Faculty. The Chronic Wound Management and Reconstruction Continuum: Strategies to Promote Wound Healing. Accreditation. Faculty Disclosures

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1 The Chronic Wound Management and Reconstruction Continuum: Strategies to Promote Wound Healing Sponsored by North American Center for Continuing Medical Education, LLC, An HMP Communications Holdings Company Supported by an Educational Grant from KCI Charles A. Andersen, MD, FACS Clinical Professor of Surgery, UW, USUHS Chief Vascular/Endovascular/Limb Preservation Surgery Service Medical Director, Wound Care Clinic Madigan Army Medical Center Tacoma, Washington John C. Lantis, II, MD Associate Clinical Professor of Surgery Columbia University Chief of Division, Vascular/ Endovascular Surgery St. Luke s-roosevelt Hospital New York, New York Faculty Alexander Reyzelman, DPM Co-Director, UCSF Center For Limb Preservation Associate Professor, Department of Medicine California School of Podiatric Medicine at Samuel Merritt University San Francisco, California Thomas Serena, MD CEO & Medical Director Serena Group Norwell, Massachusetts Faculty Disclosures Accreditation Dr. Andersen: Speaker KCI, Organogenesis Dr. Lantis: Consultant Healthpoint, KCI, Smith & Nephew; Principle investigator Healthpoint, Smith & Nephew Dr. Reyzelman: Consultant KCI; Speaker KCI, Shire Dr. Serena: Grant/research support Celleration, CoDa Therapeutics, EnzySurge, Healthpoint, HealOr, KCI, MiMedix, RedDress, Systagenix; Consultant Arthrocare, Cytomedix, EnzySurge, KCI, Mego-Aflec, MiMedix, MxBiodevices, Smith & Nephew, Scientific advisor MoMelan, Systagenix, Tissue Therapies Brand names are included in this presentation for participant clarification purposes only. No product promotion should be inferred. Accreditation In support of improving patient care, North American Center for Continuing Medical Education, LLC (NACCME) is accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team. CME NACCME designates this live activity for a maximum of 1 AMA PRA Category 1 Credit. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Accreditation (continued) CNE This continuing nursing education activity awards 1.0 contact hour. Provider approved by the California Board of Registered Nursing, Provider #13255 for 1.0 contact hour. CPME North American Center for Continuing Medical Education, LLC (NACCME) is approved by the Council on Podiatric Medical Education as a sponsor of continuing education in podiatric medicine. This program is approved for 1.0 continuing education contact hour or 0.1 CEU. Instructions for Receiving Documentation of Credit To be eligible for credit, participants must attend the full activity and complete the evaluation following the educational session Participants who complete the evaluation online at will immediately receive documentation of credit Participants who submit a hard copy evaluation will receive documentation of credit within 8 weeks.

2 Learning Objectives Describe intrinsic and extrinsic factors that can impair wound healing such as growth factors, ischemia, infection, and arterial insufficiency Discuss the role of wound bed preparation prior to the application of advanced wound care therapies Assess the impact of topical wound treatment solutions on the infected wound Evaluate the evidence to support the use of acellular human dermal matrices for patients with chronic wounds. Review the history and efficacy of suction blister epidermal grafting and explore challenging cases in which suction blister epidermal grafting has been used successfully Wound Reconstruction and the Role of Advanced Technologies Charles Andersen, MD, FACS Vascular/Endovascular/Limb Preservation Surgery Service Wound Care Clinic, Madigan Army Medical Center Wound Management The persistence of a chronic wound increases the risk for severe adverse events (infection, osteomyelitis, amputation, and death) and has a significant impact on the well being of the patient and the healthcare budget Rapid reconstruction of tissue defects restores function and helps prevent amputations Reconstruction of complex tissue defects is a pathway that may involve multiple modalities (multimodal therapy) to include NPWT, dermal matrix products, STSG or flaps, and complex reconstructive surgery. Components of a Successful Wound Care Program A successful wound care program requires a systemic, integrated multidisciplinary approach Wound care education requires an organized approach it is more than just knowing what products are available Developed a model utilizing the advanced trauma life support (ATLS) approach NPWT = negative pressure wound therapy; STSG = split thickness skin graft. Snyder RJ, et al. Ostomy Wound Manage. 2010;56(4 Suppl):S1-24. ATLS = advanced trauma life support. Systemic, Integrated Approach to Wound Care Assessment: Primary assessment: Wound characteristics and etiology Secondary assessment: Evaluation of all systemic factors that can have a negative impact on wound healing Primary Assessment: Identify and Treat the Etiology Failure to identify and correct the etiology of a wound can lead to failure to heal or a recurrence Neuropathic diabetic ulcers: Failure to off-load will delay or prevent healing or lead to an early recurrence Venous leg ulcers: Failure to use compression will delay or prevent healing or lead to an early recurrence Van Rijswijk L, et al. Wound Assessment and Documentation. In: Krasner D, et. al Chronic Wound Care Armstrong DG, et al. Diabetes Care. 2001;24(6):

3 Secondary Assessment Not just about products, it is about a systemic approach to the patient and the wound Many times the wound is a manifestation of a chronic illness (cancer, poor cardiac function) Example: poor nutrition in a diabetic patient 50% ICU patients are malnourished Secondary assessment the identification and management of negative healing factors Secondary Assessment: Negative Healing Factors Infection Foreign body and/or devitalized tissue Edema or venous insufficiency Medications: antiinflammatory, ace inhibitors, calcium channel blockers Arterial insufficiency: hypoxia ICU = intensive care unit. Saltzman E, et al. Malnutrition in the Intensive Care Unit. In: Nutritional Considerations in the ICU: Science, Rationale and Practice Negative Healing Factors (continued) Smoking It is not just about the hole in the patient, but the whole patient Multidisciplinary Approach Repeated trauma or pressure Malnutrition Many patients with chronic wounds are very sick patients that require intense medical management, as well as wound care Anemia Deficiencies in vitamins or minerals Tumors Metabolic factors Diabetes, hyperglycemia It is about the details Failure to Progress Wound Management Repeat the primary and secondary assessment Change in philosophy Often times the wound care product is not the problem, but the lack of recognition and treatment of the etiology or recognition and correction of systemic patient factors is the problem Old focus Heal the wound New focus Reconstruct of tissue defects to restore the highest level of function in the shortest time possible with the lowest incidence of recurrence Reconstruction is a pathway utilizing multiple tools Roukis TS, et al. Foot Ankle Spec. 2010;3(4):

4 Reconstructive Pathway Debridement 3 steps Getting the wound ready, reconstructing the tissue defect, and covering the wound Removal of callus and necrotic tissue Wound bed preparation (getting the wound ready) Decreasing the bacterial burden Debridement Advanced wound care including NPWT with or without instillation therapy Wound reconstruction Removal of phenotypically altered cells: the cellular burden Biologics Wound coverage Living cell therapy STSG or flap Epidermal harvesting and grafting Bacterial Bioburden Problematic? metabolic load by bacteria in wound bed Produces endotoxins and proteases Stimulates a proinflammatory wound environment Physical Barrier In chronic wounds, dead tissue is unreceptive to growth factors or any bioactive treatment Once the wound is debrided and bleeding, growth factors are stimulated and microhealing can begin Wounds do not heal Necrotic tissue acts as a physical barrier for growth factorreceptor interaction Andersen A, et al. J Wound Care. 2007;16(4): DFU Time to Healing vs Serial Debridement Mulder GD, et al. J Am Podiatr Med Assoc. 2002;92(1): Wound Bed Preparation Following debridement, NPWT can be utilized for wound bed preparation Serial debridement centers healed 29% of patients compared with 15% at nonserial debridement centers DFU = diabetic foot ulcer. Cardinal M, et al. Wound Repair Regen. 2009;17(3): NPWT may be utilized alone NPWT may be utilized with irrigation

5 Irrigation vs Instillation NPWTi System Irrigation Washing or flushing a wound with a stream of liquid Instillation Introducing a liquid to a wound and allowing the liquid to remain for a specific period of time before being drained New technology incorporates both NPWT and instillation features, including a volumetric pump and dressings designed for instillation therapy, into one system Instillation helps to further promote wound healing by combining the benefits of irrigation using topical wound solutions with the advantages of NPWT NPWTi = NPWT with instillation. The Playing Field Topical Wound Treatment Solutions Perhaps the most deceptively simple of all therapeutic procedures is the treatment of cutaneous infection with topical medication. Despite the unique accessibility of the skin to scientific investigation, it has for too long been the playground of crude empiricism. John C. Lantis, II, MD Columbia University Selwyn S. Microbial interactions and antibiosis. In: Maibach H, Aly R, eds. Skin microbiology: relevance to clinical infection. New York, NY: Springer-Verlag; 1981: Role of Topical Antimicrobials Many wounds support relatively stable mixed communities of microorganisms, often without signs of infection In chronic wounds, reduction of certain microbial species, such as anaerobic bacteria, to limit undesirable odors Mixed communities of 4 or more bacterial species that impede healing is to be justified The eradication of beta hemolytic streptococci or staphylococci and Pseudomonas before grafting is essential Intervention to prevent the development of systemic infection in critically colonized or locally infected wounds is reasonable Bowler PG, et al. Clin Microbiol Rev. 2001;14(2): Hansson C, et al. Acta Derm Venereol. 1995;75(1): Bowler PG, et al. Wounds. 1999;11: Trengove NJ, et al. J Wound Care. 1996;5(6): Schraibman IG. Ann R Coll Surg Engl. 1990;72(2): Gilliland EL, et al. Ann R Coll Surg Engl. 1988;70(2): Cleanse Wound Gently, Avoid the Use of Abrasive Wipes and Cold Solutions Irrigation: the practice of washing out or flushing a wound or body opening with a stream of a liquid solution High 50 psi (jet) vs low pressure 4 to 15 psi (gravity or bulb syringe) Continuous vs pulsatile Low vs high volume Solution (water, saline, antiseptics, or combinations) Lavage: the process of washing/irrigating out an organ, usually the bladder, bowel, paranasal sinuses, or stomach, for therapeutic purposes with a liquid solution Instillation: a procedure in which a liquid solution is slowly introduced into a cavity or passage of the body and allowed to remain for a specific length of time before being drained or withdrawn Trevelyan J. Nurs Times. 1996;92(16): Fletcher J. Prof Nurse. 1997;12(11): Williams C. Br J Nurs. 1999;8(21): Oliver L. Nurs Stand. 1997;11(20): Davies C. Nurs Times. 1999; 95(43):71-72, 75. Bergstrom N, et al. Treatment of pressure ulcers. Clinical Practice Guideline, No AHCPR Publication No Rockville, MD: U.S. Department of Health and Human Services. Public Health service, Agency for Health Care Policy and Research. Chisholm CD, et al. Ann Emerg Med. 1992;21(11):

6 Choose Dressings that Minimize Trauma/Pain During Application and Removal Treat Infections that May Cause WRP and Inhibit Healing Cadexomer iodine dressings 72-hour wear times Silver-containing foams Minimal pain NPWT with instillation 72-hour wear times Others Maintenance of moist wound healing Atraumatic to the wound and surrounding skin Absorbency capacity (fluid handling/retention capacity) Allergy potential Select dressings that stay in situ for a longer period to avoid frequent removal Schwartz JA, et al. Int Wound J. 2013;10(2): Lantis JC II, et al. J Wound Care. 2011;20(2): Raad W, et al. Int Wound J. 2010;7(2): Cadexomer iodine dressings 1 log reduction in the chronic wound Silver-containing foams 1 log reduction in the chronic wound NPWT with instillation 1 log reduction in the chronic wound Others Level of Bioburden (log10 cfu/g tissue) Patients With Clinical Signs of Infection (%) WRP = wound-related pain. Schwartz J, et al. Int Wound J. 2013;10(2): Baseline Week 8 Assessment 100 Baseline (0) Mean Multiple Results Individual Results Median Time (weeks) Anatomical location Patient positioning Relation to gravity Complexity Tunnel Undermining Infection Hardware Size Areas Volume Others Clinical Considerations Wound Cleansing Choice St. Luke s Roosevelt Hospital, Division of Vascular Surgery Ambulatory DFU: cadexomer/iodine Venous/painful: silver-containing foams Vasculitic painful: silver-containing foams Others: honey-based products (as part of trials) Larger wounds (>40 sq cm?) That can be hospitalized: NPWT with instillation That need quick closure: Pain Other surgery planned Anatomically appropriate Need jump start NPWT with Instillation Protocol St. Luke s Roosevelt Hospital, Division of Vascular Surgery Obtain quantitative culture prior to debridement Debride Pulse irrigate Obtain quantitative culture postdebridement Use NPWT with instillation place directly in the operating room Change 2 to 3 times in 7-day treatment course 10-minute soak followed by 50-minute NPWT to 3.5-hour NPWT Quarter strength Dakin s solution How Do We Do This? Algorithm Decide size of the foam L x W x D (2 cm) x.20 cc Decide what solution Dakin s 0.125?? Decide the time to dwell Many factors We are doing 10-minute dwell/50-minute NPWT Have moved to 10-minute dwell/3.5-hour NPWT

7 Clinical Questions What agents? Different bacteria different choices? How long to dwell? Different agent require different dwells Dakin s very reactive, short dwell PHMB minimum 20-minute dwell How long to provide negative pressure? What potentiates macro and micro deformation? PHMB = polyhexamethylene biguanide. In Vitro Biofilm Data NPWT with Instillation of the Appropriate Solution May Control Bacteria Known to Form Biofilm Mature biofilm starts to form within 4 to 10 hours, providing a window of opportunity during biofilm development where biofilm can be disrupted Immature biofilms were exposed to antimicrobial solutions 0.1% PHMB 5% mafenide acetate 0.004% sodium hypochlorite % hypochlorous acid Intermittent exposure of developing biofilm to antimicrobial solutions reduced the number of mature biofilm bacteria by 1 to 2 log CFU Average CFU/mL 1.00E E E E E E E E E E+00 Control Saline 0.1% Polyhaxanide CFU = colony-forming unit. Cowan L, Philips P, Stechmiller J, et al. Antibiofilm Strategies and Antiseptics. In: Willy C, ed. Antiseptics in Surgery Update Berlin, Germany: Lundqvist Books; % 0.004% Mafenide Sodium Acetate Hypochlorite % Hypochlorous Acid In Vitro Biofilm Data NPWT with Instillation of the Appropriate Solution May Control Bacteria Known to Form Biofilm Sodium Hypochlorite Solutions In vitro biofilm model using pig skin Instilled 6 times in 24 hours with 10-minute soak time using V.A.C. Instill wound therapy Solutions used 0.9% sodium chloride (normal saline) 0.1% polyhexamethylene biguanide (PHMB or polyhexanide) Instillation therapy with antimicrobial solutions reduced biofilm bacteria by 3 log CFU 1.00E E E E E E E E E+00 Untreated V.A.C. Therapy Cowan L, Philips P, Stechmiller J, et al. Antibiofilm Strategies and Antiseptics. In: Willy C, ed. Antiseptics in Surgery Update Berlin, Germany: Lundqvist Books; Average CFU/mL V.A.C. VeraFlo Therapy With Normal Saline V.A.C. VeraFlo Therapy With 0.1% PHMB Device class Antimicrobial Agent Commercially available names Dakin s, Dermacyn, Microcyn FDA cleared for topical application? Yes FDA indication Wound cleansing Common available forms Solution available in variety concentrations 0.5% (full strength), 0.25% (half strength), and 0.125% (quarter strength) Common irrigation concentrations (%) Concentration commonly used 0.025% or 0.125%; NPWT instillation recommended Concentration max is 0.125% (quarter strength) Common clinical usage Useful against nonsystemic infections due to drug-resistant microorganisms Gerit D, et al. Wounds. 2007;19(7): PHMB Solutions Summary Device class Wound cleanser Commercially available name Prontosan FDA cleared for topical application? Yes FDA indication Intended for cleaning wounds and for moistening and lubricating absorbent wound dressings for ulcers, burns, postsurgical wounds, and abrasions Common available forms 0.1% solution Common irrigation concentrations (%) 0.1% solution Common clinical usage Aids in the removal of dirt and debris from chronic wounds, skin ulcers, and abrasions, even when surfaces are difficult to access, such as skin folds, fissures, and wound pockets Gerit D, et al. Wounds. 2007;19(7): We assume most chronic wounds are infected/critically colonized Minor colonizations can be treated with debridement; then Topical antimicrobial Major colonizations can be treated with debridement; then Irrigation and NPWT

8 The Repair Process Is Based on Inflammation and Leads to Scar Formation Acellular Human Dermal Matrix for Chronic Wounds Fibrin scaffold Inflammation and proliferation Fibrosis and remodeling to scar Alexander Reyzelman, DPM California School of Podiatric Medicine at Samuel Merritt University Regeneration May Be Enabled Using Biologic Scaffolds Tissue contains the perfect scaffold for supporting the regenerative process Scar: When an injury occurs, the body s first reaction is hemostasis when fibrin and inflammatory cytokines form a blood clot or provisional scaffold More inflammatory cells arrive remodeling the clot into a scar Repair Regenerative Tissue Scaffolds Cellular Repopulation Removing the scaffold from tissue without damage allows integration into the body Matrix damage triggers inflammation (and resorption or encapsulation) Regenerated tissue: process of allowing nature to follow its own regenerative process restoring tissue to its original structural, functional, and physiological condition Revascularization Transition to Functional Host Tissue Harper J, et al. Wounds. 2007;19(6): The ECM Contains Complex 3-Dimensional Information Native collagen and key matrix components Fibrillar collagens and collagen VI Elastin Hyaluronan Matrix capable of supporting cell migration and capillary invasion (no abnormal cross-links) Rich in proteoglycans Large and small Proteoglycans Fibronectin Vascular Channels ECM = extracellular matrix. Harper J, et al. Wounds. 2007;19(6): Initial biomechanics that support suture retention and high load Preparation Process Remove cells and end up with an acellular scaffold Cells are removed to prevent rejection Maintain biochemical components so that the patient s immune system responds to it as normal tissue Scaffold has architectural and biochemical parameters that the patient s cells can recognize the tissue as being normal

9 Animal Studies Have Shown That Acellular Regenerative Tissue Scaffolds Are Not Adhesiogenic* Cross-Linked Porcine ADM Is More Fibrogenic against Healthy Bowel than Noncross-Linked Dermal Matrix Plast. Reconstr. Surg. 114:464, 2004 Plast. Reconstr. Surg. 125:167, 2010 Cross-Linked PADM *Correlation of these results to results in humans have not been established. Butler CE, et al. Plast Reconstr Surg. 2004;114(2): Burns NK, et al. Plast Reconstr Surg. 2010;125(1): Comparison of Full-Thickness DFU Prospective, Randomized, Controlled Trials Pivotal Study Study End Point Clinical Effectiveness of an Acellular Dermal Regenerative Tissue Matrix Compared with Standard Wound Management in Healing DFUs: A Prospective, Randomized, Multicenter Study % of Average Time to # of Wounds Complete Applications Healed Healing Reyzelman, et al 12 weeks 1 70% 5.7 weeks Veves, et al 12 weeks % 9.3 weeks Marston, et al 12 weeks 8 30% Not Reported Noncross-Linked ADM = acellular dermal matrix; PADM = porcine acellular dermal matrix. Butler CE, et al. J Am Coll Surg. 2010;211(3): Patients in Study N = 86 Study Group = 47 Received a single application of 4X4 cm human acellular regenerative tissue matrix Control = 39 Received standard-of-care wound management consisting of moist wound therapy with alginates, foams, hydrocolloids, or hydrogels. Primary End Point: Proportion of ulcers that completely healed at 12 weeks (complete healing defined as 100% epithelialization) Secondary End Point: Mean time to healing Reyzelman A, et al. Int Wound J. 2009;6(3): Veves A, et al. Diabetes Care. 2001;24(2): Marston WA, et al. Diabetes Care. 2003; 26(6): Reyzelman A, et al. Int J Wound. 2009;6(3): Clinical Effectiveness of an Acellular Dermal Regenerative Tissue Matrix Compared with Standard Wound Management in Healing DFUs: A Prospective, Randomized, Multicenter Study (continued) Demographic Variable Majority were patients with type 2 diabetes Age (years) Mean Median SD Range Number of patients Obese Body mass index (lbs/in²) Mean Median SD Range Number of patients Diabetes mellitus type Type 1 Type 2 Number of patients SD = standard deviation. Reyzelman A, et al. Int J Wound. 2009;6(3): Study Group (n=46) Comparison of Index Ulcer Location between Treatment Groups Control Group (n-39) Mean Pretreatment Ulcer Duration: ~23 Weeks Most Common Ulcer Area: Foot (10.9%) 41 (89.1%) 46 2 (5.1%) 37 (94.9%) % Number of Patients Mean age: years Demographics 32.6% Acellular Matrix Moist Wound Therapy 32.6% % 12.8% Pretreatment Ulcer Duration (weeks) Study Group (n=46) Control Group (n=39) Mean Median Standard Deviation % 5 8.7% 7.7% Range 0 Toe Foot Heel Other Wound Location Reyzelman A, et al. Int J Wound. 2009;6(3):

10 Surgical Preparation of Wound Site Followed by Randomization into 1 of 2 Groups Study Group (n = 47) Single application of acellular dermal regenerative matrix for wounds (fenestrated) scaffold regenerative tissue matrix 4x4 applied Secured via suture or staple Silver-based nonadherent dressing applied Secondary dressings (hydrogel bolsters or moist gauze) were applied routinely at the rate determined by the investigator until complete epithelialization was achieved or 12 weeks of care Reyzelman A, et al. Int J Wound. 2009;6(3): Control Group (n = 39) Received standard of wound care Moist wound therapy with alginates, foams, hydrocolloids or hydrogels at discretion of treating physician Alginates with foam typically used for heavily exudative wounds Hydrocolloids or hydrogels typically used for minimal exudating wounds Dressing changed daily unless recommended otherwise by treating physician Survival Probability Survivorship Analysis to Complete Healing Product Limit Survival Function Estimates AM ACM SOC + Standard of care Time to Healing (weeks) AM = acellular matrix; CI = confidence interval. Reyzelman A, et al. Int J Wound. 2009;6(3): P = % of AM patients healed by 12 weeks 46% of standard of care patients healed by 12 weeks No. of Subjects Event Censored Median Survival (95% CI) AM 46 70% (32) 30% (14) 7.00 ( ) Standard of care 39 46% (18) 54% (21) (9.00-NA) + + Healing Proportion* Proportion of Healed Ulcers at Weekly Evaluation Intervals Patients that Completely Healed the Mean Time to Complete Healing AM Therapy Moist Wound Therapy 15% Higher vs Control Time to Healing (weeks) AM SOC P =.0289 AM group = 5.7 weeks Control group = 6.8 weeks Proportion of healed ulcers between groups was statistically significant Summary Efficacy for AM demonstrated in UT Grade 1 and 2 diabetic foot ulcers 70% of AM patients completely healed Healed patients reached 100% epithelialization in 5.7 weeks (mean closure) Human acellular regenerative tissue scaffolds provide an effective treatment option for diabetic lower extremity wounds in a single application *Proportion of patients who completely healed as defined as 100% epithelialization. Reyzelman A, et al. Int J Wound. 2009;6(3): UT = University of Texas Classification System. Reyzelman A, Crews RT, Moore JC, et al. Int Wound J. 2009;6: Conclusion Results from 97 Wounds The AM is a viable treatment option for the treatment of lower extremity diabetic wounds A multicenter prospective study is underway to further validate the safety and efficacy of the AM 97 wounds from 71 patients 33 females (46.5%) 38 males (53.5%) Mean age: 62.2 ( ) Mean wound age is 18.6 weeks Patient Comorbidities Osteomyelitis 37.1% Obesity 52.0% UT Classification 1B = 1 1A = 15 1C = 0 1D = 2 3D = 33 2A = 18 3C = 3 2B = 8 3B = 7 3A = 3 2C = 4 2D = 3 Infection 54.6% Peripheral Vascular Disease Cardiac Disease Neuropathy 81.4% 86.8% 87.6% Percent Population (%) Winters CL, et al. Adv Skin Wound Care. 2008;21(8):

11 Results* Results Time to Graft Incorporation (weeks) Mean ± SD Median Range Time to Graft Incorporation (weeks) Mean ± SD Median Range Study Population (n=97) 1.5 ± ± UT Grade 1 (n=18) 1.5 ± ± UT Grade 3 (n=33) 1.6 ± ± UT Grade 3 (n=46) 1.5 ± ± Did Not Heal 9.3% Multiple Graft Applications Required 1% Overall Healing Rate Did Not Heal 9.3% 90.7% 89.7% Wounds Healed with Single Graft Application Time to Graft Incorporation (weeks) Mean ± SD Median Range 13.7 ± ± No significant difference between time to graft incorporation, time to 100% granulation, and time to complete healing and UT classification *Complete healing defined as full epithelialization. SD = standard deviation. Winters CL, et al. Adv Skin Wound Care. 2008;21(8): ± ± Overall graft success rate was 89.7% 1 graft failure-healed 7 weeks post second application Overall wound closure rate was 90.7% (88 of 97) Mean time to heal was 13.7 weeks Complete healing defined as full epithelialization. Winters C, et al. ASWC. 2008;21: SBEG Suction Blister Epidermal Grafting Thomas E. Serena, MD, FACS, FACHM, MAPWCA SerenaGroup First described in 1964: primarily used to treat vitiligo Epidermal harvesting Select donor site (thigh, abdomen ) Prep the site Apply a suction cup apparatus to the skin Application of a vacuum in a sealed environment Await blister formation Transfer the graft to the donor site Secure the graft with a pressure or bolster dressing Leave the dressing in place for sufficient time to permit graft take Recipient site Prepare the site by removing any epidermis present Apply the epidermal grafts Secure as above SBEG = suction blister epidermal grafting. Kiistala U. J Invest Dermatol. 1968;50(2): Epidermal Graft Effectiveness Data SBEG in Vitiligo Biswas A, et al. The micrograft concept for wound healing: strategies and application. J Diabetes Sci Technol. 2010;4(4): Hsieh CS, et al. Five years experience of the modified Meek technique in the management of extensive burns. Burns. 2008;34(3): Ichiki Y, et al. Successful treatment of scleroderma-related cutaneous ulcer with suction blister grafting. Rheumatol Int. 2008;28(3): Costanzo U, et al. Autologous suction blister grafting for chronic leg ulcers. J Eur Acad Dermatol Venereol. 2008;22(1):7-10. Njoo MD, et al. A systematic review of autologous transplantation methods in vitiligo. Arch Dermatol. 1998;134(12): Patel NS, et al. Advanced treatment modalities for vitiligio. Dermatol Surg. 2012;38(3): Li J, et al. Suction blister epidermal grafting using a modified suction method in the treatment of stable vitiligo: a retrospective study. Dermatol Surg. 2011;37(7): Epidermal grafting is 53% effective in the treatment of generalized vitiligo and 91% effective for segmental disease SBEG is an established, effective treatment of resistant and stable vitiligo Njoo MD, et al. Arch Dermatol. 1998;134(12): Gupta S, et al. J Am Acad Dermatol. 2003;49(1):

12 Epidermal Grafting for Chronic Leg Ulcers Study design: Prospective trial evaluating the effectiveness of autologous blister grafting for chronic nonhealing leg ulcers Population: 18 patients with 29 wounds Procedure Wound base had to have at least 50% granulation tissue and free of necrotic tissue Blister raised on the abdomen, excised with a scalpel, and transferred to the ulcers A nonadherent primary dressing followed by a compression wrap were applied Results 89% of the ulcers achieved complete closure in 12 weeks Increased granulation tissue and stimulation of epithelialization from the wound edge observed in nearly every case Conclusion Autologous epidermal grafting is a viable option for chronic leg ulcers Until 2012 Epidermal grafting was considered an effective therapy for hypopigmented skin disorders and chronic wounds Harvesting techniques, however, were cumbersome and required considerable time and skill to perform Costanzo U, et al. J Eur Acad Dermatol Venereol. 2008;22(1):7-10. CelluTome Epidermal Harvesting System Development Epidermal Harvesting System Procedure Port au Prince February 2010 The Wound Clinic at Bernard Mevs Hospital August 2012 Device in Place: Skin Heated to 40 C and Negative Pressure Applied Epidermal Grafts Rising

13 Epidermal Grafts Rising Dividing the Epidermal Grafts Pinch Grafts on Adhesive Foam Donor Sites Placing and Securing the Dressing on the Wound Case Study 1 Graft Take 08/20/ /27/2012

14 Case Study 1 (continued) 09/03/ /05/2012 Complete Closure of the Grafted Site at 4 Weeks with Repigmentation 09/10/ /17/2012 Trauma to the Graft Site at Week 4 Donor Site Compression Wrap STSG STSG are harvested using a dermatome The dermatome can be set to varying thickness Donor site of the STSG can be reharvested important in burn care Donor site leaves permanent scar

15 Case Study 2: Diabetic Heel Ulcer Initial Photo Wound Bed at Day 4 NPWT Therapy in Place Using Tegaderm Film for Microdome Acquisition Days 15 and 18 Post-Grafting 3-Week Follow-Up Postepidermal Graft, NPWT Therapy, and Hyperbaric Oxygen Therapy Case Study 3: Chronic Foot Wound Photo prior to epidermal graft placement

16 Follow-Up Post-Application Follow-Up Follow-Up (continued) Follow-Up (continued) Barriers to STSG Anesthesia is required The patient must go to the operating room Operating room time can be difficult to obtain Referral to surgeon for grafting Patient discomfort at donor site Patient concerns over a second wound Donor site healing Concerns over efficacy not well studied Q&A Session