Shock Wave Therapy for Soft Tissue Wounds: Phase II ... · Bioelectric dressing Microelectric...
Transcript of Shock Wave Therapy for Soft Tissue Wounds: Phase II ... · Bioelectric dressing Microelectric...
The views expressed in this presentation are
those of the presenter, and do not reflect the
official policy of the;
- Trideum Corporation
- Department of Defense, or
- United States Government
Disclaimer
Financial Disclosure
No financial interest or investment in the technologies presented
- In 1676, observed bacteria and other microorganisms using a single-
lens microscope he designed.
- Shocking discovery at that time. Things living inside humans!!!
Replica of one of his microscopes
Anton van Leeuwenhoek
Scientific Bias Disclosure
· What’s your story? What excites you? How did you get to where you are
today?
· What research/work do you conduct?
· What STEM skills and knowledge do you actively need to be successful in
your job?
· What courses or extracurricular activities have helped you in your career?
· What guidance would you provide to students to prepare them to enter the
workforce and manage challenges they may encounter?
· Do you offer any resources to support teachers or outreach programs for
students and teachers to explore your research area or STEM field?
My Story
Mina Izadjoo, PhD
Chief Science Officer
Trideum Biosciences
Trideum Biosciences
We conduct test and evaluation of therapeutics and devices
Troubleshoot and recommend path to advance new technologies
Success Track record
2017 Innovation in North America Award
Gold Award for Excellence - Best Poster
2016 Military Health Systems
Research Symposium (MHSRS)
2016 "Best Poster Award” at the 5th
World Union of Wound Healing
Societies (WUWHS) conference in Florence, Italy
Where are we Located?
Trideum Biosciences laboratories are located in Frederick, MD near Fort Detrick
Trideum Biosciences is an associate company with the Hudson Alpha Institute of Biotechnology in Huntsville near the Trideum Corporation headquarter office.
www.trideumbiosciences.com [email protected]
Who are Our People?
VP & Chief Science Officer - Dr. Mina Izadjoo
◦ Ph.D., Microbiology and Immunology, LSU
◦ Former Director of Diagnostics & Translational
Research Center for the Henry M. Jackson Foundation for Advancement of Military Medicine
◦ Former Division Chief of Wound Biology & Translational Research, Armed Forces Institute of Pathology
◦ Associate Professorship at Uniformed Services University for Health Sciences (USUHS)
◦ President Emeritus of the Washington Academy of Sciences
Advancing medical products in support of Armed Forces
Armed Forces Institute of Pathology Walter Reed Army Medical Center
Walter Reed National Military Medical
Center
Uniformed Services University of the
Health Sciences (USU)
Humans and Microorganisms………….
Bacteria: Friends or Foes?
We are outnumbered by our bacterial tenants.
We provide them room and board and in return they help us with digestion,
vitamin production and innate immune response.
Microbial World: A Challenging Frontier
The physical diversity of microorganism is a reflection of underlying
genetic differences.
http://textbookofbacteriology.net
Bacteria could have traveled through
space on comets. If even one microbe
survived space travel to Earth, it would be
enough to start a colony on our planet. Courtesy of NASA
Air Force Proficiency Testing Program
7900 Fast Real Time PCR
ABI 7500 Fast DX
Swine Flu Pandemic
Conversion of Drug-Resistant Infectious Agents to
Drug Sensitivity
Conversion
by EGS Antibiotic
Resistant
Bacteria
Strains
Antibiotic
Sensitive
Bacteria
Strains
Dr. Sidney Altman
-This is a 14 year-old girl who presented with symptoms of a space occupying
lesion in the posterior fossa consistent with a brain tumor.
Diagnosis: Medulloblastoma
Helicobacter pylori bacteria in the stomach has been linked to ulcers
and stomach cancers.
SPL / BARCROFT MEDIA
Association of Wound Healing and Cancer
J Wound Care. 2014 Jun;23(6):314, 316-9.
Wound infections and healing: are they contributing factors for
carcinogenesis? Park S, M. Izadjoo.
Prostate cancer cells, after
interacting with normal wound
healing cells have become more
invasive and more able to
metastasize.
Tumor cells secrete signals that call in
wound healing cells to the tumor site. In
the process, the normal wound healing
cells make the tumor cells more
aggressive and able to metastasize.
http://www.ns.umich.edu/new/
21432
Combat Casualty in Recent Conflicts in Iraq and Afghanistan
News Story (Wednesday, August 12, 2009)
AFIP Partners With Walter Reed to Help Advance
Combat Wound Care Program
Human Skin
Skin is the interface between human body and the
environment, prevents loss of moisture, blocks
entry of pathogens and foreign material.
The skin microbiome may have beneficial or
detrimental effects on wound healing.
Skin generates microcurrents
Wound Healing: Complex and Dynamic Process
http://en.wikipedia.org/wiki/Wound_healing#mediaviewer/File:Wound
_healing_phases.png
• Normal wound healing is a well-coordinated and progressive series of
events designed to restore the barrier function and mechanical integrity of
the skin.
• Wound healing involves interactions between cells and their
microenvironment.
• Traditional Wound Care (Wound-closure Products; Tissue Adhesives,
Sealants, and Glues; Fibrin-based Sealants; Collagen-based Sealants;
Synthetic Adhesives/Glues; Anti-infective Dressings)
• Basic Wound Care (Tapes; Dry Dressings; Cleansing)
• Advanced Wound Care (Films; Foam Dressings; Collagen; Alginates;
Hydrocolloids; Hydrogels; Super Absorbers)
• Bio-Active Wound Care (Artificial Skin and Skin Substitutes)
• Therapy Devices (Negative Pressure Wound Therapy Devices; Pressure
Relief Devices; Electrical Stimulation Devices; Ultra-Violet Devices;
Oxygen and Hyperbaric Oxygen Equipment; Whirlpool Therapy Devices;
Electromagnetic Therapy Devices; Ultrasound Devices).
Wound Care Products
$15.6 billion (2014) 18.3 billion (2019)
http://www.marketsandmarkets.com/Market-Reports/wound-care-market-371.html
The use of silver as an antimicrobial for infection spans hundreds of
years. The ancient Greeks and Romans used silver to disinfect their
water and food supplies.
Silver: An age-old treatment modality in modern times (Surg Nurs. 2010 Apr-Jun;30(2):90-3)
• Silver was also used in ancient times to treat burns and wounds as a
wound dressing.
• Silver solutions were approved by FDA in the 1920s.
Procellera Technology Microcurrent generating antimicrobial wound dressing
wireless
microcell
batteries Silver
In presence of a conductive fluid (i.e. saline, hydrogel, wound exudate) batteries are activated and generate microcurrents
Zinc
Inspired by the Body
Electricity is Essential to Wound Healing
An electric potential exists across intact skin.
The body naturally creates and uses electrical energy to promote healing.
When skin is wounded, a change in electric
potential occurs. This stimulus is the earliest
guidance signal to initiate cell migration and
re-epithelialization, and is essential to wound
healing.
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
Log
(No
. of
viab
le c
ells
/ml)
Wound isolates
Initial (CFU/mL) After (CFU/mL)
Figure 1. Antibacterial properties of the wound dressing showing reduction of bacteria after 24 hours exposure against clinical wound isolates.
ground
Positive
Bioelectric dressing
Microelectric Measurement System Set Up
Microelectric potential can be
measured by moving the positive
probe on the wetted dressing with
fluids (culture medium, bacteria
cultures and saline). During
measurement, the ground probe
stayed on the white place.
Bacterial Biofilm is a major barrier to wound healing
• Complex microbial communities
• Microbial community produce and secrete a protective surrounding substance that
allows it to stick to surfaces, living or non living.
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
Log
(No
. of
viab
le c
ells
/ml)
Wound isolates
Initial (CFU/mL) After (CFU/mL)
Figure 1. Antibacterial properties of the wound dressing showing reduction of bacteria after 24 hours exposure against clinical wound isolates.
• Biofilms are everywhere and it is a tragedy to use clinical microbiology
techniques for their identification. The clinical microbiology is for floating
bacteria.
• We need other methodologies for detection and treating biofilm diseases.
• Patent: Device and Methods for Creating and Testing Biofilms (Application
# 62075343)
Planktonic vs Biofilm
Efficacy Testing of Procellera against A. baumannii biofilm
1. Add 1 mL A. baumannii biofilm and swill the culture onto a TSA plate (Fig. 1A & 2A)
2. Place Procellera directly onto the biofilm and incubate at 37°C for 24 h (Fig. 1B & 2B)
3. Check a bacterial growth (Fig. 1C & 2C)
Bacteria killed
1A
1B 1C
2A
2B 2C
Biofilm of Acinetobacter baumannii on a Poloxamer
hydrogel plate
1 day-old A. baumannii
onto a 20% Poloxamer hydrogel
plate
4 day-old A. baumannii
onto a 20% Poloxamer hydrogel
plate
1 day-old A. baumannii
onto a TSA plate
All plates were incubated at 37°C, 48 h
Procellera + incubation at 37°C, 24 h
There was no significant bacterial growth.
Bacterial cultures are mixed with 30% poloxamer hydrogels in
Mueller-Hinton broth (MHB). Mono-species biofilms were formed in
poloxamer hydrogels placed onto glass coverslips (JWC in press).
A
B
D
C
A new poloxamer biofilm model
Anti-Biofilm Efficacy using Drip-Flow Reactor (DFR)
Acinetobacter
baumannii
Pseudomonas
aeruginosa
blank Procellera Procellera
Fig. 2. Formation of A. baumannii and P. aeruginosa biofilms on the sample dressings of blank and
Procellera in colony DFR biofilm model (A). Microscopic observations of A. baumannii and P.
aeruginosa biofilms stained by crystal violet in colony DFR (B).
A B
blank
Procellera
Procellera
Patent: Device and Methods for Creating and Testing
Biofilms (Application # 62075343)
A new platform technology for standardized biofilm
formation and testing.
Wound infections are commonly polymicrobial and interspecies interactions
play a significant role in wound infections.
S. aureus is commonly isolated from wound infections and has become an
alarming problem due to emergence of several methicillin-resistant strains
(MRSA).
More than 90% of all S. aureus isolates from human infections are gold
pigmented.
Golden pigment is the manifestation of staphyloxanthin biosysnthesis, a
virulence factor to survive stressful environment.
P. aeruginosa is often isolated along with S. aureus from wound infections.
Wound Microbiome Communications
Pseudomonas aeruginosa induced pigment production and
enhanced virulence in a white phenotypic variant of
Staphylococcus aureus
We isolated two pigment variants of S. aureus and one strain of P.
aeruginosa from the same clinical sample of a patient with soft tissue
wound.
S. aureus variants produced white and yellow colonies.
We demonstrated that white variant can be triggered to produce golden
pigment by the P. aeruginosa isolate.
Effect of co-culture with different bacteria on
pigment production by the S. aureus white variant
Control W
+
E. coli
W
+
Acinetobacter
W
+
Enterobacter
W
+
P. aeruginosa
• Medical community is beginning to recognize the significance of
polymicrobial infections and many therapies are now take into
account the polymicrobial nature of wound infections.
• At present, it is impossible to define the role of each participating
bacterium in these communities and the wound outcome.
• It is critical to understand the interaction between bacterial species in
wound.
Importance of Understanding Microbiome Communications
Biofilm Therapeutics
Serum Wound Effluent Urine
Bioflux 200
Cellular adhesion at
2 hours and 6 hours
under shear flow.
Efficacy of novel antibacterial agents for
treating polymicrobial wound infections
Distinctive stages and strain variation of A. baumannii biofilm development
2-D 3-D
A. baumannii isolates from human wounds showed attachment occurred
at the moment of contact. The first report to show the effectiveness of
this organism in attaining irreversible attachment.
Feng et al JWC 2013, 22(4): 1-9
Clinical Evaluation of a Bioelectric Dressing System for
Acute Wound Management
Wound Healing Assessment
Martin Army Community Hospital
A critical project addressing joint force health protection capability.
Team Effort
Application of a Novel Cold Atmospheric
Plasma for Water Decontamination
Plasma: Fourth State of Matter
The three known states of matter are solids, liquids and gases. Plasma is the
fourth state of matter.
Plasma make 99 percent of the known universe. Plasmas are formed when
atoms are stripped of their electrons, producing ionized gas flows.
Plasma does not contain molecules. It is a gas that is composed of ions.
Technology Description
Cold Plasma
Cold Plasma Device
This pocket-size cold plasma technology is the next generation technology due to its
size, portability, precision, reduced cost and ease of application with no requirement
for any noble gas. Ideal device for field application.
Cold Plasma Application
Medical equipment sterilization
Food decontamination
Antimicrobial device
Decontaminated military gear
Protective shield around sensitive electronic
devices
Stealth technology
Nuclear/chemical detection
Biosensors/Biosignature
Medicinal/Healthcare Application is relatively
young (15 yrs)
Efficacy against Pseudomonas aeruginosa, A Bacterial Pathogen
Efficacy against Trichophyton rubrum
A Toe Fungal Pathogen
B C D A
Treatment with Cold Plasma No Treatment
Microbial Biofilms
A major medical, industry and environmental
problem
TESTING FOUNDATIONS FOR BUSINESS APPLICATIONS
A NEW STANDARD FOR ANTIMICROBIAL AND ANTI-BIOFILM
TESTING
Biofilms
• Complex microbial communities
• Microbial community produce and secrete a protective surrounding substance
that allows it to stick to surfaces, living or non living.
Next Steps……………….
Manufacture, Validate, Market
Human Microbiome………
There are 100 trillion bacterial cells living with each one of us.
This is ten times the number of our own cells.
We need to find out how microorganisms contribute to health and disease.
Human DNA is only a small fraction of the genetic
material in our bodies.
New Frontiers
Role of Women in Advancement of Military Medicine
Women in Warfare and the Military
The second-century carving
two female gladiators (Ancient
Era)
522 BC: Leutenant Artunis,
Commander of Persian Army,
daughter of Artebaz, Sepahbod of
Darius the Great.
A woman using a compass to measure
distances on a diagram (c. 1310 AD)
Women and Science
1775 - 1783
Women served traditional roles within the U.S. Army
such as cooks, laundresses, nurses and seamstresses.
During the American Revolution some women served in
combat alongside their husbands or disguised as men.
There were some courageous women took on roles as
spies.
Deborah Sampson (1760 - 1827)
She had a desire to join the Continental Army.
First enlisted as Timothy Thayer and then Robert Shurtleff (1782).
She wrote to her family that was working in “ a large but well regulated family”.
Augusta Ada Byron Lovelace (1815-1852)
Computer Scientist
The world’s first computer programmer; the
programming language “Ada” was named
in her honor.
Maria Mitchell (1818-1889)
Astronomer
In 1847, her discovery of a comet invisible
to the naked eye won her international
fame and a medal from the king of
Denmark.
Florence Bascom (1862-1945)
Geologist
She was the first women and first geologist
to be awarded a Ph.D. from Johns Hopkins
University.
Maria Sklodowska Curie (1867-1934)
Physicist and Chemist
Dr. Elizabeth Blackwell (1821-1910)
First Female to receive a medical
degree in US.
Dr. Mary Edwards Walker (1832-
1919)
First Female surgeon
First Female US Army Surgeon
(1863)
1970: Women never made up more than 6% of any medical school in
US.
Rebecca Lee Crumpler
First African-American women to
receive an MD (1864)
Eliza Ann Grier, (ex-slave) the first
African-American women licensed
to practice medicine (1898).
Clara Barton (1821 – 1912)
Founder and the First President of the American Red Cross
Floreance Sabin, the first female
faculty of Johns Hopkins School of
Medicine (1903).
“A pioneer for women in science”
Margaret Craighill, the
first woman MD to join
US military (1943)
1972: Congress passes the Higher Education Act prohibiting any sex
discrimination in educational institutional that receive federal funds.
Lt. Gen. Patricia D.
Horoho became the first
female and first nurse to
become surgeon
general of the Army
Dec. 7, 2011.
Maj. Gen Marcia M.
Anderson became the
Army's first-ever female
African-American officer to
obtain the rank of major
general in Oct. 1, 2011.
U.S. Army female soldiers in Boldak
district in Afghanistan's Kandahar
province (2013).
Deborah Sampson
(1760 - 1827)
Nancy Grace Roman, Margaret Hamilton, Sally Ride, and Mae Jemison
“ It is not the strongest of the species that
survive, nor the most intelligent, but the
one most responsive to change.”
Adapt to Change
The past is connected to the present and to the future through
knowledge and challenges faced by mankind.