SARMA

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SARMA San Antonio Regenerative Medicine
Association
April 13, 2007
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University of Texas Health Science Center San
Antonio University of Texas at San
Antonio United States Army Institute of
Research Southwest Research Institute Texas
Research Park
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SARMA Agenda13 April 2007

• 900 am - Registration
• 915 am - Welcome / Dr. Steven Wolf
• 930 am - ISR / Dr. Steven Wolf Dr. David Baer
• 950 am - SwRI / Dr. Richard Suzuki
• 1020 am Texas Research Park Foundation / York
  Duncan
• 10 40 am- UTSA / Dr. Anson Ong
• 1110 am - UTHSCSA / Dr. Mary Pat Moyer
• 1130 am Afternoon Agenda / Dr. Mary Pat Moyer
• 1200 - Lunch / Networking
• 100 pm - Charge / Dr. Steven Wolf
• 115 pm - Breakout groups
• 300 pm - Regroup / Outbrief / Summary

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Dr. Steven Wolf, MD USAISR/UTHSCSA
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USAISR
Col John Holcomb
Dr. Basil Pruitt
Col. Charles Wade
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USAISR
Dr. Heather Pidcoke
Dr. Xiaowu Wu
Dr. David Baer
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US ARMY INSTITUTE OF SURGICAL
RESEARCH
Research for the Soldier Combat Casualty Care
Taking Care of the Soldier Trauma, Burn, and
Critical Care
17 November 2006
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BRAC ISR and BAMC CAMPUS
Parking Garage A
Clinical/Admin Addition
Institute of Surgical Research
New ER/ICU Tower
Intrepid Center 2 Fisher Houses
Parking Garage B
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Trauma Critical Care Service

• Level 1 Trauma Center
• 20 Surgical Critical Care Beds (Largest SICU in
  DOD)
• 1,330 Critical Care admissions (Jan - Dec 05)
• 30 Trauma
• 1,210 Trauma admissions (Jan - Dec 05)
• 278 with ISS gt 15
• 85 OIF Trauma patients mostly ortho (Jan - Dec
  05)
• ACS verified - Oct 04 State designated - Mar 06
• Follow-up Civilian Outpatient Visits managed
  through
• Civilian Care Coordination Office (CCCO)

As of 5 Jul 06
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What is a Trauma Registry?

• Demographics
• Injury Patients
• BI and NBI
• Excludes Disease
• Medical/Psychiatric
• Records selected Clinical Parameters
• Resuscitative
• Key Performance Improvement Measures

• Continuum of Care
• IIb, III, IV, V Record
• Coding - ICD-9
• Injury
• Procedures
• Scoring
• Injury (AIS)
• Severity Measures
• Follow Civilian Model
• Est. by OSD(HA) Memo 04-31 dtd 22 DEC 04
• American College of Surgeons

It is not the entire medical record
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Veterinary Support Division

• State of the Art Laboratory Animal Facility
• Secure, climate controlled, AAALAC Accredited
  facility
• Capabilities for housing large small animal
  models
• Comparative pathology facilities
• GLP capable

• Animal Operating Rooms
• 6 operating rooms (ISR/DCI)
• 4 built to human standards to support mass
  casualty
• Animal Intensive Care Unit
• 4 bay animal ICU

• 64 Slice CT Scanner

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Fire Retardant Gloves Make A Difference

• Heat/flash resistant to 800o F
• ALARACT 22 Dec 05 High Incidence of Hand Burns
• Purpose Encourage Soldiers to wear FR gloves

FOUO
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Tissue Engineering for Treatment ofBattlefield
Injuries
Cell-based tissue regeneration - cellular
therapy, that will repair damaged and diseased
tissues by transplanting healthy new cells to the
affected site.  Scaffold-guided tissue
regeneration - porous biodegradable scaffold will
be seeded with donor cells and/or growth factors.
The goal is for the cells to attach to the
scaffold, replicate and ultimately grow into
healthy, functioning tissue as the scaffold
degrades. Bioactive molecule-based tissue
regeneration - utilizing regulatory molecules,
also known as growth factors, cell growth and
differentiation will be induced and directed
within the target tissue.

• Identification of optimal cell sourcesThis
  includes the acquisition of appropriate cells for
  particular applications from a variety of
  potential sources and methods for the directed
  proliferation and differentiation of cells,
  immunological manipulation and the generation of
  genetically engineered cells for in vivo cell
  tracking.
• Development of novel Biomaterials and
  scaffoldsIncludes testing biomaterials that are
  designed to direct the growth, differentiation,
  and organization of cells.
• Functional assessment of regenerated/engineered
  tissuesIncluding mechanical and physiological
  testing and the use of imaging tools for
  real-time, non-destructive, in vitro and in vivo
  assessment of function, efficacy and safety.

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Treatment of Fractures

• Improved local antimicrobial delivery
• Deliver using cement beads - require surgical
  removal
• Bone replacements not requiring removal, speed
  healing, and release antimicrobials
• Acceleration of bone regeneration
• Growth factors as a therapeutic for accelerating
  bone regeneration
• Currently examining selection for best growth
  factors and delivery method
• Congressional and Orthopaedic Trauma Association
  research support
• RFP on website

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Soft Tissue Trauma Care

• Prevention of Infection
• Efforts focused on improved topical agents and
  irrigation protocols
• Technology to visualize bacterial infection
  non-invasively in relevant animal models
• Optimized Use of wound VAC
• Regeneration of Muscle
• Significant morbidity with muscle loss
• Efforts focused on prevention and treatment of
  tourniquet injury
• Future will incorporate traumatic injury and
  regeneration
• Regeneration of Skin
• Engineered skin replacement will significantly
  reduce morbidity and mortality

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ISR Clinical Trials

• Program Objectives
• Observe current combat casualties and those with
  similar civilian injuries for relevant clinical
  problems
• Translate these problems into pre-clinical
  research questions
• Evaluate concepts from successful pre-clinical
  experiments in the clinical arena
• Integrate clinical experimental results with
  training and doctrine for successful translation
  to the battlefield

Combat Casualties
Pre-clinical Research
Clinical Trials
Battlefield Products and Concepts
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ISR Clinical Research Regenerative Medicine

• Acceleration of skin wound healing using ECM
• Regeneration of digit length
• Development of engineered cartilage/chondrocyte
  constructs for ear replacement

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Southwest Research Institute SwRI

• 60 years old
• 1200-acre campus
• 3,000 employees
• 2 million sq. ft. laboratory space
• 455MM revenue in 2006

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Technical Divisions
Aerospace Electronics and Information
Technology Applied Physics Automation and Data
Systems Center for Nuclear Waste Regulatory
Analyses Chemistry and Chemical
Engineering Department of Microencapsulation, Nan
omaterials and Process Engineering Biomedical
Materials Engineering Engine, Emissions, and
Vehicle Research Fuels and Lubricants Research
Mechanical and Materials Engineering Signal
Exploitation and Geolocation Space Science and
Engineering Training, Simulation Performance
Improvement
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SwRI Capabilities
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Steve Wellinghoff, PhDInstitute Scientist

• I am a systems integrator who utilizes multiple
  technologies to make practical devices and
  materials.
• Materials Chemistry, Characterization,
  Processing and Properties
• Ceramic polymer nanocomposites, controlled
  release of biocides, photopolymers, biodegradable
  polymers, corrosion resistant coatings,
  electrochemical based sensors, dental materials,
  and intelligent clothing

stephen.wellinghoff_at_swri.org [phone]
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Neal Vail, PhDPrincipal Engineer

• I use CAE and custom materials to
  microfabricate tissue engineering scaffolds.
• Biomaterials, Ceramics, CAE-Tissue Engineering,
  Encapsulation Drug Delivery, Medical Device
  Development, Molecular Modeling
• Biomaterials engineering with emphasis on bone
  healing and repair, nanoscale materials
  engineering, targeted drug delivery, controlled
  drug release

neal.vail_at_swri.org [phone]
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Richard Suzuki, PhDResearch Engineer

• I examine the interaction of biomaterial
  surfaces with the biological environment to
  better understand the healing process.
• Biomaterials, Surface Modification, Biosensors,
  Tissue Engineering
• Biomaterial inflammatory response, thermally
  controlled hydrophobic surfaces, protein
  separation, interaction of titanium oxides with
  cells

richard.suzuki_at_swri.org [phone]
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Texas Research Park
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Texas Research Park FoundationYork Duncan,
President

• Mission Statement
• To build a world-class center of bioscience
  research, medical education, and job creating
  economic development. The goals are to provide
  healthcare benefits for mankind, to provide
  education for bioscience professionals at the
  graduate level, and to create high-paying jobs in
  a clean industry.

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UTSA
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C. Mauli Agrawal, PhD Biomedical
Engineering Professor and Dean
Bone Tissue Engineering Cartilage
Repair Cardiovascular Tissue Engineering
mauli.agrawal_at_utsa.edu 458-5526
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Joo L Ong Biomedical Engineering
Bone Tissue Engineering Materials In Vitro In
Vivo
anson.ong_at_utsa.edu 458-7149
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Porous Calcium Phosphate Scaffold
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Scaffold Use in Bone Repair
5050 PLA-PGA scaffold (Gel casting technique)
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Scaffolds Used in Articular Cartilage Repair8
week rabbit study
5050 PLA-PGA scaffold (vibrating particle
technique)
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In Vivo Study on Angiogenesis 30,000 Seeded
Incubated for 6 Days pre-implantation Implant
Positioned in Microsurgical Abdominal Pocket
above Omentum
Pre-Implantation
Treated implant with endothelial cells
Post-implantation
Pre-dissection
a
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Dual culture
Gas-plasma treated core with endothelial cells
Ring with osteoblast or precursor cells
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Dr. Hai-Chao HanAssistant Professor
Biomechanics of Arteries and Heart Artery
remodeling Left Ventricular remodeling Tissue
Engineering
hchan_at_utsa.edu (210) 458 4952
Cardiovascular Biomechanics Lab members
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Mechanical Testing to characterize the
mechanical properties of soft tissues
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Lab Organ Culture Techniques
Advantages Ex vivo bench-top system Well-controll
ed environment Maintain whole arteries viable for
up to 2 weeks Applications Bench-top tests for
TE arteries Axial stretch to elongate arteries
Organ culture system
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Dawnlee Roberson, PhDAssistant Professor
I decompose the EMG to determine what is going
on in the neuron, experimentally and modeling.

• Department of Biomedical Engineering
• College of Engineering, UTSA
• Biomechanics/Electrophysiology

Dawnlee.roberson_at_utsa.edu [phone]
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Dawnlee Roberson, PhDAssistant Professor

• Experience/Skills
• Surface and finewire EMG
• Capture electroneurogram
• Modeling
• Strong math background
• Equipment
• Utah electrodes
• Faraday cage
• VICON motion analysis

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Xiaodu Wang Mechanical Engineering
Biomechanics of Bone
xiaodu.wang_at_utsa.edu 458-5565
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Application In situ characterization of bone
formation
Nano testing techniques
Characterization of newly formed bone tissues
Bone Formation
Newly formed bone
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Rena Bizios, PhD
EDUCATION Ph.D. in Biomedical Engineering -
Massachusetts Institute of Technology,
Cambridge, MA M.S. in Chemical Engineering -
California Institute of Technology, Pasadena,
CA B.S. (Cum Laude) in Chemical Engineering -
University of Massachusetts, Amherst, MA
CAREER HIGHLIGHTS Peter T. Flawn Professor at
UTSA (2006-present) Society for Biomaterials,
Clemson Award for Contributions to the Scientific
Literature of Biomaterials (1998) Chalmers
Jubileums Professor, Chalmers U of Technology,
Göteborg, Sweden (Fall, 2002) Fellow, American
Institute for Medical and Biological
Engineering International Fellow of Biomaterials
Science and Engineering, International Union of
Societies for Biomaterials Science and
Engineering Fellow, Biomedical Engineering
Society
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Rena Bizios, PhD

• RESEARCH INTERESTS
• Cellular Engineering
• Cell Responses to Select Biophysical Stimuli
  (specifically, sustained and cyclic pressure,
  shear stress, electrical and magnetic stimuli)
• Cell/Material Interactions
• Chemical Modification of Biomaterial Surfaces
• Nanostructured Biomaterials
• Tissue Engineering

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Richard LeBaron Department of Biology
Cell Adhesion Molecules Integrins Proteoglycans M
olecules of the extracellular matrix
Rlebaron_at_utsa.edu 458-5841
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Roles of the Joint-lubricating Molecule
Proteoglycan-4 (Prg4) in the Development of
Degenerative Temporomandibular Joint Disorders
Our hypothesis is that defective Prg4 leads to
inadequate joint lubrication that will result in
degeneration of the temporomandibular joint (TMJ).
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UTHSCSA
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UTHSCSA
Dr. Mary Pat Moyer Surgery Incell Corporation
Dr. Paula K Shireman Surgery Vascular Division
Dr. Ralph Rawls Restorative Dentistry Biomaterials
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UTHSCSA
Dr. Joel Michalek Epidemiology Biostatistics
Dr. Peter Hornsby Physiology
Dr. Linda McManus Pathology
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Others attending, but no personal photos available
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Peter J. Hornsby, PhD Professor of Physiology
The Problem How to perform repeated noninvasive
intravital microscopy in regenerative medicine
experiments?
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Intravital microscopy can be performed on
unanesthetized animal in restraining devices
Mouse in restrainer window fits against flat
upper clear plate of restrainer
Mouse in restrainer in position under
fluorescence microscope
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Procedure
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Demonstration of use of skin/body wall
window Growth of transplanted MDA231 cells
photographed each day via the window Note rapid
growth of cells and extensive growth of blood
vessels
Numbers days since transplant
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Mouse with skin/body wall window sacrificed
after 30 days
Window integrity and skin integrity are good
after 30 days Only a small rim of dead skin is
noted around the edge No infections noted In the
living animal, behavior is relatively unaffected
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Conclusions A skin/body wall window can be used
chronically in mice and can be used for
noninvasive observations of transplanted
cells/tissues on unanesthetized animals. It could
also be used to observe unmodified mouse organs
(kidney, liver, muscle, bone) by intravital
microscopy.
We are interested in collaborations that take
advantage of the model in any area of
regenerative medicine.
Skin/body wall window
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Dr. Mary Pat Moyer
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April 13, 2007 SARMA Meeting Breakout Sessions
Approach

• Set up Teams (3-5) from multiple institutions
• Team features are as follows
• 1. Senior and junior participants
• 2. Multiple institutions represented
• 3. Scribe (summarize discussion)
• 4. Spokesperson
• Teams Meet for 40 minutes Use SWOT Action
  Forms as Worksheets
• Re-Convene Group Team Summaries
• Identify Actions, Assignments Priority

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April 13, 2007 SARMA Meeting Breakout Session
Team Topics

• SWOT Analysis Individuals fill out forms and
  bring to the team discussion
• Proposed Action Items Short-term Low-Hanging
  Fruit
• Proposed Action Items Long-term Filling the
  Gaps

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SWOT ANALYSIS Worksheet
Strengths
Weaknesses
Opportunities
Threats
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Action Items Worksheet
Proposed Action Items Short-term Low-Hanging
Fruit Proposed Action Items Long-term
Filling the Gaps
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CONSENSUS SWOT ANALYSIS Summary
Strengths
Weaknesses
Opportunities
Threats
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Consensus Action Items Worksheet
Proposed Action Items Short-term Low-Hanging
Fruit Proposed Action Items Long-term
Filling the Gaps
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April 13, 2007 SARMA Meeting Consensus and
Summary Taking Action What Next?

• Priority Action Items Short-term Low-Hanging
  Fruit
• Priority Action Items Long-term Filling the
  Gaps
• Volunteer Roles, Assignments, Deliverables

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Fini, and Thank you!

• Todays SARMA Conference
• sponsored
• by
• Department of Surgery
• UTHSCSA
• San Antonio, Texas

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White Paper - SARMA

• Core foundation document
• Vision
• Goal
• Deliverables
• 3 pages
• Focus areas - extremities (muscle, bone, nerve,
  skin, arteries, cartilage)
• Target audience
• UTHSCSA and UTSA VPR
• Future opportunities

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CONSENSUS SWOT ANALYSIS FINAL SUMMARY
STRENGTHS
WEAKNESSES
Biomechanics Imaging Bioreactor
technology Bench-to-bedside (and back) capability
locally Biomaterials Pilot production/planning
for tech transfer
Inflammation No plan/vision Business planning
OPPORTUNITIES
THREATS
High vis patient population Patients willing to
participate Military Affiliation
Other regenerative medicine centers Conflicting
interests within components (aging, cx, diabetes)
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Action Items (short term)

• Salvage/regeneration of complex wounds
• small -gt large -gt human models
• Salvage of digits
• Pixie dust
• Stem cells soft tissue (muscle) or bone
  (scaffold)
• Sustainability of organization
• Capturing core capability
• Specifics Combat Casualty Care Meeting Aug
• SBIRs/STTRs
• Funding opportunity OTRP (May 8)

• Publicity/Public Relations (for ex Forbes
  insert)
• Begin functional collaborations
• Mouse models matrix function Shireman
• Dental research to SA Baer/Rawls/Bizios
• Help w/white paper Robinson/Michalek-Statistics/
  Moyer
• 1 page core capabilities Appendix to white
  paper Baer/ Ong/ Vail/ Hornsby
• 1 page industry support Moyer

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Action Items (Long term)

• Mammals that regenerate limbs (naked mole rats)
• Integrated strategy (hiring talent leads to
  critical mass)
• Clinical trials (orthopedic surgeon
  participation?)
• Future OTRP grants (funding increase?)
• Technology commercialization/transfer
• Business case applications

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Aim/Vision/Goal

• Limb regeneration and salvage
• Muscle
• Bone
• Connective Tissue
• Inflammatory Process/Reaction
• Nervous System

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How to get there?

• Subprograms
• Tissue based
• Functional and testing based
• Approach based
• Integration

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First collaborations

• Muscle/mouse Shireman/Roberson/Wenke

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Seminar Series and Beyond

• Currently biweekly seminar series
• Teleconference as needed
• Central location/time/day established for seminar
  series
• gt Send best availability to Dawnlee Roberson for
  future meetings (time, date, day)
• Next meeting
• Thursday, May 10 at UTSA, 300 PM, BSE 2.102
• Dr. Roberson in charge and will arrange tours of
  UTSA Facilities
• ISR provides speakers
• Volunteer for presentations in advance

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Immediate Personal actions/role

• White Paper
• Stephen Wolf Committee Head
• Dawnlee Roberson Coordinator
• Susan Robinson - Coordinator
• Joel Michalek Statistical Core Information
• Mary Pat Moyer Industry Support
• Institutional Representatives
• To provide 1 page core capabilities for
  Appendix to White Paper
• David Baer Joo Ong
• Neil Vail Peter Hornsby

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Attendees
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(No Transcript)
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SWOT Results

• Strengths
• Biomechanics
• Imaging
• Bioreactor technology
• Bench-to-bedside (and back) capability locally
• Biomaterials
• Pilot production/planning for tech transfer
• Weaknesses
• Inflammation
• No plan/vision
• Business planning
• Opportunities
• High vis patient population
• Patients willing to participate
• Threats
• Other regen medicine centers
• Conflicting interests within components (aging,
  cx, diabetes)