DEFINITION OF A WOUND Loss of continuity of epithelial lining BIOLOGY OF WOUND HEALING DEFINITION OF A WOUND Loss of continuity of epithelial lining

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

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

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

KEY EVENTS IN INFLAMATION 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

HUMORAL RESPONSE Complement cascade Coagulation cascade Acute phase proteins

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

MACROPHAGES, MATRIX METALLOPROTEINASES AND THEIR TISSUE INHIBITORS 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

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

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

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

MACROPHAGE STIMULATION INCREASE COLLAGEN BIOSYNTHESIS 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

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

SELECTED GROWTH FACTORS IN WOUND HEALING - I 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

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

SELECTED GROWTH FACTORS IN WOUND HEALING - III 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

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

SELECTED GROWTH FACTORS IN WOUND HEALING-V 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

BIOLOGY OF WOUND HEALING WOUND CONTRACTION Organisation Remodelling

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

FOETAL WOUND REPAIR LACKS ACTIVATED MACROPHAGES AND B-CELLS 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

HYALURONIC ACID INDUCES MACROPHAGE PRODUCTION OF TNF-ALPHA IN VITRO 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

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

SYSTEMIC FACTORS THAT AFFECT WOUND HEALING 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

LOCAL FACTORS THAT AFFECT WOUND HEALING 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

PRINCIPLES OF SUTURING WOUND 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

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