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1. Wound Healing Behrooz A. Torkian MD
2. Introduction Basis of repair of tissues
Enables surgical treatment
May take advantage for our benefit
Complications
Modification and Enhancement
3. Phases of Wound Healing
4. Vascular Initial vasoconstriction (5-10 min) then vasodilation (persistent)
Exposure of subendothelial von Willebrand / factor VII, and fibrillar collagen platelet plug
Hageman factor (XII) initiation of clotting cascade and fibrin clot formation
5. Clotting Cascade
6. Inflammatory Platelets
derived growth factor (PDGF), proteases and vasoactive substances such as serotonin and histamine
Polymorphonuclear leukocytes
Macrophages (replace PMNs after 5 days)
Fibroblasts (recruited by chemotactic factors released by the above cells)
7. Reepithelization Migration (wound edges, hair follicles, adnexa)
Proliferation (48-72 hours)
Sutured wounds have a layer of keratinocytes within 24-48 hours
8. Keratinocytes Fibronectin
Cross links to fibrin matrix/scaffold for keratinocyte adhesion and migration
Functions as an early component of the extracellular matrix.
Binds to collagen and interacts with matrix glycosaminoglycans.
Has chemotactic properties for macrophages, fibroblasts and endothelial and epidermal cells.
Promotes opsonization and phagocytosis.
Forms a component of the fibronexus.
Forms scaffolding for collagen deposition
Collagenases and neutral proteases debridement
Plasminogen activator clot dissolution
Type V collagen
Requires moisture for epithelial migration
9. Granulation Highly vascular network of glycoproteins, collagen and glycosaminoglycans
Fibroblasts
collagen
Elastin
Fibronectin
Sulfated and non-sulfated Glycosaminoglycans
Proteases
Inflammatory cells
10. Fibroplasia Fibroblasts
Mainly Type III collagen first
Replaced by type I and II collagen
Hydroxylation of proline and lysine
Iron, copper, vitamin C
Crosslinkage
11. Contraction Myofibroblasts
Fibronexus (Singer)
Connections between intracellular actin microfilaments and extracellular collagen, fibronectin, and between myofibroblasts
Transmits force along entire network
Centripetal contraction
12. Neovascularization Fibronectin
Macrophage derived angiogenic factor
Endothelial migration
13. Wound Remodeling Increased tensile strength
Decreased bulk, and erythema
Replacement of fibronectin by collagen
Dehydration
Promotes further crosslinkage of collagen
Reorientation of collagen to parallel skin collagen.
16. Local Factors Infection
Technique (wound edge ischemia)
Hematoma
Foreign body reaction
Tissue ischemia
Topical medications and dressings
17. Systemic Factors Deficiency states
Insulin
Protein (nitrogen balance)
Vitamins
A slower re-epithelization
C Collagen
K clot formation
Trace minerals and elements
Zinc, copper, iron, manganese
18. Systemic Factors Medications
Glucocorticoids
Anticoagulants
Antineoplastic drugs
Cyclosporin A
Colchicine
Penicillamine
Zinc sulfate (high doses)
Beta amino proprionitrile
19. Growth Factors Epidermal growth factor
Macrophage derived growth factor (MDGF)
Platelet derived growth factor (PDGF)
Thrombin
Insulin
Lymphokines
21. Plasminogen activator inhibitor -1 Found to be elevated in Keloid scars
PAI-1 -/- knockout mice show accelerated wound healing after cutaneous injury
PAI-1 seems to regulate fibrinolytic and proteolytic activity during the replacement of fibrin by collagen.
PAI-1 is upregulated in cultured fibroblasts in a hypoxic environment
22. Metalloproteinases & Tissue Inhibitor of Metalloproteinases Regulatory role in fibroblasia and scarring
Found in high concentrations in fetal wounds
MMP/TIMP is higher in scarless fetal wounds
TGF-beta decreased the MMP/TIMP ratio by increasing TIMP
May promote more rapid epithelization
23. TGF Beta-1 Higher concentrations and exaggerated response in keloid fibroblasts
When added to fetal wounds thicker scars made.
25. Silicone Decreases TGF-Beta-2, and contraction of RAFT-fibroblast cultures (Kuhn et. al.)
Increased bFGF levels in cultured fibroblasts (HanasonoKoch)
Anecdotal evidence
26. References Silvia Wagner, PhD et. al. Comparison of inflammatory and systemic sources of growth factors in acute and chronic human wounds, Wound Repair and Regeneration Volume 11Issue 4Page 253 - July 2003 doi:10.1046/j.1524-475X.2003.11404.x
Deodhar AK, Rana RE. Surgical physiology of wound healing: a review. J Postgrad Med [serial online] 1997 43:52-6 http://www.jpgmonline.com/article.asp?issn=0022-3859;year=1997;volume=43;issue=2;spage=52;epage=6;aulast=Deodhar
Ziv PM et. al., Matrix Metalloproteinases and the ontogeny of scarless repair: the other side of the wound healing balance, Plastic and Reconstructive Surgery 110(3):801-11 2002
Bullard KM et. al. Fetal wound healing: Current Biology, World J. Surg 27: 54-61, 2003
Singer AJ, Clark RAF, Cutaneous Wound Healing, NEJM 341(10) 738-46; 2001
Saulis AS, Mogford JH, Mustoe TA.Related Articles, Links Effect of Mederma on hypertrophic scarring in the rabbit ear model.Plast Reconstr Surg. 2002 Jul;110(1):177-83; discussion 184-6.
Hanasono MM, Lum J, Carroll LA, Mikulec AA, Koch RJ.Related Articles, Links The effect of silicone gel on basic fibroblast growth factor levels in fibroblast cell culture.Arch Facial Plast Surg. 2004 Mar-Apr;6(2):88-93.