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

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

3. 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

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

5. 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

6. HUMORAL RESPONSE Complement cascade Coagulation cascade
Acute phase proteins

7. PHAGOCYTIC CELL INVASION
BIOLOGY OF WOUND HEALING
PHAGOCYTIC CELL INVASION
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
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:

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

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

11. 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

12. 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:

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. BIOLOGY OF WOUND HEALING
WOUND CONTRACTION
Organisation
Remodelling

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

21. 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:

22. 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

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

24. 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

25. 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

26. 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

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