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Wound Healing Wound Healing • Dhaval Bhavsar, MD • Assistant Professor Dept of Plastic, Wound and Burn Surgery KUMC Dhaval Bhavsar, Wound Healing (Basics) Skin • Largest Organ • Provides . Protection from elements, Infective organisms . Protective sensation • When breached – infection, loss of thermal regulation Dhaval Bhavsar, Wound Healing (Basics) Normal Skin http://www.agen.ufl.edu/~chyn/age2062/lect/lect_19/174.gif Dhaval Bhavsar, Wound Healing (Basics) Epidermis http://www.ratbehavior.org/images/Epidermis.jpg Dhaval Bhavsar, Wound Healing (Basics) Dermis http://neuromedia.neurobio.ucla.edu/campbell/skin/wp_images/161_dermis.gif Dhaval Bhavsar, Wound Healing (Basics) What is Wound “any break in the skin or an organ caused by violence or surgical incision” http://www.udap.com/images/yellowstone Dhaval Bhavsar, Wound Healing (Basics) Wound Healing • restoration of continuity after wounding http://fulton.edzone.net/cites/winkler-science/team1/chapter%205/image11.gif Dhaval Bhavsar, Wound Healing (Basics) Wound Healing- 3 Classic Phases • Inflammation • Proliferation • Remodeling http://www.bumc.bu.edu/www/Busm/sg/Images/suturing/phase2.gif Dhaval Bhavsar, Wound Healing (Basics) Hemostasis • Clot formation • Start point of inflammation Dhaval Bhavsar, Wound Healing (Basics) Inflammatory phase • Starts within 6-8 hrs • PMN cells • Later Monocytes (Macrophages) Dhaval Bhavsar, Wound Healing (Basics) Inflammation • Reaches its height at 24-48 hrs • Also release growth factors • Prepares wound for proliferation Dhaval Bhavsar, Wound Healing (Basics) Proliferation • Fibroplasia • Matrix deposition • Angiogenesis • Re-epithelialization Dhaval Bhavsar, Wound Healing (Basics) Granulation tissue http://www.worldwidewounds.com/2002/april/Vowden/images/WBP-Figure-5e.jpg http://medweb.bham.ac.uk/http/depts/path/Teaching Dhaval Bhavsar, Wound Healing (Basics) Fibroplasia • Fibroblasts – activated fibrocytes • Most important cells • Secrete- •Collagen •Glycosaminoglycans •Elastin •Fibronectin •Protease Dhaval Bhavsar, Wound Healing (Basics) Fibroplasia • Fibroblasts increase in number as inflammatory cells decrease • Begins 3-5 days after wounding • Migrate and proliferate in response to fibronectin, platelet-derived growth factor (PDGF), fibroblast growth factor, transforming growth factor, and C5a Dhaval Bhavsar, Wound Healing (Basics) Collagen deposition • The most important matrix component • Deposition starts about 3rd day and continues for 2-4 weeks depending on wound size • Procollagen Tropocollagen Collagen Dhaval Bhavsar, Wound Healing (Basics) Collagen Deposition • Collagen deposition dependent on • Age • Tension • Pressure • Stress Dhaval Bhavsar, Wound Healing (Basics) Matrix • Source- fibroblasts • Components . GAG . Heparin Sulfate . Chondroitin Sulfate . Hyaluronic Acid . Dermatan Sulfate Dhaval Bhavsar, Wound Healing (Basics) Angiogenesis • Wound healing requires rich blood supply to sustain newly formed tissue • It is evident in erythema (redness) of the new scar • Capillary density decreases as the need reduces and scar matures Dhaval Bhavsar, Wound Healing (Basics) Angiogenesis • Macrophages release- Macrophage derived angiogenic factor in response to low tissue oxygen tension • Work as chemoattractant • Basic FGF and VEGF are also important Dhaval Bhavsar, Wound Healing (Basics) Angiogenesis • Endothelial cells bud arise from capillary ends • Produced in line http://www.med.unibs.it/~airc/angio2.gif • Endothelial cells coalesce and bind fibrin Dhaval Bhavsar, Wound Healing (Basics) Re-epithelialization • Covers the granulation tissue with epidermal cells and completes wound healing • Re-establishes the barrier Dhaval Bhavsar, Wound Healing (Basics) Re-epithelialization • Actin-rich protrusions, lamellipodia and filopodia • Adhesions at the leading edge • Cells move forward by contracting the actin cytoskeleton • Coordinated processes of http://www.biochemweb.org/fenteany/research/cell_migration/ adhesion assembly, disassembly and turnover Dhaval Bhavsar, Wound Healing (Basics) Epithelial Cell Migration http://www.biochemweb.org/fenteany/research/cell_migration/ Dhaval Bhavsar, Wound Healing (Basics) Wound Contraction • Centripetal movement of wound edges • Maximal rate of contraction - 0.75 mm/day • Depends on the degree of tissue laxity and shape of the wound • Role of myofibroblast Dhaval Bhavsar, Wound Healing (Basics) Myofibroblast http://www.grad.ucl.ac.uk/comp/2003/research/gallery/entries/large/016.jpg Lab Invest 2003, 83:1689-1707 Dhaval Bhavsar, Wound Healing (Basics) Remodeling • Collagen remodeling – depends on balance between new collagen formation and collagen destruction • Collagenase and Matrix metalloproteinase Dhaval Bhavsar, Wound Healing (Basics) Remodeling • Collagen becomes increasingly organized • Fibronectin gradually disappears • Hyaluronic acid and glycosaminoglycans are replaced by proteoglycans • Water is resorbed • These events allow collagen fibers to lie closer together, facilitating collagen cross-linking Dhaval Bhavsar, Wound Healing (Basics) Remodeling • Begins approximately 21 days after injury • Remodeling may continue indefinitely Dhaval Bhavsar, Wound Healing (Basics) Strength of Repaired Wound • Tensile strength- load capacity per unit area • Maximum achieved in 90 days • Usually it is 80% of original strength • Bursting strength- force required to break a wound regardless of its dimension Dhaval Bhavsar, Wound Healing (Basics) Clinical Wound Healing http://www.anat.ucl.ac.uk/business/images/woundhealing.jpg • Stages are concurrent • Epithelial migration – 1mm/day • Requires intervention if larger than 5 cm Dhaval Bhavsar, Wound Healing (Basics) Burn Wound Healing Superficial Partial • Superficial- primary Deep epithelization • Partial- From epithelial appendages • Deep partial- slow epithelization from remaining epithelial appendages • Deep- Can not epithelize Dhaval Bhavsar, Wound Healing (Basics) Dhaval Bhavsar, Wound Healing (Basics) Fetal Wound Healing • Rapid • Efficient • Perfect • Scar less Dhaval Bhavsar, Wound Healing (Basics) Fetal Wound Healing • Involves mechanisms similar to cell migration and proliferation during embryonic stage of fetal life • No inflammation • Wound contraction takes place but no scarring Dhaval Bhavsar, Wound Healing (Basics) Abnormal Healing • Hypertrophic scar • Keloid • Chronic non-healing wound Dhaval Bhavsar, Wound Healing (Basics) Hypertrophic Scar • Imbalance in collagen production and degradation • Either over production OR • Low degradation • Red, elevated scars http://www.51qe.cn/pic/30/12/17/42/b/01701.jpg Dhaval Bhavsar, Wound Healing (Basics) Hypertrophic Scar • Usually along tension lines • Contracture occurs more in areas with laxity http://surgclerk.med.utoronto.ca/Burn/images/scar1.jpg Dhaval Bhavsar, Wound Healing (Basics) Keloid • African>Asians> Caucasians • Comparable to malignant growth • Extends beyond wound http://www.emedicine.com/derm/images/917dumbellear.jpg margins Dhaval Bhavsar, Wound Healing (Basics) Non healing Wound • Wound that fails to progress through an orderly sequence of repair in a timely fashion • Arbitrary time point: 3-4 http://www.uth.tmc.edu/anes/wound/images/figure_1.jpg weeks Dhaval Bhavsar, Wound Healing (Basics) Causes of Delayed Wound Healing • Infection • Tissue hypoxia • Repeated trauma • Presence of necrotic tissue or foreign body • Systemic causes • Diabetes • Malnutrition- protein • Immunodeficiency Dhaval Bhavsar, Wound Healing (Basics) Common Non-healing Wounds Diabetic wound Pressure sore Venus ulcer http://medicine.ucsd.edu/ http://health-pictures.com/images/Decubitus.jpg http://www.bu.edu/woundbiotech/bioengineered Dhaval Bhavsar, Wound Healing (Basics) Wound Healing & Nutrition • Vitamin C and A Investigate • Serum protein • Protein • Hemoglobin Essential amino acids • Micronutrients Mg, Cu, Zn, Fe Dhaval Bhavsar, Wound Healing (Basics) Tendon Repair Gross Examination Intermediate phase Early phase J Hand Surg [Am]. 2003 Sep;28(5):814-23 Late phase Dhaval Bhavsar, Wound Healing (Basics) Nerve Repair http://www.northland.cc.mn.us/biology/AP2Online/Fall2001/Nervous/images/neuron_regeneration.gif Dhaval Bhavsar, Wound Healing (Basics) Bone Repair http://137.222.110.150/calnet/musculo/image/fracture%20repair%20scheme.jpg Dhaval Bhavsar, Wound Healing (Basics) THANK YOU Dhaval Bhavsar, Wound Healing (Basics) .
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