Peripheral Arterial Disease Admissions

CLI AND PAD ADMISSIONS

Critical Limb Ischemia Outcomes

CLI/PAD predominance in Medicare and Medicaid Population

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

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

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 1999 99:2682-91 Kanno S Circ 1999

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 45-60 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

Patented Bioelectric Signals for Specific Target Proteins* SDF-1 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

BIOELECTRIC STIMULATION FOR NON-HEALING ULCER

Bioelectric Stimulation for Non-Healing Wounds International Wound J 2014

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

Abadi Diabetes Res 2017

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

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

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

AMNIOTIC MEMBRANE FOR WOUND HEALING RESULTS GP 1: GP 2 TREATMENT Control Am Membrane Wound Healing 0/11 14/14 Granulation Tiss 2/11 13/14 Pain Reduction 0/11 13/14 El Hanidy et al Int J Womens’s Health 2016

Amniotic Fluid Membrane for Non-Healing Wounds

BIOELECTRIC STIMULATION FOR NON-HEALING ULCER

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

ADRCs for CLI

ADRCs for CLI PRE ADRCs POST ADRCs

CRITICAL LIMB ISCHEMIA NON-HEALING ULCER

CRITICAL LIMB ISCHEMIA NON-HEALING ULCER

CRITICAL LIMB ISCHEMIA NON-HEALING ULCER

CRITICAL LIMB ISCHEMIA NON-HEALING ULCER