DEFINITION OF A WOUND

1. BIOLOGY OF WOUND HEALING DEFINITION OF A WOUND • Loss of continuity of epithelial lining

2. BIOLOGY OF WOUND HEALING CLASSIFICATION OF WOUNDS • Incised • Laceration • Abrasion • Partial or Full Thickness • Acute or Chronic

3. BIOLOGY OF WOUND HEALING STAGES OF WOUND HEALING • Clot formation • Inflammatory Response • Re-epillielialization • Granulation Tissue Formation • Organisation/Remodelling • Wound Contraction

4. BIOLOGY OF WOUND HEALING CLOT FORMATION • Platelets plug  GFs and cytokine • Fibrin clot  temporary matrix

5. BIOLOGY OF WOUND HEALING KEY EVENTS IN INFLAMATION • Vasoactivity • Chemo-attraction • Complement activation • Coagulation activation • Collagen and other matrix digestion • Inflammatory cell accumulation & multiplication • Matrix deposition • Organisation or moulding

6. HUMORAL RESPONSE • Complement cascade • Coagulation cascade • Acute phase proteins

7. BIOLOGY OF WOUND HEALING PHAGOCYTIC CELL INVASION • Chemo attractants - compelement derived - platelet derived - leucocyte derived - other eg FDP • Neutrophils • Macrophages

8. BIOLOGY OF WOUND HEALING MACROPHAGES, MATRIX METALLOPROTEINASES AND THEIR TISSUE INHIBITORS • MØ’s secrete matric metalloproteinases (MMPS) which breakdown matrix and allow early cellular ingression. • MØ at wound site produce cytokines (TNF-, TGF- and IL-1) which upregulate TIMP-1 (Tissue inhibitor of MMPS) • TIMP-1 would protect matrix (basement mb and collagen) from continued degradation during healing process La Flear et al, J Exp Med 1996; 184: 2311-26

9. BIOLOGY OF WOUND HEALING RE-EPITHELIAZATION Proteases Matrix metalloprotease Leucocyte derived proteases tPA and uPA Other

10. BIOLOGY OF WOUND HEALING GRANULATION TISSUE • Fibroblasts • The matrix - collagen - glycans - other • Angiogenesis

11. BIOLOGY OF WOUND HEALING ROLE OF ADHESION MOLECULES • Matrix - fibronectin - vitronectin - thrombospondin - collagen - other • Cellular - selectins - integrin receptors - fibronectin receptors - vitronectin receptors

12. BIOLOGY OF WOUND HEALING MACROPHAGE STIMULATION INCREASE COLLAGEN BIOSYNTHESIS • Murine model of full thickness incision and colon anastomosis • Pre- and post-op treatment with glycan phosphate • Increased collagen synthesis measured by hydroxyproline • Increased tensile strength of both skin and colon repair Portera et al, Am Surgeon 1997; 63: 123-31

13. Chemotactic: PDGF C3a C5a TGF ß EGF IL-8 Mitogenic: PDGF EGF TGF  FGF VEGF CTGF IL-1  TNF BIOLOGY OF WOUND HEALING MELANGE OF GROWTH FACTORS AND CYTOKINE

14. BIOLOGY OF WOUND HEALING SELECTED GROWTH FACTORS IN WOUND HEALING - I Factor - PDGF Source - Platelet, Macroph, Fibrobl, Endoth, Sm Muscle Target - Neutrophils, Macroph, Fibrobl, Sm Muscle Function - Chemotaxis, Proliferation Collagen breakdown

15. BIOLOGY OF WOUND HEALING SELECTED GROWTH FACTORS IN WOUND HEALING - II • Factor - TGF • Source - Platelet, Keratino, Macroph • Target - Epith, Fibroblast, Endoth • Function - Proliferation

16. BIOLOGY OF WOUND HEALING SELECTED GROWTH FACTORS IN WOUND HEALING - III • Factor - IL-1 (endogenous pyrogen) • Source - Macroph • Target - Fibrobl, Neutrophils • Function - Proliferation, Collagen breakdown, Chemotaxis

17. BIOLOGY OF WOUND HEALING SELECTED GROWTH FACTORS IN WOUND HEALING - IV • Factor - TGF- • Source - Ubiquitous • Target - Ubiquitous • Function - Fibrosis Proliferation

18. BIOLOGY OF WOUND HEALING SELECTED GROWTH FACTORS IN WOUND HEALING-V • Factor - IGF-Isomatomedian C • Source - Fibrobl • Target - Fibrobl, Endoth • Function - Cell replication Collagen synth

19. BIOLOGY OF WOUND HEALING WOUND CONTRACTION • Organisation • Remodelling

20. BIOLOGY OF WOUND HEALING WOUND HEALING IN EMBRYO AND FOETUS • Regeneration • Non scarring healing • Role of neutrophils

21. BIOLOGY OF WOUND HEALING FOETAL WOUND REPAIR LACKS ACTIVATED MACROPHAGES AND B-CELLS • Murine foetal wound repair is scar free • There is delayed and fewer accumulation of MØ • Few Mac-1 positive cells noted • No B-cell detectable • No Neutrophilia Conin et al. Dev Dynamics 1998: 212: 385-393

22. BIOLOGY OF WOUND HEALING HYALURONIC ACID INDUCES MACROPHAGE PRODUCTION OF TNF-ALPHA IN VITRO • High foetal HA levels implicated for scarless repair • HA stimulated MØ secretion of TNF-alpha • TNF- is a potent inhibitor of fibroblast collegen synthesis

23. BIOLOGY OF WOUND HEALING DISORDERED WOUND HEALING • Poor wound healing • Hypertrophic scar and Keloid

24. BIOLOGY OF WOUND HEALING SYSTEMIC FACTORS THAT AFFECT WOUND HEALING General Malnutrition Specific - Micronutrient deficiencies - Vit A & C - Minerals eg Cu, Se Immunosuppression Diabetes Mellitus Collagen Disorders - Marfans - Collagen vascular dis Systemic Infection Obesity

25. BIOLOGY OF WOUND HEALING LOCAL FACTORS THAT AFFECT WOUND HEALING • Ischaemia - reduced arterial perfusion - venous stasis - smoking - radiation - oedema (compartment P°) - constant pressure • Infection - bacterial - fungal - parasitic • Foreign body

26. BIOLOGY OF WOUND HEALING PRINCIPLES OF SUTURING WOUND • Applicable to surgically clean wounds • Convert laceration to “surgical” wounds • Tension free apposition • Distribute tension evenly • across depth in layers • across length even spacing

27. BIOLOGY OF WOUND HEALING FUTURE PROSPECTS • Selective enhancement • Selective inhibition • Gene therapy