Overview
This lecture covers the stages of wound healing, focusing on the cellular and molecular events in a superficial skin wound.
Wound Healing Overview
- Wound healing speed varies by tissue; skin and intestines heal faster due to higher regenerative potential.
- Muscle and nerve tissues heal slowly or not at all because of low regenerative potential.
Stages of Wound Healing
- Four main stages: Hemostasis, Inflammation, Proliferation, and Remodeling.
Hemostasis
- Blood vessel damage causes bleeding; vasoconstriction limits blood loss.
- Platelets adhere to the injury site, attracting more cells to form a blood clot (platelet plug and fibrin mesh).
- Hemostasis prevents further external blood flow.
Inflammatory Reaction
- Pathogens may enter through the open wound; immune response is activated.
- Neutrophils arrive first, performing phagocytosis and recognizing pathogens via toll receptors.
- Macrophages follow and secrete cytokines (e.g., interleukin 1, 6), attracting more immune cells.
- Cytokines activate fibroblasts and endothelial cells, crucial for later repair steps.
- Macrophages secrete factors promoting angiogenesis (new blood vessel formation).
Growth Factors and Cell Types
- Platelets secrete TGF-beta and PDGF for angiogenesis and fibrosis.
- Keratinocytes, fibroblasts, macrophages, and mast cells release VEGF for blood vessel growth.
- Fibroblasts release FGF, assisting tissue remodeling.
- Metalloproteinases remodel the extracellular matrix (ECM).
Proliferation Phase
- Angiogenesis increases oxygen supply to the healing site.
- Fibroblasts proliferate, producing ECM components (collagen, fibronectin, proteoglycans).
- Nearby epithelial cells migrate to close the wound (reepithelialization).
- ECM begins remodeling at the end of proliferation.
Remodeling
- Metalloproteinases and their inhibitors reshape the ECM for proper wound closure.
- Proper ECM remodeling is essential for effective healing.
Types of Wound Closure
- Primary intention: wound edges are close together (e.g., sutures), resulting in a clean scar.
- Secondary intention: edges are far apart; healing occurs from bottom up, forming a larger scar.
Key Terms & Definitions
- Hemostasis — process to stop bleeding via blood clot formation.
- Phagocytosis — engulfing and destroying pathogens by immune cells.
- Angiogenesis — formation of new blood vessels.
- Cytokines — signaling proteins that regulate immune responses.
- ECM (Extracellular Matrix) — network of proteins and molecules supporting cell structure.
- Primary Intention — wound healing with closely approximated edges.
- Secondary Intention — healing with widely separated wound edges.
Action Items / Next Steps
- Review the roles of key growth factors (TGF-beta, PDGF, VEGF, FGF) in wound healing.
- Study examples of primary and secondary intention wound healing.