DEFINITION OF A WOUND

1
DEFINITION OF A WOUND
BIOLOGY OF WOUND HEALING

• Loss of continuity of epithelial lining

2
CLASSIFICATION OF WOUNDS
BIOLOGY OF WOUND HEALING

• Incised
• Laceration
• Abrasion
• Partial or Full Thickness
• Acute or Chronic

3
STAGES OF WOUND HEALING
BIOLOGY OF WOUND HEALING

• Clot formation
• Inflammatory Response
• Re-epillielialization
• Granulation Tissue Formation
• Organisation/Remodelling
• Wound Contraction

4
CLOT FORMATION
BIOLOGY OF WOUND HEALING

• Platelets plug ? GFs and cytokine
• Fibrin clot ? temporary matrix

5
KEY EVENTS IN INFLAMATION
BIOLOGY OF WOUND HEALING

• 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
PHAGOCYTIC CELL INVASION
BIOLOGY OF WOUND HEALING

• Chemo attractants
• - compelement derived
• - platelet derived
• - leucocyte derived
• - other eg FDP
• Neutrophils
• Macrophages

8
MACROPHAGES, MATRIX METALLOPROTEINASES AND THEIR
TISSUE INHIBITORS
BIOLOGY OF WOUND HEALING

• MØs 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
RE-EPITHELIAZATION
BIOLOGY OF WOUND HEALING

• Proteases
• Matrix metalloprotease
• Leucocyte derived proteases
• tPA and uPA
• Other

10
GRANULATION TISSUE
BIOLOGY OF WOUND HEALING

• Fibroblasts
• The matrix - collagen
• - glycans
• - other
• Angiogenesis

11
ROLE OF ADHESION MOLECULES
BIOLOGY OF WOUND HEALING

• Matrix - fibronectin
• - vitronectin
• - thrombospondin
• - collagen
• - other
• Cellular - selectins
• - integrin receptors
• - fibronectin receptors
• - vitronectin receptors

12
MACROPHAGE STIMULATION INCREASE COLLAGEN
BIOSYNTHESIS
BIOLOGY OF WOUND HEALING

• 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
MELANGE OF GROWTH FACTORS AND CYTOKINE
BIOLOGY OF WOUND HEALING

• Chemotactic
• PDGF
• C3a
• C5a
• TGF ?ß
• EGF
• IL-8

• Mitogenic
• PDGF
• EGF
• TGF ??
• FGF
• VEGF
• CTGF
• IL-1 ??
• TNF?

14
SELECTED GROWTH FACTORS IN WOUND HEALING - I
BIOLOGY OF WOUND HEALING

• Factor - PDGF
• Source - Platelet, Macroph, Fibrobl, Endoth,
  Sm Muscle
• Target - Neutrophils, Macroph, Fibrobl, Sm
  Muscle
• Function - Chemotaxis, Proliferation
• Collagen breakdown

15
SELECTED GROWTH FACTORS IN WOUND HEALING - II
BIOLOGY OF WOUND HEALING

• Factor - TGF?
• Source - Platelet, Keratino, Macroph
• Target - Epith, Fibroblast, Endoth
• Function - Proliferation

16
SELECTED GROWTH FACTORS IN WOUND HEALING - III
BIOLOGY OF WOUND HEALING

• Factor - IL-1 (endogenous pyrogen)
• Source - Macroph
• Target - Fibrobl, Neutrophils
• Function - Proliferation, Collagen
  breakdown, Chemotaxis

17
SELECTED GROWTH FACTORS IN WOUND HEALING - IV
BIOLOGY OF WOUND HEALING

• Factor - TGF-?
• Source - Ubiquitous
• Target - Ubiquitous
• Function - Fibrosis
• Proliferation

18
SELECTED GROWTH FACTORS IN WOUND HEALING-V
BIOLOGY OF WOUND HEALING

• Factor - IGF-Isomatomedian C
• Source - Fibrobl
• Target - Fibrobl, Endoth
• Function - Cell replication
• Collagen synth

19
WOUND CONTRACTION
BIOLOGY OF WOUND HEALING

• Organisation
• Remodelling

20
WOUND HEALING IN EMBRYO AND FOETUS
BIOLOGY OF WOUND HEALING

• Regeneration
• Non scarring healing
• Role of neutrophils

21
FOETAL WOUND REPAIR LACKS ACTIVATED MACROPHAGES
AND B-CELLS
BIOLOGY OF WOUND HEALING

• 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
HYALURONIC ACID INDUCES MACROPHAGE PRODUCTION OF
TNF-ALPHA IN VITRO
BIOLOGY OF WOUND HEALING

• 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
DISORDERED WOUND HEALING
BIOLOGY OF WOUND HEALING

• Poor wound healing
• Hypertrophic scar and Keloid

24
SYSTEMIC FACTORS THAT AFFECT WOUND HEALING
BIOLOGY OF 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
LOCAL FACTORS THAT AFFECT WOUND HEALING
BIOLOGY OF WOUND HEALING

• Ischaemia - reduced arterial perfusion
• - venous stasis
• - smoking
• - radiation
• - oedema (compartment P)
• - constant pressure
• Infection - bacterial
• - fungal
• - parasitic
• Foreign body

26
PRINCIPLES OF SUTURING WOUND
BIOLOGY OF WOUND HEALING

• 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
FUTURE PROSPECTS
BIOLOGY OF WOUND HEALING

• Selective enhancement
• Selective inhibition
• Gene therapy