• 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
• 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
• 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)