Update in Wound Management: New Technology Options In Managing Chronic Wounds

1. Update in Wound Management: New Technology Options In Managing Chronic Wounds S. Kwon Lee, MD FACS FCCWS

2. MIST Therapy® SystemTherapeutic Ultrasound MIST Therapy Is Different From Other Ultrasound Devices

3. MIST THERAPY IS AN EVIDENCE BASED ADVANCED MODALITY THAT: • Promotes Wound Healing • Promotes New Cell Growth • Removes Bacteria • Cleans & Debrides • Painless

4. Promotes Wound Healing “The MIST Therapy System produces a low-frequency, ultrasound-generated mist used to promote wound healing through wound cleansing and maintenance debridement by the removal of yellow slough, fibrin, tissue exudates, and bacteria.”

5. APWT Promotes New Cell Growth MIST Therapy is a healing device for wounds and uses acoustic pressure to stimulate new cell growth. The cell walls of healthy human tissue cells, when put under stress will proliferate at a much faster rate. Studies show that when the acoustic pressure from MIST Therapy hits healthy cells, they become elongated and deform, causing a greater mitotic response of new healthy cells.

6. Removes Bacteria “Mist Therapy also uses acoustic pressure to remove bacteria. Unlike healthy tissue cells, the cell walls of bacteria are hard, like egg shells, and studies have shown that bacteria cells break apart and are destroyed when the acoustic pressure from a MIST Therapy treatment comes in contact with them.”

7. Cleans & Debrides “Although not a primary debridement tool, MIST Therapy helps to remove yellow slough, fibrin, necrotic tissue, and bacteria. This is especially helpful and beneficial in the removal of biofilm that often “stalls” the healing process in wounds.”

8. Painless “Since MIST Therapy is a noncontact and a nonthermal ultrasound device, it is also a painless procedure. It is one of one six products and one of only three devices cleared by the FDA allowed to say in its clearance statement that it promotes wound healing.”

9. MIST Therapy® SystemProduct Description MIST Therapy System Components Generator & Transducer Generator MIST Therapy System Transducer 9 ML-66103_A 4/2/07

10. MIST Therapy® SystemProduct Description MIST Therapy Applicator Kit Components Applicator & Sterile Saline (100 ml) Chux Pad & Anti-Microbial Wipes Applicator Kit Applicator, Saline, Chux Pad, Wipes 10 ML-66103_A 4/2/07

11. MIST Therapy is Easy to Use Easy Set Up Assemble saline bottle & applicator onto transducer Select treatment time & begin treating the wound Short Treatment Time Average of 5 minutes Range of 3-20 minutes Minimum Treatments of 3 times per week Easy Clean Up Discard applicator, saline bottle, and chux pad Wipe transducer & generator with anti-microbial wipes MIST Therapy® SystemProduct Description 11 ML-66103_A 4/2/07

12. MIST Therapy System FDA Clearance 510(k) Clearance June 2005 “The MIST Therapy System produces a low frequency ultrasound-generated mist used to promote wound healing through wound cleansing and maintenance debridement by the removal of yellow slough, fibrin, tissue exudates and bacteria” MIST Therapy® SystemFDA Clearance and Indications for Use 12 ML-66103_A 4/2/07

13. MIST Therapy® SystemFDA Clearance and Indications for Use The MIST Therapy System FDA Clearance is Not Wound Specific 13 ML-66103_A 4/2/07

14. Contraindications Do not use near electronic implants / prosthesis Near or over the heart or over the thoracic area if the patient is using a cardiac pacemaker On the lower back during pregnancy or over a pregnant uterus Over areas of malignancies MIST Therapy® SystemProduct Description 14 ML-66103_A 4/2/07

15. MIST Therapy® SystemGeneral Therapeutic Ultrasound This drawing depicts the effects of low frequency, non-contact, non-thermal ultrasound on human fibroblasts • Please note the cavitation on and near the cell surface • Please note the acoustic microstreaming along the cell surface 15 The mechanism of action of MIST Therapy has not been established in clinical trials. This is an illustration only. This drawing is meant to illustrate the concepts of cavitation and acoustic microstreaming. ML-66103_A 4/2/07

16. Randomized Clinical Trials Efficacy of MIST Therapy for the Treatment of Diabetic Foot Ulcers. Dr. Ennis Efficacy of MIST Therapy for the Treatment of Non-Healing Leg and Foot Ulcers Associated with Limb Ischemia. Dr. Kavros Observational Registries Effectiveness of MIST Therapy in Chronic Foot and Leg Ulcerations. Dr. Kavros Effectiveness of MIST Therapy for the Healing of Chronic Wounds. Dr. Ennis Evaluate the effectiveness of MIST Therapy System with Illinois Healthcare and Family Services Cellular Stimulation Studies Physiological Effects of Ultrasound MIST Therapy on Fibroblasts. Dr. Lei Effects of MIST Therapy on Fibroblastic Migration Rates. T. Conner-Kerr Bacteria Reduction Studies Effects of MIST Therapy on Bacterial Levels in a Chronic Wound Bed. Dr. Kavros Effects of MIST Therapy on Common Bacterial Wound Pathogens. Dr. Kavros MIST Therapy® SystemEvidence-Based Wound Care Growing Body of Evidence 16 ML-66103_A 4/2/07

17. Evidence-Based Leadership Celleration conducted this study to provide wound care professionals the data needed to make evidence-based treatment decisions Outcomes Significant Benefit with use of MIST Therapy compared to the sham control 40.7% v. 14.3% at 12 weeks, p = 0.036 Published in a Peer-Reviewed Journal Ostomy / Wound Management, 2005; 51 (8) 24-39 MIST Therapy® SystemEvidence-Based Wound Care Randomized, Multi-Center, Double-Blind, Sham Controlled Clinical Trial Primary Endpoint • Complete Wound Healing (without Drainage) in Diabetic Foot Ulcers Principal Investigator • Dr. William Ennis Study Design • The vascular status was standardized • Off-loading was requested with fixed ankle walkers and diabetic socks were provided • Patients required to ambulate 75% of time • Both groups received the same moist wound healing dressing protocol 17 ML-66103_A 4/2/07

18. MIST Therapy® SystemEvidence-Based Wound Care Significant Benefit with MIST Therapy Complete Wound Closure Without Drainage P = 0.036 40.7% 14.3% 18 Ultrasound Therapy for Recalcitrant Diabetic Foot Ulcers: A randomized, double blinded, sham-controlled, multi-center study - Ostomy/Wound Management , 2005;51(8)24-39 ML-66103_A 4/2/07

19. Primary Purpose of the Study Investigate the Effect of MIST Therapy on Non-Healing Leg and Foot Ulcers Associated with Chronic Critical Limb Ischemia Principal Investigator Dr. Steven Kavros Study Location Mayo Clinic, Rochester, Minnesota Study Design Prospective, randomized, parallel controlled study Control Arm received Mayo Clinic SOC MIST Therapy with Mayo Clinic SOC All patients had to have CCLI End Point, 50% or greater in wound healing in 12 weeks Assess predictive value of TcPO2 in wound healing with MIST Therapy MIST Therapy® SystemEvidence-Based Wound Care Randomized Clinical Trial Outcomes • MIST Therapy with SOC gave 63% vs. 29% (p<0.001) in 50% or greater in wound healing • Failure to achieve 50% or greater was 37% vs. 71% in MIST/SOC arms • Predictive value of TcPO2 demonstrates trend in non-healing wounds in CCLI Accepted for Publication • Advances in Skin and Wound Care, December, 2006 19 ML-66103_A 4/2/07

20. MIST Therapy® SystemEvidence-Based Wound Care Mayo Clinic Study: Limb Ischemia and MIST Therapy (12 week outcome) 63% 29% 20 ML-66103_A 4/2/07

21. Results of Fibroblast Study #1 Cellular Stimulation Fibroblasts migrate 30-35% faster T. Conner-Kerr, Ph.D, PT. CWS, East Carolina University, Greenville, NC Results of Fibroblast Study #2 Cellular Stimulation Growth factor release, TGFb & KGF ERK/JNK ratios support cellular repair J. Lai, DPM & M. Pittelkow, MD, Department of Dermatology, Mayo Clinic MIST Therapy® SystemEvidence-Based Wound Care 21 ML-66103_A 4/2/07

22. MIST Therapy® SystemEvidence-Based Wound Care Control (2 minutes, 30 seconds of treatment with saline) Staphylococcus aureus MIST Therapy (2 minutes, 30 seconds of treatment with saline and low frequency non contact ultrasound) SEM* TEM† 22 * SEM (scanning electron microscopy) † TEM (transmission electron microscopy) ML-66103_A 4/1/07

23. MIST Therapy® SystemEvidence-Based Wound Care Control (2 minutes, 30 seconds of treatment with saline) MRSA (Methicillin-resistant Staphylococcus aureus) MIST Therapy (2 minutes, 30 seconds of treatment with saline and low frequency non contact ultrasound) SEM TEM 23 * SEM (scanning electron microscopy) † TEM (transmission electron microscopy) ML-66103_A 4/1/07

24. MIST Therapy® SystemEvidence-Based Wound Care Control (2 minutes, 30 seconds of treatment with saline) Pseudomonas aeruginosa MIST Therapy (2 minutes, 30 seconds of treatment with saline and low frequency non contact ultrasound) SEM TEM 24 * SEM (scanning electron microscopy) † TEM (transmission electron microscopy) ML-66103_A 4/1/07

25. MIST Therapy® SystemEvidence-Based Wound Care Control (2 minutes, 30 seconds of treatment with saline) VRE (Vancomycin-Resistant Enterococcus) MIST Therapy (2 minutes, 30 seconds of treatment with saline and low frequency non contact ultrasound) SEM TEM 25 * SEM (scanning electron microscopy) † TEM (transmission electron microscopy) ML-66103_A 4/1/07

26. And Celleration is Just Getting Started … Bacteria Characterization Studies Multi-Center Human Bacteria Reduction Study Midwestern University – Bacterial Effects Mayo Clinic – Biofilm Effects MIST Therapy® SystemEvidence-Based Wound Care 26 ML-66103_A 4/2/07

27. L Buttock/Hip 7/27

28. L Buttock/Hip 8/4

29. L Buttock/Hip 8/28

30. R Ankle 8/21

31. R Ankle 9/6

32. Sacral 7/18

33. Sacral 8/7

34. Summary • MIST is a Proven Healing Device • Heals Wounds Faster • Growing Body of Evidence • Randomized Clinical Trials • Observational Registries • Published in Peer-Reviewed Journals • Cellular Stimulation • Bacterial Reduction • Cleans, Debrides & Preps Wound Bed • Easy to Use • Economics are Compelling