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

Faculty

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

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

•  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

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 www.naccme.com/program/2013-527-3 will immediately receive documentation of credit

•  Participants who submit a hard copy evaluation will receive documentation of credit within 8 weeks.

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.

NPWT = negative pressure wound therapy; STSG = split thickness skin graft. Snyder RJ, et al. Ostomy Wound Manage. 2010;56(4 Suppl):S1-24.

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

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. 2007. Armstrong DG, et al. Diabetes Care. 2001;24(6):1019-1022.

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

ICU = intensive care unit. Saltzman E, et al. Malnutrition in the Intensive Care Unit. In: Nutritional Considerations in the ICU: Science, Rationale and Practice. 2002.

Secondary Assessment: Negative Healing Factors

•  Infection

•  Foreign body and/or devitalized tissue

•  Edema or venous insufficiency

•  Medications: anti-inflammatory, ace inhibitors, calcium channel blockers

•  Arterial insufficiency: hypoxia

•  Smoking

Negative Healing Factors (continued)

•  Repeated trauma or pressure

•  Malnutrition

•  Anemia

•  Deficiencies in vitamins or minerals

•  Tumors

•  Metabolic factors

•  Diabetes, hyperglycemia

Multidisciplinary Approach

Many patients with chronic wounds are very sick patients that require

intense medical management, as well as

wound care

“It is not just about the hole in the patient, but the whole patient”

“It is about the details”

Failure to Progress

•  Repeat the primary and secondary assessment

•  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

Wound Management

•  Change in philosophy

•  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):177-183.

Reconstructive Pathway

•  3 steps – Getting the wound ready, reconstructing the tissue defect, and covering the wound

•  Wound bed preparation (getting the wound ready)

–  Debridement

–  Advanced wound care including NPWT with or without instillation therapy

•  Wound reconstruction

•  Biologics

•  Wound coverage

–  Living cell therapy

–  STSG or flap

–  Epidermal harvesting and grafting

Removal of callus and necrotic tissue

Decreasing the bacterial burden

Removal of phenotypically altered

cells: the cellular burden

Debridement

Bacterial Bioburden Problematic?

•  ↑ metabolic load by bacteria in wound bed

•  Produces endotoxins and proteases

•  Stimulates a proinflammatory wound environment

•  Wounds do not heal

Andersen A, et al. J Wound Care. 2007;16(4):171-175.

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

Necrotic tissue acts as a physical barrier

for growth factor-receptor interaction

Mulder GD, et al. J Am Podiatr Med Assoc. 2002;92(1):34-37.

DFU Time to Healing vs Serial Debridement

DFU = diabetic foot ulcer. Cardinal M, et al. Wound Repair Regen. 2009;17(3):306-311.

Serial debridement centers healed 29% of patients

compared with 15% at nonserial debridement centers

Wound Bed Preparation

•  Following debridement, NPWT can be utilized for wound bed preparation

•  NPWT may be utilized alone

•  NPWT may be utilized with irrigation

Irrigation vs Instillation

•  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 System

NPWTi = NPWT with instillation.

Topical Wound Treatment Solutions

John C. Lantis, II, MD Columbia University

The Playing Field

“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.”

Selwyn S. Microbial interactions and antibiosis. In: Maibach H, Aly R, eds. Skin microbiology: relevance to clinical infection. New York, NY: Springer-Verlag; 1981:63-74.

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): 244-269. Hansson C, et al. Acta Derm Venereol. 1995;75(1):24-30. Bowler PG, et al. Wounds. 1999;11:72-78. Trengove NJ, et al. J Wound Care. 1996;5(6):277-80. Schraibman IG. Ann R Coll Surg Engl. 1990;72(2):123-124. Gilliland EL, et al. Ann R Coll Surg Engl. 1988;70(2):105-108.

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):46-48. Fletcher J. Prof Nurse. 1997;12(11):793-796. Williams C. Br J Nurs. 1999;8(21):1460-1462. Oliver L. Nurs Stand. 1997;11(20):47-56. Davies C. Nurs Times. 1999; 95(43):71-72, 75. Bergstrom N, et al. Treatment of pressure ulcers. Clinical Practice Guideline, No. 15. 1994. AHCPR Publication No. 95-0652. 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):1364-1367.

Choose Dressings that Minimize Trauma/Pain During Application and Removal

•  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):193-199. Lantis JC II, et al. J Wound Care. 2011;20(2): 90-96. Raad W, et al. Int Wound J. 2010;7(2):81-85.

Treat Infections that May Cause WRP and Inhibit Healing

•  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

Individual Results Multiple Results Mean

7 6

4

0

2

Leve

l of B

iobu

rden

(lo

g10

cfu/

g tis

sue)

Baseline Week 8 Assessment

100

80

40

0

20

Patie

nts

With

Clin

ical

Si

gns

of In

fect

ion

(%)

Baseline (0)

4 2 Time (weeks)

8 12

WRP = wound-related pain. Schwartz J, et al. Int Wound J. 2013;10(2):193-199.

60

5

3

1

100

83

55

42 33

Median

Clinical Considerations

•  Anatomical location •  Patient positioning •  Relation to gravity •  Complexity

–  Tunnel

–  Undermining

•  Infection •  Hardware

–  Size

–  Areas

•  Volume •  Others

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

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 + 0.003% hypochlorous acid

•  Intermittent exposure of developing biofilm to antimicrobial solutions reduced the number of mature biofilm bacteria by 1 to 2 log CFU

Control Saline 0.1% Poly-

haxanide

5% Mafenide Acetate

0.004% Sodium Hypo-

chlorite + 0.003%

Hypochlorous Acid

1.00E+08

1.00E+07

1.00E+09

1.00E+06

1.00E+05

1.00E+04

1.00E+03

1.00E+02

1.00E+00

1.00E+01

Aver

age

CFU

/mL

CFU = colony-forming unit. Cowan L, Philips P, Stechmiller J, et al. Antibiofilm Strategies and Antiseptics. In: Willy C, ed. Antiseptics in Surgery Update 2013. Berlin, Germany: Lundqvist Books; 23-30.

In Vitro Biofilm Data NPWT with Instillation of the Appropriate Solution

May Control Bacteria Known to Form Biofilm

•  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

Untreated V.A.C.® Therapy

V.A.C. VeraFlo™ Therapy

With 0.1%

PHMB

V.A.C. VeraFlo™ Therapy

With Normal Saline

1.00E+07

1.00E+08

1.00E+06

1.00E+05

1.00E+04

1.00E+03

1.00E+02

1.00E+00

1.00E+01

Aver

age

CFU

/mL

Cowan L, Philips P, Stechmiller J, et al. Antibiofilm Strategies and Antiseptics. In: Willy C, ed. Antiseptics in Surgery Update 2013. Berlin, Germany: Lundqvist Books; 23-30.

Sodium Hypochlorite Solutions

•  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):173-182.

PHMB Solutions

•  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):173-182.

Summary

•  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

Acellular Human Dermal Matrix for Chronic Wounds

Alexander Reyzelman, DPM California School of Podiatric Medicine at

Samuel Merritt University

The “Repair” Process Is Based on Inflammation and Leads to Scar Formation

Fibrin scaffold

Fibrosis and

remodeling to scar

Repair

Inflammation and

proliferation

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

Regeneration May Be Enabled Using Biologic Scaffolds

•  Tissue contains the perfect scaffold for supporting the regenerative process

•  Removing the scaffold from tissue without damage allows integration into the body

•  Matrix damage triggers inflammation (and resorption or encapsulation)

Harper J, et al. Wounds. 2007;19(6):163-168.

Regenerated tissue: process of allowing nature to follow its own regenerative process—restoring tissue to its original structural, functional, and

physiological condition

Regenerative Tissue Scaffolds

Cellular Repopulation

Revascularization

Transition to Functional Host Tissue

The ECM Contains Complex 3-Dimensional Information

•  Native collagen and key matrix components

•  Matrix capable of supporting cell migration and capillary invasion (no abnormal cross-links)

•  Rich in proteoglycans

•  Initial biomechanics that support suture retention and high load

ECM = extracellular matrix. Harper J, et al. Wounds. 2007;19(6):163-168.

Fibrillar collagens and collagen VI

Hyaluronan

Large and small Proteoglycans

Fibronectin Vascular Channels

Elastin

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

Animal Studies Have Shown That Acellular Regenerative Tissue Scaffolds Are Not Adhesiogenic*

Plast. Reconstr. Surg. 114:464, 2004

Plast. Reconstr. Surg. 125:167, 2010

*Correlation of these results to results in humans have not been established. Butler CE, et al. Plast Reconstr Surg. 2004;114(2):464-473. Burns NK, et al. Plast Reconstr Surg. 2010;125(1):167-176.

Cross-Linked Porcine ADM Is More Fibrogenic against Healthy Bowel than Noncross-Linked Dermal Matrix

ADM = acellular dermal matrix; PADM = porcine acellular dermal matrix. Butler CE, et al. J Am Coll Surg. 2010;211(3):368-76..

Cross-Linked PADM Noncross-Linked

Comparison of Full-Thickness DFU Prospective, Randomized, Controlled Trials

Pivotal Study Study End Point

# of Applications

% of Wounds Healed

Average Time to Complete Healing

Reyzelman, et al 12 weeks 1 70% 5.7 weeks

Veves, et al 12 weeks 3.9 56% 9.3 weeks

Marston, et al 12 weeks 8 30% Not Reported

Reyzelman A, et al. Int Wound J. 2009;6(3):196-208. Veves A, et al. Diabetes Care. 2001;24(2):290-295. Marston WA, et al. Diabetes Care. 2003; 26(6):1701-1705.

Clinical Effectiveness of an Acellular Dermal Regenerative Tissue Matrix Compared with Standard Wound Management in Healing

DFUs: A Prospective, Randomized, Multicenter Study

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 J Wound. 2009;6(3):196-208.

SD = standard deviation. Reyzelman A, et al. Int J Wound. 2009;6(3):196-208.

Clinical Effectiveness of an Acellular Dermal Regenerative Tissue Matrix Compared with Standard Wound Management in Healing

DFUs: A Prospective, Randomized, Multicenter Study (continued)

•  Mean age: 55-59 years

•  Majority were patients with type 2 diabetes

•  Obese

Demographic Variable Study Group (n=46)

Control Group (n-39)

Age (years) Mean Median SD Range Number of patients

55.4 55.0 9.6

32-78 46

58.9 58.0 11.6

35-93 39

Body mass index (lbs/in²) Mean Median SD Range Number of patients

33.1 32.1 6.7

24.3-52.8 45

34.6 33.5 8.5

20.9-61.1 38

Diabetes mellitus type Type 1 Type 2 Number of patients

5 (10.9%)

41 (89.1%) 46

2 (5.1%)

37 (94.9%) 39

Most Common Ulcer Area: Foot

Comparison of Index Ulcer Location between Treatment Groups

Pretreatment Ulcer Duration (weeks)

Study Group (n=46)

Control Group (n=39)

Mean 23.3 22.9

Median 16.0 12.0

Standard Deviation 22.4 29.8

Range 0.00-96.00 3.00-139.00

Mean Pretreatment Ulcer Duration:

~23 Weeks

Reyzelman A, et al. Int J Wound. 2009;6(3):196-208.

Demographics

0

5

10

15

20

Foot Heel

Wound Location Toe Other

Num

ber o

f Pat

ient

s Moist Wound Therapy

Acellular Matrix 32.6%

12.8%

32.6%

43.6%

8.7%

20.5%

10.9%

7.7%

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

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

Reyzelman A, et al. Int J Wound. 2009;6(3):196-208.

Survivorship Analysis to Complete Healing

AM = acellular matrix; CI = confidence interval. Reyzelman A, et al. Int J Wound. 2009;6(3):196-208.

0

0.2

0.4

0.6

1.0

0 2 5 10 12

Time to Healing (weeks) 1 3 7 11 9

Surv

ival

Pro

babi

lity 0.8

6 4 8

Standard of care

AM

P = .0075

Product Limit Survival Function Estimates

70% of AM patients healed by 12 weeks

46% of standard of care patients healed by 12 weeks

+ + +

+

+

+ + +

+

+ +

ACM

SOC

No. of Subjects Event Censored Median Survival (95% CI)

AM 46 70% (32) 30% (14) 7.00 (4.00-11.00)

Standard of care 39 46% (18) 54% (21) 12.00 (9.00-NA)

*Proportion of patients who completely healed as defined as 100% epithelialization. Reyzelman A, et al. Int J Wound. 2009;6(3):196-208.

Proportion of Healed Ulcers at Weekly Evaluation Intervals

0

0.1

0.2

0.4

0.6

0.8

0 2 5 10 12

Time to Healing (weeks) 1 3 7 11 9

Hea

ling

Prop

ortio

n*

0.3

0.5

0.7

6 4 8

Moist Wound Therapy

AM Therapy

15% Higher vs

Control

AM

SOC

P = .0289

AM group = 5.7 weeks

Control group = 6.8 weeks

Proportion of healed ulcers between groups was statistically significant

Patients that Completely Healed the Mean Time to Complete Healing

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

UT = University of Texas Classification System. Reyzelman A, Crews RT, Moore JC, et al. Int Wound J. 2009;6:196-208.

Conclusion

•  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

Results from 97 Wounds

•  97 wounds from 71 patients

•  33 females (46.5%)

•  38 males (53.5%)

•  Mean age: 62.2 (40.0-85.9)

•  Mean wound age is 18.6 weeks

Winters CL, et al. Adv Skin Wound Care. 2008;21(8):375-381.

1B = 1 1C = 0 1D = 2

2B = 8

2C = 4 2D = 3

3B = 7

3C = 3

3A = 3

UT Classification

1A = 15

3D = 33

2A = 18

Patient Comorbidities

Neuropathy

Cardiac Disease

Peripheral Vascular Disease

Infection

Obesity

Osteomyelitis

0 20 60 70 100

Percent Population (%) 10 30 40 90 80 50

87.6%

86.8%

81.4%

54.6%

52.0%

37.1%

Results*

•  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):375-381.

Study Population

(n=97)

UT Grade 1 (n=18)

UT Grade 3 (n=33)

UT Grade 3 (n=46)

Time to Graft Incorporation (weeks) Mean ± SD Median Range

1.5 ± 0.90

1.3 0.43 − 4.4

1.5 ± 0.55

2.0 0.71 − 2.0

1.6 ± 0.90

1.3 0.57 − 3.0

1.5 ± 1.0

1.1 0.43 − 4.4

Time to Graft Incorporation (weeks) Mean ± SD Median Range

5.0 ± 3.5

4.0 0.43 − 16.7

4.4 ± 2.1

4.0 1.4 − 8.0

5.3 ± 3.8

4.0 0.71 − 16.7

5.1 ± 3.8

3.6 0.43 − 14.9

Time to Graft Incorporation (weeks) Mean ± SD Median Range

13.7 ± 9.0

10.9 1.7 − 57.6

10.8 ± 3.2

9.5 5.0 − 17.0

12.3 ± 7.0

10.0 1.7 − 29.7

16.4 ± 11.5

13.9 4.7 − 57.6

Results

•  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;21:375-81.

Wounds Healed with Single Graft

Application

Overall Healing Rate

Did Not Heal 9.3% Did Not Heal 9.3% Multiple

Graft Applications Required 1%

90.7% 89.7%

Suction Blister Epidermal Grafting

Thomas E. Serena, MD, FACS, FACHM, MAPWCA SerenaGroup™

SBEG

•  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):129-137.

Epidermal Graft Effectiveness Data

•  Biswas A, et al. The micrograft concept for wound healing: strategies and application. J Diabetes Sci Technol. 2010;4(4):808-819.

•  Hsieh CS, et al. Five years’ experience of the modified Meek technique in the management of extensive burns. Burns. 2008;34(3):350-354.

•  Ichiki Y, et al. Successful treatment of scleroderma-related cutaneous ulcer with suction blister grafting. Rheumatol Int. 2008;28(3):299-301.

•  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):1543-1549.

•  Patel NS, et al. Advanced treatment modalities for vitiligio. Dermatol Surg. 2012;38(3):381-391.

•  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):999-1006.

SBEG in Vitiligo

•  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):1543-1549. Gupta S, et al. J Am Acad Dermatol. 2003;49(1):99-104.

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

Costanzo U, et al. J Eur Acad Dermatol Venereol. 2008;22(1):7-10.

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

CelluTome™ Epidermal Harvesting System Development

The Wound Clinic at Bernard Mevs Hospital

August 2012

Port au Prince February 2010

Epidermal Harvesting System Procedure

Device in Place: Skin Heated to 40°C and Negative Pressure Applied Epidermal Grafts Rising

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

08/20/2012 08/27/2012

Graft Take

Case Study 1 (continued)

09/03/2012 09/05/2012

Complete Closure of the Grafted Site at 4 Weeks with Repigmentation

09/10/2012 09/17/2012

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

Case Study 2: Diabetic Heel Ulcer

Initial Photo NPWT Therapy in Place

Wound Bed at Day 4

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

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