3. Peripheral Arterial Disease Admissions

4. CLI AND PAD ADMISSIONS

5. Critical Limb Ischemia Outcomes

6. CLI/PAD predominance in Medicare and Medicaid Population

9. TREATMENT OPTIONS FOR PAD/CLI
SURGICAL REVASCULARIZATION
CATHETER-BASED REVASCULARIZATION
BIOELECTRIC STIMULATION
STEM CELLS
AMNIOTIC FLUID AND MEMBRANE
GENE PLASMIDS

10. Bioelectric stimulation to Enhance Angiogenesis
I. Isolated skeletal muscle cells
Stimulated using the precise signal for VEGF
Confirmed increase VEGF mRNA in medium
Resulted in enhanced Endothelial cell activatioin
II. Animal Model of hind limb ischemia*
Bioelectric stimulation too low to cause muscle contraction or discomfort
Induced demonstrable increase in blood flow and VEGF expression in the muscle.
Simple and effective strategy to enhance expression of targeted proteins in the target tissue
*Kanno et al Circulation 1999

11. VEGF mRNA Expression increased 480 % in Skeletal Muscle
Increase in Capillary Density and VEGF Expression with Bioelectric Stimulation
230 % Increase
P< 0.01
VEGF mRNA Expression increased 480 % in Skeletal Muscle
Kanno S. Circ :
Kanno S Circ 1999

12. BIOELETRIC STIMULATION FOR NON-HEALING WOUNDS DUE TO CLI
Czech Republic
41 Patients with diabetes and non-healing leg or foot ulcers of various etiologies; arterial or venous, or pressure; all had std wound care
Bioelectric stimulation for minutes, 3 x’s/week for 8 weeks using 1.5 uA with cutaneous patch electrodes-induced no reported discomfort
Over 90% Reduction in Wound Size by 8 weeks of this treatment.
Wirsing et al internatl Wound J 2013

13. Patented Bioelectric Signals for Specific Target Proteins*
SDF Stem Cell Differentiating Signal
VEGF Tropoelastin
PDGF Activin A&B
IGF Follistatin
HGF eNOS
EGF HIF-1 alpha
Confirmed Expression in multiple tissues
ONLY STRATEGY THAT STIMULATES
HOMING/DIFFERENTIATION/PROLIFERATION

14. BIOELECTRIC STIMULATION FOR NON-HEALING ULCER

16. Bioelectric Stimulation for Non-Healing Wounds
International Wound J 2014

17. BIOELETRIC STIMULATION FOR NON-HEALING DIABETIC FOOT ULCERS
30 Patients with wound ulcers unresponsive to all conventional therapies
Randomized, single blind, placebo control trial
Bioelectric stimulation: On or Off
1 hr sessions, 3 x’s/week, for 4 weeks (12 total)
60 % Reduction in Wound Area, vs 20% Control
Wound fluid after 1 treatment showed significant increase in HIF-1 alpha levels p=0.01 vs Control
Also significant increase VEGF with wound healing
Asadi et al Diabetes Res 2017

18. Abadi Diabetes Res 2017

19. Amniotic Fluid and Membrane
Fluid that bathes the fetus
Readily available at C-Section deliveries
Microarray analysis: 240 proteins-pro-regenerative and pro-angiogenic
Membrane (chorion:amnion) lines uterine cavity
Membrane Can be lipholized and shipped that can be used to cover the ulcer/wound, various sizes
Now being used for burns and other wounds

20. AMNIOTIC MEMBRANE FOR WOUND HEALING
RANDOMIZED TRIAL OF 25 PATIENTS WITH
NON-HEALING LEG ULCERS
Goal: Could Am Membrane promote wound healing and reconstruction vs scarring and fibrosis
GP 1: STANDARD CARE/DAILIY DRESSING CHANGE
GP 2: TOPICAL COVERING OF ULCER WITH AMNIOITIC MEMBRANE + DAILY DRESSING CHANGE
Follow Up at Day 7, 14, 21, 30, 45, and 60
Assessed rate and amount of wound healing, ulcer depth, and self-assessed pain
El Hanidy et al Int J Womens’s Health 2016

21. AMNIOTIC MEMBRANE FOR WOUND HEALING
RESULTS
GP 1:
NO IMPROVEMENT IN WOUND HEALING
ONLY 18% SHOWED ANY GRANULATION TISSUE
NO IMPROVEMENT IN PAIN
GP 2:
ALL 14 PATIENTS HAD TOTAL WOUND HEALING WITHIN AVG 33 DAYS OF TREATMENT
13/14 HAD HEALTHY GRANULATION TISSUE
79% HAD SIGNIFICANT REDUCTION IN PAIN
El Hanidy et al Int J Womens’s Health 2016

22. AMNIOTIC MEMBRANE FOR WOUND HEALING
RESULTS
GP 1: GP 2
TREATMENT Control Am Membrane
Wound Healing / /14
Granulation Tiss / /14
Pain Reduction / /14
El Hanidy et al Int J Womens’s Health 2016

23. Amniotic Fluid Membrane for Non-Healing Wounds

24. BIOELECTRIC STIMULATION FOR NON-HEALING ULCER

25. ADIPOSE DERIVED REGEN CELLS FOR CHRONIC LIMB ISCHEMIA
16 patients with CLI facing amputation
ADRCs injected Intramuscularly along calf
No complications of cell delivery
RESULTS: 12/16 were spared amputation
Very impressive wound healing
Significant increase in blood flow by Angiogram
Vaclav Prochazka Chech Repbulic

26. ADRCs for CLI

27. ADRCs for CLI
PRE ADRCs
POST ADRCs

28. CRITICAL LIMB ISCHEMIA NON-HEALING ULCER

29. CRITICAL LIMB ISCHEMIA NON-HEALING ULCER

30. CRITICAL LIMB ISCHEMIA NON-HEALING ULCER

31. CRITICAL LIMB ISCHEMIA NON-HEALING ULCER