Indi Adressing Final


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Wound Care Dressing overview presented to a physician and nursing class at CMC in Vellore,India

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  • Indi Adressing Final

    1. 3. Ambrose Pare 1520 to 1590 “ I dress the wounds God Heals them”
    2. 5. Wound Dressing Basics <ul><li>Thorough wound cleansing is the first step with each dressing change. </li></ul>
    3. 6. Wound Dressing Basics <ul><li>Fill wound cavities/dead space </li></ul>
    4. 7. Wound Dressing Basics <ul><li>Protect periwound skin </li></ul>
    5. 8. Wound Dressing Basics <ul><li>Avoid adhesives on friable skin </li></ul>
    6. 9. Wound Care Basics <ul><li>Always use a skin prep and allow to dry before applying adhesive </li></ul>
    7. 10. Three Key Components of Local Wound Care <ul><li>Moist interactive healing </li></ul><ul><li>Debridement </li></ul><ul><li>Bacterial balance/prolonged inflammation </li></ul>
    8. 14. Comparison of maintaining moist versus open wound <ul><li>Moisture increases re-epithelialization by 30 – 50% </li></ul><ul><li>Moisture increases collagen synthesis by 50% </li></ul><ul><li>Rate of epithelialization with moisture 2 to 5 times faster </li></ul><ul><li>Marked decrease in wound surface fluid loss </li></ul>
    9. 15. Advantages of moist wound surface <ul><li>Decrease in surface dessication and eschar formation </li></ul><ul><li>Increase in local growth factor production </li></ul><ul><li>Activation of surface proteases to remove devitalized tissue </li></ul><ul><li>Enhanced wound surface immune defenses </li></ul><ul><li>Increased rate of angiogenesis and fibroblast proliferation </li></ul><ul><li>Increased proliferation and migration of epithelial cells along thin water layer </li></ul>
    10. 16. Moisture is required for: <ul><li>Activity of growth factors </li></ul><ul><li>Activity of surface proteolytic enzymes </li></ul><ul><li>Surface oxygen delivery </li></ul><ul><li>More effective nutrient delivery </li></ul>
    11. 17. Potential complications of moist healing <ul><li>Infection? Does not appear to be increased in a clean wound, even with nonviable tissue on the surface </li></ul><ul><li>Skin maceration? Does not appear to occur unless exudate is allowed to occur </li></ul><ul><li>Hypergranulation? Seems to be less with moist healing as surface inflammation is less </li></ul><ul><li>Pain? Pain is less </li></ul>
    12. 19. Moist Wound Healing The moist environment provided by covering a wound (left) allows the epidermal cells to move easily across the wound surface, healing the wound. In a dry environment (right), the epidermal cells must tunnel down to a moist level and secrete enzymes to lift the scab away from thw wound surfae before the cells can migrate and begin to allow healing to occur.
    13. 21. Gauze Dressing <ul><li>Worldwide still the most common dressing material used </li></ul><ul><li>In the chronic wound setting usually employed as “wet to dry” or “wet to moist”. </li></ul><ul><li>Wound is packed with a moistend gauze, covered with a secondary dry dressing. </li></ul><ul><li>Typically changed once or twice daily </li></ul><ul><li>Classically described as a way to mechanically debride a wound. </li></ul>
    14. 22. Gauze dressings: wet to dry <ul><li>Heat loss from wound </li></ul><ul><li>Poor bacterial barrier; to and from the wound </li></ul><ul><li>Labour intensive and costly </li></ul><ul><li>don’t work! </li></ul>
    15. 23. Gauze dressings: heat loss <ul><li>Open wound 21 C, gauze covered 25 C, semi occlusive 33 C to 35 C </li></ul><ul><li>Cooling causes local vasoconstriction </li></ul><ul><li>Cooling causes impairment of lekocyte mobility and phagocytic efficiency </li></ul><ul><li>Oxygen dissociation curve shifts left, RBC has increased affinity for oxygen </li></ul>
    16. 24. Gauze dressings: poor bacterial barrier <ul><li>Provide no physical barrier to entry of exogenous bacteria </li></ul><ul><li>In vitro bacteria able to penetrate 64 layer thick gauze barrier, moistened even worse </li></ul><ul><li>Literature review of 3047 wounds, overall infection rate semi occlusive dressings 2.6%, gauze 7.1% </li></ul><ul><li>Dry and moistend gauze disperse bacteria from the wound into surrounding air with dressing changes. Bacteria remain aerosolized for upto 30 minutes </li></ul>
    17. 26. The real cost of wound care <ul><li>The price of the dressing </li></ul><ul><li>The labor cost of having a healthcare professional change the dressing </li></ul><ul><li>Indirect cost of ancillary supplies (eg, gloves, biohazard disposal) </li></ul><ul><li>The cost of duration of care </li></ul>
    18. 27. Gauze: why still popular? <ul><li>One size fits all, readily available, familiarity, tradition, percieved as inexpensive </li></ul><ul><li>Advanced dressings don’t easily fit, must stockpile multiple products, multiple sizes </li></ul><ul><li>Multiple choices daunting </li></ul>
    19. 28. Gauze dressings: don’t work <ul><li>Wound dessication </li></ul><ul><li>Painful </li></ul><ul><li>Nonselective debridement removes healthy and diseased tissue with change </li></ul>
    20. 31. The Indian Wound Care Market: A review 2004 Frost and Sullivan Market Insight <ul><li>High rural to urban ratio </li></ul><ul><li>Innumerable geo – socio – cultural variables </li></ul><ul><li>Core development issues like poverty, illiteracy, and nutrition </li></ul>
    21. 32. The Indian Wound Care Market: A review 2004 Frost and Sullivan Market Insight <ul><li>Combined investment in health by centre and state governments is just 1.3% of GDP </li></ul><ul><li>Reimbursement is negligible, though privatization of the insurance sector has helped </li></ul><ul><li>Of 16,000 hospitals 60% are in the public sector </li></ul><ul><li>The populace has low purchasing power, combined with low health protection </li></ul>
    22. 33. Wound Dressings Technology and product proliferation varies by geography, usually as a function of economics and health care policy.
    23. 34. History Of Dressings
    24. 35. The perfect dressing <ul><li>Keeps wound moist </li></ul><ul><li>Promotes wound healing </li></ul><ul><li>Mechanical protection </li></ul><ul><li>Nonadherant to wound bed </li></ul><ul><li>Change w/o pain </li></ul><ul><li>Absorbs excess exudate </li></ul><ul><li>Allows gas exchange </li></ul><ul><li>Barrier to bacterial access </li></ul><ul><li>Ease of use </li></ul><ul><li>Cost (overall) </li></ul>
    25. 37. Biology of Chronic Wounds Wound Exudate Burden
    26. 38. Chronic wound fluid <ul><li>Elevated proinflammatory cytokines </li></ul><ul><li>High protease activity </li></ul><ul><li>Decreased levels of natural inhibitors to MMPs </li></ul><ul><li>Diminished growth factor activity </li></ul>
    27. 39. Biology of Chronic Wounds Exudate Burden <ul><li>Blocks the proliferation and activity of certain cell types, fibroblasts and keratinocytes </li></ul><ul><li>MMPs and proteases in high concentrations </li></ul><ul><li>Proprietary growth factors and bioengineered skin do not fare well well in wound microenvironment that contains high amounts of exudate </li></ul>
    28. 40. Managing moisture balance
    29. 42. Transparent films
    30. 43. Transparent films <ul><li>Absorbency = 0 </li></ul><ul><li>Wear time = 7 days </li></ul><ul><li>Polymer sheets coated with adhesive </li></ul><ul><li>Impermeable to liquid, water, bacteria </li></ul><ul><li>Permeable to moisture vapor and atmospheric gases </li></ul><ul><li>Clear design allows visualization </li></ul><ul><li>Re-epithelialization/protectant/cover dressing </li></ul>
    31. 44. Transparent Films <ul><li>Designed around initial moist wound care concepts (Winters) </li></ul><ul><li>Some pain relief </li></ul><ul><li>Aggressive adhesive can be a problem, trauma </li></ul><ul><li>Drainage can collect and disrupt barrier </li></ul>
    32. 45. Hydrogels
    33. 46. Hydrogels <ul><li>Absorbency = 1+ </li></ul><ul><li>Wear time = 12 to 72 hours </li></ul><ul><li>Formulations of water , polymers, propylene glycol </li></ul><ul><li>Designed to donate moisture to dry wound </li></ul><ul><li>Comes in amorphous,gauze impregnated sheets </li></ul><ul><li>Good for debridement, granulation,epithelialization </li></ul>
    34. 47. Hydrogels <ul><li>Provide high water content in a gel lattice that renders them nonadherent and soothing </li></ul><ul><li>Provide the wound with moisture </li></ul>
    35. 48. Hydrogel
    36. 50. Hydrogels
    37. 51. Hydrocolloids
    38. 52. Hydrocolloids <ul><li>“ water loving” </li></ul><ul><li>Elastic, adhesive and gelling agents ( ie. Pectin or gelatin) </li></ul><ul><li>Change once every 3 to 7 days </li></ul><ul><li>Frequency of change depends on drainage, shear, and incontinence…) </li></ul>
    39. 53. Hydrocolloids <ul><li>Absorbency = 2+ </li></ul><ul><li>Wear time 3 to 7 days </li></ul><ul><li>Composed of gelatin , pectin, carboxymethylcellulose </li></ul><ul><li>Vary in thickness, margins </li></ul><ul><li>Good for granulation, debridement, epithelialization; autolytic debridement </li></ul>
    40. 54. Hydrocolloid
    41. 56. Debridement <ul><li>Surgical, sharp </li></ul><ul><li>Enzymatic </li></ul><ul><li>Autolytic </li></ul>
    42. 57. Importance of Debridement Removal of callus and necrotic tissue Decreasing the bacterial burden Removal of phenotypically altered cells: the cellular burden
    43. 58. Autolytic debridement <ul><li>The use of synthetic dressings to cover a wound and allow eschar to self-digest by the action of enzymes present in wound fluid </li></ul><ul><li>Utilizes the bodies own enzymatic machine to dissolve necrotic tissue within the wound, selective </li></ul><ul><li>Moist environment accelerates the process </li></ul><ul><li>Little or no pain </li></ul><ul><li>Sloooow </li></ul><ul><li>Hydrocolloids, hydrogels, transparent films, and alginates </li></ul>
    44. 59. Autolytic Debridement: advantages <ul><li>Very selective, with no damage to surrounding skin </li></ul><ul><li>Safe </li></ul><ul><li>Effective, versatile and easy to perform </li></ul><ul><li>Little or no pain </li></ul>
    45. 60. Autolytic Debridement: disadvantages <ul><li>Not as rapid as surgical debridement </li></ul><ul><li>Wound must be monitored closely for signs of infection </li></ul>
    46. 61. Calcium Alginates <ul><li>Absorbency = 4+ </li></ul><ul><li>Wear time 1 to 7 days </li></ul><ul><li>Natural polysaccharide derived from seaweed </li></ul><ul><li>Converts to gel with fluid contact </li></ul><ul><li>Rope, sheets, conformable packing </li></ul><ul><li>Wicks vertically </li></ul><ul><li>Gel block to edges </li></ul><ul><li>Good for highly exudating wounds, granulation;hemostasis and odor control functions </li></ul>
    47. 62. Calcium alginate
    48. 64. Calcium Alginate
    49. 65. Foams <ul><li>Absorbency = 4+ </li></ul><ul><li>Wear time 1 to 7 days </li></ul><ul><li>Foamed solutions of polymers, polyurethane </li></ul><ul><li>Vary in thickness with or without adhesives </li></ul><ul><li>Good for highly exudating wounds in granulation stage </li></ul>
    50. 66. Foam dressings
    51. 68. Collagens <ul><li>Absorbency = 1 – 4+ </li></ul><ul><li>Wear time 1 – 5 days </li></ul><ul><li>Exogenous collagen derived from porcine, bovine sources </li></ul><ul><li>Available in sheets, particles, powders, pastes </li></ul><ul><li>Requires secondary dressing </li></ul>
    52. 69. Promogran <ul><li>Sterile freeze dried matrix, 45% cellulose,55% collagen </li></ul><ul><li>Packaged as a sheet </li></ul><ul><li>In prescense of wound exudate the matrix absorbs liquid and forms a soft, comortable biodegradable gel </li></ul><ul><li>Binds and inactivates matrix mettalloproteases (MMPs) </li></ul>
    53. 73. Biology of Chronic Wounds Bioburden
    54. 75. Bioburden continum <ul><li>Colonization </li></ul><ul><li>Critical colonization </li></ul><ul><li>Wound infection </li></ul>
    55. 76. Colonization <ul><li>All chronic wounds that heal will do so in a colonized state </li></ul><ul><li>Infection in chronic wounds reflects host susceptibilty </li></ul><ul><li>Significantly greater chance of impaired wound healing when four or more species present </li></ul>
    56. 77. Critical colonization <ul><li>10 to the 5 th colonization has no confirmed connection to the threshold or degree of immune response or to healing </li></ul><ul><li>Infection diagnosis often a retrospective diagnosis </li></ul><ul><li>Evidance supports the fact that delayed healing in a chronic wound that has no signs of clinical infection, suggestive of critical colonization, is directly related to microbial bioburden, notably nonhemolytic strep and anaerobes. </li></ul><ul><li>Where wounds are static or exudate levels high, critical colonization or infection should be suspected </li></ul>
    57. 78. Biofilm formation
    58. 79. Critical colonization/infection <ul><li>Microbes consume valuable nutrients and oxygen </li></ul><ul><li>White cell function is impaired by short chain fatty acids, endotoxins and subsequent interleukins(TNF), matrix metalloproteases </li></ul><ul><li>Oxygen free radical production </li></ul><ul><li>Fibroblast production decreased and delayed, decreased scar strength </li></ul>
    59. 82. Wound cleansing <ul><li>Purpose: remove excess exudate, foreign bodies (retained dressings), necrotic tissue, wound edge crusting/debris </li></ul><ul><li>Should include periwound skin </li></ul><ul><li>Includes: debridement, pressure irrigation, moistend wipe </li></ul>
    60. 83. Wound cleansing <ul><li>Sterile normal saline </li></ul><ul><li>Tap water – “the fluid of first choice” </li></ul><ul><li>Hall Angerans et. al, 1992 “tap water presents no quantifiable infection risk” </li></ul><ul><li>Chrintz et. al,1989 in a study of 1,200 head and neck wounds demonstrated no increase in wound infection rate when patients showered postoperatively </li></ul>
    61. 85. Topical antibiotics <ul><li>“ use of topical antibiotics is not justified for the routine treatment of colonized or infected wounds” </li></ul><ul><li>Can provoke delayed hypersensitivity response </li></ul><ul><li>Select for resistant bacterial strains </li></ul><ul><li>“ routine use of topical antibiotics in the management of clinically infected leg ulcers has been shown to be of no benefit and some evidance shows it may be harmful because it encourages colonization by resistant organisms” </li></ul>
    62. 86. Topical antibiotics – metronidazole <ul><li>Indicated for malodorous fungating wounds </li></ul>
    63. 87. Topical antibiotics - mupirocin <ul><li>Narrow spectrum topical antibiotic developed to eradicate MRSA (nasal) </li></ul><ul><li>Mupirocin low level resistance now common, high level resistance documented </li></ul>
    64. 88. Topical antibiotics - TAO <ul><li>Neomycin, polymyxin, bacitracin </li></ul><ul><li>Inhibit coag neg Staph, Pseudomonas aeruginosa </li></ul><ul><li>S. aureus resistance 5% </li></ul><ul><li>TAO use must be balanced by the well known risks of sensitization, particularly when using neomycin, bacitrain </li></ul>
    65. 90. Antiseptics <ul><li>A disinfectant substance used on skin and wounds that either kill (cidal) or prevents multiplication (static) of potentially pathologic organisms </li></ul><ul><li>Multiple targets, broad spectrum of activity (bacteria, fungi,viruses,prions) </li></ul><ul><li>Most common: povidine iodine, chlohexidine, acetic acid, hydrogen peroxide, silver, sodium hypochlorite </li></ul>
    66. 91. Antiseptics <ul><li>Significant potential for cell toxicity (fibroblasts, keratinocytes,leukocytes) </li></ul><ul><li>Toxicity = formulation, concentration, exposure </li></ul><ul><li>Continue to play a role in surgical skin preps and the heavily contaminated wound </li></ul>
    67. 92. Antiseptics <ul><li>Broader spectrum that antibiotics </li></ul><ul><li>Bacterial resistance may be less of an issue </li></ul><ul><li>Incorporated into dressings allows for dilution and slow release therefore decreased toxicity </li></ul><ul><li>Iodine, silver, and honey currently meet US and EU safety requirements </li></ul>
    68. 93. The Ideal Antiseptic <ul><li>Effective against likely contaminants and pathogens </li></ul><ul><li>Fast acting with prolonged activity </li></ul><ul><li>Inexpensive, widely available </li></ul><ul><li>Incapable of promoting bacterial resistance </li></ul><ul><li>Minimal systemic absorption </li></ul><ul><li>Noncarcinogenic, nontoxic </li></ul>
    69. 94. The Antiseptic Dilemma <ul><li>Very little good research regarding their use </li></ul><ul><li>An animal model for the chronic wound does not exist </li></ul>
    70. 96. Iodine <ul><li>Natural element discovered in 1811 </li></ul><ul><li>Molecular iodine very toxic to living tissue </li></ul><ul><li>Formulations of iodine and a carrier molecule facilitates decreased iodine availability </li></ul><ul><li>Povidine iodine = molecular iodine plus polyvinylpyrrolidine </li></ul>
    71. 97. Povidine Iodine <ul><li>Solution, cream, ointment, scrub </li></ul><ul><li>Scrub has detergent and should only be used on intact skin </li></ul><ul><li>Effective in reducing the bacterial load </li></ul><ul><li>1% solution appears optimal (toxicity is concentration dependant) </li></ul>
    72. 99. Iodine - cadexomer <ul><li>Spherical hydrophilic (water loving) beads of cadexomer starch which contain iodine </li></ul><ul><li>Highly absorbent </li></ul><ul><li>Release iodine slowly into the wound </li></ul><ul><li>Sheet, gel, spray </li></ul><ul><li>Iodosorb,iodoflex </li></ul>
    73. 101. Iodosorb/iodoflex indications <ul><li>Chronic exuding wounds : leg ulcers, pressure ulcers, diabetic ulcers </li></ul><ul><li>Especially when critical colonization suspected (MRSA, Pseudomonas) </li></ul><ul><li>Dressing change dictated by color loss usually at 3 days </li></ul><ul><li>Apply 3 mm thick, covered with a secondary dressing </li></ul><ul><li>Removal facilitated by gentle irrigation </li></ul>
    74. 102. Iodosrb/Iodoflex contraindictions <ul><li>Iodine sensitivity </li></ul><ul><li>Hashimoto’s thyroiditis </li></ul><ul><li>Non toxic nodular goiter </li></ul><ul><li>Avoid prolonged use in renal insufficiency and history of thyroid disorder </li></ul><ul><li>Pregnancy </li></ul><ul><li>Hildren </li></ul><ul><li>Lithium use should not exceed 3 months </li></ul>
    75. 103. Iodine - cadexomer <ul><li>Studies (9) support that these dressings create environment of less pain, less exudate, more rapid development of granulation tissue </li></ul><ul><li>Positive effects on epidermal regeneration </li></ul><ul><li>May be a potent agent against Staph aureus, MRSA (multiple strains differing iodine kill levels, in vitro vs in vivo) </li></ul>
    76. 104. Hydrogen Peroxide <ul><li>Limited bactericidal effectiveness in vivo </li></ul><ul><li>Toxic to fibroblasts </li></ul><ul><li>Impairs wound microcirculation </li></ul><ul><li>Mechanical effect of “fizz” questionable </li></ul><ul><li>Avoid in newly formed epithelium </li></ul>
    77. 105. Hydrogen Peroxide <ul><li>3 % solution is most commonly used wound antiseptic </li></ul><ul><li>Catalases in wound tissue decrease bactericidal effect </li></ul><ul><li>In vitro broad spectrum antibacterial efficacy (gram +) </li></ul><ul><li>Few studies look at it’s efficay </li></ul>
    78. 106. Honey <ul><li>Evidence of antibacterial activity against upto 70 different bacterial species </li></ul><ul><li>Manuka Honey active against MRSA, and VRE ( vancomycin resistant enterococci) </li></ul><ul><li>Mechanism? </li></ul><ul><li>Very little good literature </li></ul>
    79. 107. Chlorhexidine <ul><li>1946 </li></ul><ul><li>Widely used in hand washing, surgical scrubs </li></ul><ul><li>Rapid bactericidal activity </li></ul><ul><li>Active against Stap aureus, Pseudomonas </li></ul><ul><li>MRSA rseistance has been reported </li></ul>
    80. 108. Antiseptics <ul><li>Povidine- iodine, chlorhexidine, hydrogen peroxide, and 0.25% acetic acid have been shown to interfere with fibroblast formation and epithelial growth </li></ul><ul><li>The selected use of topical antiseptics should be reserved for wounds that do not have the ability to heal, or for the time – limited use in wounds where bacterial burden is more important than cellular toxicity. </li></ul>
    81. 109. Wounds without the ability to Heal
    82. 110. Wounds where bacterial burden outweighs cellular toxicity
    83. 111. Four stages of life
    84. 112. Silver <ul><li>Ancient Greece and Rome silver coins were dropped in water to act as a disinfectant </li></ul><ul><li>1884 1% silver nitrate eye drops used to eliminate blindness caused by postpartum infection </li></ul><ul><li>1964,1968 silver sulfadiazine (SSD) usedin burns </li></ul>
    85. 113. Silver <ul><li>Acts as a heavy metal impairing bacterial electron transport </li></ul><ul><li>Occurs only when silver ion Ag+ available to enter the cell at correct concentration </li></ul><ul><li>In any formulation the way silver is incorporated and how it interacts with micro organisms over time is critical </li></ul>
    86. 114. Silver <ul><li>Few if any clinical evidance study results are available to support specific silver products </li></ul><ul><li>Genetic basis of bacterial resistance to silver has been identified </li></ul><ul><li>80 known stains of MRSA, bacteriacidal activity against all strains was achieved only after 60 ppm silver concentration </li></ul><ul><li>SSD delivers in excess of 3,000 ppm, Aqucel Ag 1 to 2 ppm, Actioat 50 to 100 ppm ( deionized purified sterile water!) </li></ul>
    87. 118. Honey <ul><li>C.50AD Dioscorides described honey as “good for all rotten and hollow ulcers” </li></ul><ul><li>Inhibitory to 60 bacterial species, also antifungal </li></ul><ul><li>Hyperosmolar </li></ul><ul><li>Parodoxically dilution increases antibacterial proprties by increasing hydrogen peroxide production </li></ul><ul><li>Manuka Honey from New Zealand, unique phytochemical comonent </li></ul>
    88. 119. Critical colonization <ul><li>Colonized wounds are present for longer, are larger and have significantly delayed healing time when compared with ulcers where n bacterial growth is found </li></ul><ul><li>“ early and appropriate intervention using silver- or iodine- containing dressings in particular can avoid progression to critical colonization and infection, thus potentially improving healing rates and reducing the risk of cross contamination” </li></ul>
    89. 125. Negative pressure wound therapy – proposed mechanisms <ul><li>Remove exudate </li></ul><ul><li>Provides a moist environment </li></ul><ul><li>Removes slough </li></ul><ul><li>Decrease wound bacterial burden (?) </li></ul><ul><li>Reduces local edema </li></ul><ul><li>Increased perfusion pressure </li></ul><ul><li>Increases production of growth factors, promotes leukocytes, fibroblasts </li></ul>
    90. 126. Negative pressure wound therapy <ul><li>“ Kremlin papers”, 5 articles, 1986 to 1998 </li></ul><ul><li>Vacuum assisted debridement, -100 mmHg, Rx time 5 to 10 min; significant reduction in bioburden, and improved wound healing </li></ul><ul><li>Vacuum assisted treatment of lactation mastitis, negative pressure treatment 2x daily; improved ab titers, increased t cells, reduced bacterial load and septic complications, significantly reduced scarring </li></ul>
    91. 127. V.A.C. <ul><li>1997 Monykwas and Argenta described their experience with subatmospheric pressure delivered to open wounds for a period of upto 48 hours </li></ul><ul><li>Interfaced with polyurethane sponge which allows for even distribution of pressure </li></ul>
    92. 131. Negative pressure wound therapy
    93. 133. Living Skin Equivalents
    94. 134. Why Cell Therapy for Chronic Wounds? <ul><li>Smartness – cells are able to adapt to their micro environment </li></ul><ul><li>Knowledge base – cells may bypass our lack of knowledge about what is required in specific situations </li></ul><ul><li>Commercially available – cells are readily available as primary cultures, off the shelf products </li></ul><ul><li>Manipulation – cells can be genetically manipulated </li></ul>
    95. 135. Apligraf ® — Manufacturing Process Human Dermal Fibroblasts Connective Tissue Proteins Dermal Matrix Human Epidermal Keratinocytes Apligraf Data on file, Organogenesis Inc., Canton, MA.
    96. 136. Parentau NL, et al. J Cell Biochem . 1991;45:245-251.
    97. 137. Apligraf ® Why Fibroblasts and Keratinocytes?
    98. 138. Components of Wound Healing Injury Hours Days Weeks Coagulation Process Inflammatory Process Migratory/ Proliferative Process Remodeling Process Platelets Platelets Macrophages Neutrophils Fibroblasts Cell Types Involved Kane DP, Krasner D. Inc. Chronic Wound Care . 2nd ed. Health Management Publications Inc; 1997:1-4. Macrophages Lymphocytes Fibroblasts Epithelial cells Endothelial cells
    99. 140. Role of Fibroblasts in Wound Healing Fibroblast Migration/ Proliferation Protease release ECM production Growth factor/ cytokine production Angiogenesis ECM = extracellular matrix.
    100. 142. Role of Keratinocytes in Wound Healing ECM = extracellular matrix. Keratinocyte Migration/ Proliferation Matrix synthesis regulation ECM production Growth factor/ cytokine production Angiogenesis
    101. 143. Potential Mechanisms of Action of Apligraf ® <ul><li>Delivery of young, active fibroblasts and keratinocytes </li></ul><ul><li>Demonstrated to show persistence of cells in the wound out to 6 weeks 1 </li></ul><ul><li>Production of new matrix material (fibronectin, vitronectin, proteoglycans) and cytokines and growth factors </li></ul><ul><li>Recruitment of other cell types, including stem cells, to the non-healing wound </li></ul>Hypotheses: Actual mechanisms of action are not known. 1. Griffiths M, et al. Tissue Eng . 2004 Jul-Aug;10(7-8):1180-95.
    102. 144. Apligraf ® FDA Approved for the Treatment of Venous and Diabetic Neuropathic Ulcers
    103. 145. A B D C Progression of Healing in a Venous Ulcer After Extensive Debridement and Apligraf Treatment
    104. 146. Apligraf ® FDA Approved for the Treatment of Venous and Diabetic Neuropathic Ulcers
    105. 147. Diabetic Ulcer Healed With Apligraf ® : Treatment Sequence
    106. 148. Apligraf ® FDA Indications <ul><li>Indicated for the treatment of noninfected partial- and full-thickness venous leg ulcers with standard therapeutic compression </li></ul><ul><ul><li>Ulcers that have not adequately responded to at least 4 weeks of conventional therapy </li></ul></ul><ul><li>Indicated for the treatment of full-thickness neuropathic diabetic foot ulcers when used with standard diabetic foot ulcer care </li></ul><ul><ul><li>Ulcers that have not adequately responded to at least 3 weeks of conventional therapy </li></ul></ul>