persistent pressure, ischaemia, neuropathy, infection or systemic disease prevents closure.
Exuberant granulation	“Proud flesh” rises above the wound edge and blocks epithelial migration.

12. Emergency wound assessment

1. Control life-threatening bleeding with direct pressure, haemostatic measures and escalation when needed.
2. Assess airway, breathing and circulation in major burns, trauma or facial injury.
3. Evaluate perfusion and function: pulses, capillary refill, sensation, movement and tendon/nerve injury.
4. Identify contamination and foreign bodies and assess tetanus risk.
5. Look for deep infection/necrosis: pain out of proportion, rapid spread, bullae, crepitus, systemic toxicity.
6. Choose closure timing: clean wounds may close primarily; contaminated wounds may need delayed closure.
7. Provide follow-up: dressing, offloading, glucose/nutrition optimisation, rehabilitation and review for infection.

13. Applied cases

Case 1: Clean laceration

After haemostasis, irrigation and assessment of nerves/tendons, closely approximate the edges for primary intention if contamination and tissue viability allow. Tension-free closure and follow-up reduce dehiscence and infection.

Case 2: Contaminated crush wound

Devitalised tissue and contamination maintain inflammation. Debridement, perfusion assessment, tetanus prevention and delayed closure may be safer than immediate suturing.

Case 3: Diabetic foot ulcer

Neuropathy, pressure, ischaemia and infection interfere with all phases of healing. Offload the foot, assess pulses and infection depth, optimise glucose/nutrition and coordinate multidisciplinary care.

14. Quick self-test

1. What are the four broad phases of wound healing?
   Answer: Haemostasis, inflammation, proliferation and remodelling/maturation.
2. Which cells initiate repair after neutrophils?
   Answer: Macrophages, followed by fibroblasts and endothelial cells.
3. What is healing by primary intention?
   Answer: Closure of a clean, closely apposed wound with minimal tissue loss and scar.
4. When is secondary intention used?
   Answer: Large, contaminated, infected or tissue-deficient wounds that cannot be safely approximated.
5. What is tertiary intention?
   Answer: Delayed primary closure after contamination, oedema or infection has been controlled.
6. Name three factors that delay healing.
   Answer: Infection, ischaemia, diabetes, malnutrition, steroids, foreign bodies, age or mechanical stress.
7. Why can an apparently closed wound reopen?
   Answer: Scar strength is initially low and infection, tension, poor collagen or systemic disease can cause dehiscence.

15. Take-home summary

Selected references

• NCBI Bookshelf: Wound Healing
• NCBI Bookshelf: Wound Closure Techniques
• NCBI Bookshelf: Inflammation and Repair

Educational note: This resource supports learning and clinical reasoning. Current local protocols, senior supervision and national guidelines take precedence in patient care.