Wound Healing Stages

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Kerry Reed
5 years ago
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2 Normal Skin

Wound Healing Stages Stages overlap Chronic wounds are stalled in the inflammatory phase COLLAGEN MATURATION MATRIX METALLOPROTEINASES ENDOTHELIAL CELLS

3 Wound Healing Stages Stages overlap Chronic wounds are stalled in the inflammatory phase COLLAGEN MATURATION MATRIX METALLOPROTEINASES ENDOTHELIAL CELLS EPITHELIAL CELLS MATRIX PROTEINS FIBROBLASTS PLATELETS FIBRIN LYMPHOCYTES MACROPHAGE NEUTROPHILS INFLAMMATORY CYTOKINES PROTEOGLYCANS CHRONIC WOUNDS Time after wounding

4 The Chronic Wound Epidemic million people living in the United States have at least one non-healing wound 10-15% of diabetics develop lower extremity ulcers of some sort during their lifetime 100,000 limb amputations will be performed on diabetics this year due to non-healing wounds The prevalence of pressure ulcers in hospitals and skilled nursing facilities in the US has been reported to range from 2.4% - 23% Treating chronic wounds costs at least $5-10 billion per year in the US

5 Lack of Safe Affordable Treatment Options Regranex Gel (becaplermin) 0.01% recombinant platelet-derived growth factor (PDGF) The only FDA-approved growth factor treatment for chronic wounds Black box 2008 Cost prohibitive for many patients $586 per 15g tube (requires 2-3 tubes for a 2 cm 2 wound) Wound Vacuum Assisted Closure (VAC ) Limits patient movement Expensive REGRANEX Gel is a registered trademark of Ortho-McNeil Pharmaceutical, Inc. V.A.C. is a registered trademark of Kinetic Concepts, Inc.

6 Hyaluronic Acid (HA) Glycosaminoglycan consisting of repeating units of D-glucoronic acid and - acetyl-d-glucosamine. Found in almost every vertebrate organ and is particularly abundant in skin where it makes up a large percentage of dermal extracellular matrix. [C14 H21 N O11] n where n=1-25 thousand Highly hygroscopic thus contributing to tissue hydration. Interacts with cell surface receptors influencing cell migration and proliferation.

dryness observed in aged skin Levels decrease after UV exposure After wounding HA breakdown products stimulate keratinocytes to

7 Hyaluronic Acid (HA) and the Skin Found in both the epidermis and dermis Fetal wounds which heal quickly without scarring have high levels of HA Levels decrease in the epidermis with age In the elderly HA is found only in the upper dermis contributing to the dryness observed in aged skin Levels decrease after UV exposure After wounding HA breakdown products stimulate keratinocytes to release -defensin 2, thus protecting the skin from infection Critical to wound healing web-books.com/elibrary/medicine/physiology/skin/skin.htm

8 Hyaluronic acid (HA) is Crucial for Proper Wound Healing INJURY Upon injury: Hyaluronan synthase expression is upregulated resulting in increased levels of HA CD44 TLR4 MD2 Rhamm CD44 HA breaks down and is released Lower weight HA signals through TLR4 with accessory molecules MD-2 and CD44 Lower molecular weight HA also binds receptor for hyaluronan mediated motility expressed protein (Rhamm) resulting in increased cell migration High molecular weight HA is broken down into smaller subunits by hyaluronidase Tyrosine kinases ERMs Ras NF- B P38? ERK? PI3 kinase? MyDBB P38 JNK ERK 1,2 IRAKs TRAF6 NF- B Plasma membrane Cell migration Subunits bind to and activate cell receptors resulting in signal transduction leading to: Matrix metalloproteinase (MMP) expression Cell migration Angiogenesis Inflammation SOCS3 MMP-13 TGF- 2 Inflammatory cytokines interferon

9 Ionic Polymer Matrix (IPM) Wound Gel -Delivering a more potent hyaluronic acid Cleared for the US market in 2002 as a medical device 2.5 % sodium hyaluronate (higher concentration than that of other products): non-immonogenic Sodium Hyaluronate Other ingredients: hydroxyethylcellulose, methylparaben glycol, polyethylene glycol (all considered safe by regulatory authorities and readily available without prescription)

10 Ionic Polymer Matrix (IPM) Wound Gel -Delivering a more potent hyaluronic acid Cleared by the FDA for the following indications: OTC: minor abrasions and cuts Under supervision of a healthcare professional: leg ulcers, pressure ulcers, diabetic ulcers, venous stasis ulcers, and debrided wounds Sodium Hyaluronate Clear, viscous, odorless, and able to absorb large amounts of fluid making it useful for the removal of excessive wound fluid exudate

11 Ionic Polymer Matrix (IPM) Wound Gel -Delivering a more potent hyaluronic acid Penetrates all layers of the skin Uses patented IPM technology resulting in deeper skin penetration and wound hydration Clinically proven to speed healing of refractory ulcers Sodium Hyaluronate

12 Partial Thickness Excisional Porcine Wound Study % of wounds healed after 5 days 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 87% L.A.M. Ulcer Matrix 7% Placebo 53% Leading Marketed Product IPM Wound gel was superior to placebo and Hyalofill at days 3,5 and 6. Graph represents percent of wounds healed at day 5. Hyalofill is a registered trademark of ConvaTec Mertz PM, Davis SC, et al. University of Miami School of Medicine Porcine Model Study

13 Clinical Evidence (overview) 27 patients included in study 53 non-healing ulcers treated 13 different types of ulcer 1 ml gel to 1 cm area ulcer; maximum 4ml/day 25 weeks

14 .The Proof Calciphylaxis Ulcer 33 days

15 .continued Stasis Ulcer 34 days

16 .continued Rheumatoid Ulcer 64 days

17 .continued Diabetic Ulcer 66 days

18 Patient Questionnaire 27 patients responded How difficult was your wound to heal before using IPM Wound Gel? Do you feel IPM Wound Gel aided in healing?

19 Ionic Polymer Matrix (IPM) unique characteristics IPM encapsulates molecules Can be used for transdermal delivery to targeted areas and release into systemic circulatory system Molecule of choice

20 Personal Female Lubricant Incorporates vitamin B3 (Niacin) Matrix has proven effective in areas including: Vaginal Dryness Pain during intercourse Absence of feeling or sensation THE FEMALE LUBRICANT MATRIX MAY BE USED FOR PERSONAL INTIMATE PURPOSES BY WOMEN OF ALL AGES

21 Motion Sickness A patch system Controlled release of the motion sickness drug over a 24- hour period Maximum protection against motion sickness IPM transdermal method requires substantially smaller amount of drug as compared to the oral dosage form Patch wearers experience little or no drowsiness

Pain Relief Incorporates diclofenac sodium, a nonsteroidal antiinflammatory (NSAID) with analgesic and antipyretic properties Used by patients with

22 Pain Relief Incorporates diclofenac sodium, a nonsteroidal antiinflammatory (NSAID) with analgesic and antipyretic properties Used by patients with moderate to severe arthritic pain Onset of pain relief is rapid (10-15 minutes) and longlasting (4-6 hours) Transdermal delivery has fewer side-effects

23 Conclusions Hyaluronic acid (HA) is depleted in the chronic wound IPM Wound Gel delivers a high concentration of HA directly to the wound bed Clinically proven to speed healing of non-healing ulcers Well tolerated by patients Unique patented formula 5 US patents IPM Wound Gel s 2.5% HA far exceeds concentrations in other commercially available products

24 ..continued Unique matrix has multiple uses Widespread possible applications Pain relief Motion sickness Female lubricant

Adjunctive Therapies: The Use of Skin Substitutes and Growth Factors in Venous Leg Ulceration (VLU)

Adjunctive Therapies: The Use of Skin Substitutes and Growth Factors in Venous Leg Ulceration (VLU) Sami Khan, MD FACS Associate Professor of Surgery Division of Plastic and Reconstructive Surgery SUNY-Stony