Wound Healing Phases and Factors

Overview

This lecture covers the four key phases of wound healing, the main cells and processes involved, and factors influencing normal and impaired healing.

Wound healing occurs in four overlapping phases: hemostasis, inflammation, proliferation, and remodeling.
Each phase is defined by distinct cellular activities and biochemical changes.

Begins immediately after injury with blood vessel constriction and platelet plug formation.
Platelets and clotting factors create a fibrin mesh to stop bleeding and support cell migration.
Platelets release growth factors (PDGF, TGF-β, PAF, fibronectin) and serotonin to promote repair.
Injured tissues release prostaglandins and cytokines to trigger the inflammatory response.

Initiated by increased adhesion molecules, cytokines, vasodilation, and vascular permeability.
Neutrophils arrive first (24–48 hours) to remove bacteria and debris via phagocytosis.
Macrophages peak at 72 hours, are essential for phagocytosis, recruiting cells, angiogenesis, and matrix synthesis.

Oxygenated blood is provided to the wound via new blood vessel formation (angiogenesis).
Key cells: fibroblasts, endothelial cells, keratinocytes (in skin).
Three major processes: angiogenesis (new vessels), granulation (matrix formation by fibroblasts), and reepithelialization (keratinocytes reform barrier).

Fibroblasts transform to myofibroblasts and remodel the extracellular matrix, forming scar tissue.
Myofibroblasts contract the wound and eventually undergo apoptosis.
Scar tissue matures over 6–12 months, becoming avascular and acellular.

Local factors: wound type, size, location, pressure, edema, hydration, blood supply, infection, foreign bodies.
Systemic factors: age, medications (steroids, antibiotics), comorbidities (diabetes, heart failure, obesity), and nutritional deficiencies (especially vitamin C).

Primary intention: wound edges are brought together (sutured), heals quickly with minimal tissue loss (e.g., surgical wounds).
Secondary intention: wound edges not opposed, healing occurs from the bottom up with granulation and reepithelialization (e.g., burns, trauma).

Hemostasis — initial stopping of bleeding via blood clot formation.
Phagocytosis — process where cells (neutrophils, macrophages) engulf and digest debris and microbes.
Angiogenesis — formation of new blood vessels.
Granulation tissue — new connective tissue and microscopic blood vessels in the wound.
Reepithelialization — restoration of epithelial (skin) layer.
Myofibroblast — specialized fibroblast with contractile abilities aiding wound closure.