DTIC ADA536112: Armed Forces Institute of Regenerative Medicine Annual Report 2010

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Armed Forces
Institute of
Regenerative
Medicine
Annual Report 2010
our science for their healing
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Armed Forces Institute of Regenerative Medicine Annual Medicine 2010
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Armed Forces Institute of Regenerative Medicine

Annual Report 2010

Mr. Terry Irgens

AFIRM Director

[email protected]
our science for their healing
our science for their healing
Executive Summary ................................................................................................................................................................................................ vii

I: Introduction

Background ........................................................................................................................................................................................................1

Research Goals .................................................................................................................................................................................................2

History ...............................................................................................................................................................................................................4

Funding – A Six-Way Partnership ......................................................................................................................................................................4

Structure ............................................................................................................................................................................................................5

Management and Oversight ..............................................................................................................................................................................7

II: Limb and Digit Salvage
Background ........................................................................................................................................................................................................9

Unmet Needs ...................................................................................................................................................................................................10

Areas of Emphasis ...........................................................................................................................................................................................11

Bone Repair and Regeneration ...................................................................................................................................................................12

Soft Tissue Repair and Regeneration (excluding nerve) .............................................................................................................................14

Nerve Repair and Regeneration ..................................................................................................................................................................15

Composite Tissue Injury Repair ...................................................................................................................................................................17

Transplantation ............................................................................................................................................................................................17

Epimorphic Regeneration (and associated methods) ..................................................................................................................................18

Progress Reports

Bone Repair and Regeneration

Project 4.2.1, RCCC–Advanced 3D Scaffolds for Large Segmental Bone Defects ................................................................................20

Project 4.2.2, RCCC–Optimizing Cell Sources for the Repair of Bone Defects ......................................................................................25

Project 4.2.3, RCCC–Advancing Bone Repair Using MSD .....................................................................................................................28

Project 4.4.9, USAISR–Bone Regeneration in a Contaminated Defect ..................................................................................................32

Soft Tissue Repair and Regeneration (Excluding Nerve)
Project 4.4.6, WFPC–Oxygen-Generating Biomaterials for Large Tissue Salvage ................................................................................36

Project 4.5.8, WFPC–Isolation and Expansion of Native Vascular Networks for Organ Level Tissue Engineering ................................40

Project 4.3.2, RCCC–Development of Bioabsorbable Tissue-Lined Stent for Vessel Trauma ................................................................42

Project 4.4.3a, RCCC–Functional Scaffold for Musculoskeletal Repair and Delivery of Therapeutic Agents .........................................45

Project 4.4.3b, RCCC–Functional Scaffolds for Soft Tissue Repair and Joint Preservation ...................................................................48

Nerve Repair and Regeneration
Project 4.4.4, WFPC–Peripheral Nerve Repair for Limb and Digit Salvage ............................................................................................51

Project 4.4.5, WFPC–Modular, Switchable, Synthetic, Extracellular Matrices for Regenerative Medicine .............................................54

Project 4.4.1/4.4.2, RCCC–Repair Segmental Nerve Defects ................................................................................................................57

Project 4.4.2a, RCCC–Cell and Bioactive Molecule Delivery to Enhance the Repair of Segmental Nerve Defects ...............................62

Composite Tissue Injury Repair
Project 4.4.3, WFPC–Engineered Delivery of Spatial and Temporal Cues for Composite Tissue Injury Repair .....................................67

Transplantation
Project 4.4.2, WFPC–Hand Transplantation for Reconstruction of Disabling Upper Limb Battlefield Trauma –

Translational and Clinical Trials ...............................................................................................................................................................71

Epimorphic Regeneration (and associated methods)
Project 4.4.1, WFPC–Blastemal Approach to Digit Reconstruction ........................................................................................................74

Project 4.4.7, WFPC–High-Throughput Approaches Applied to Tissue Regeneration ............................................................................77

Project 4.4.8, WFPC–Magnetophoretic Cell Sorting for Transplant Therapies .......................................................................................80

AFIRM Annual Report 2010 iii
III: Craniofacial Reconstruction
Background ......................................................................................................................................................................................................85

Unmet Needs ...................................................................................................................................................................................................86

Areas of Emphasis ...........................................................................................................................................................................................86

Bone Regeneration ......................................................................................................................................................................................87

Soft Tissue Regeneration ............................................................................................................................................................................89

Cartilage Regeneration (Focus: Ear) ...........................................................................................................................................................90

Virtual Modeling for CFR .............................................................................................................................................................................91

Progress Reports

Bone Regeneration

Project 4.1.2, WFPC–Space Maintenance, Wound Optimization, Osseous Regeneration, and

Reconstruction for Craniomaxillofacial Defects .......................................................................................................................................92

Project 4.1.3, WFPC–Novel Synthetic Bone for Craniofacial Application ...............................................................................................96

Project 4.5.1a, RCCC–Regeneration of Bone in the Cranio-Mandibulo-Maxillofacial Complex Using

Allograft Bone/Polymer Composites .......................................................................................................................................................99

Project 4.5.1b, RCCC–Regeneration of Bone in the Cranio-Mandibulo-Maxillofacial Complex ...........................................................102

Project 4.1.7, USAISR–Improving Cell Engraftment for Bone Repair ...................................................................................................106

Soft Tissue Regeneration
Projects 4.1.4 and 4.1.5, WFPC–Soft Tissue Regeneration .................................................................................................................108

Project 4.1.6, WFPC–Bioreactors and Biomaterials for Tissue Engineering of Skeletal Muscle .......................................................... 111

Project 4.1.2, RCCC–Develop Innervated, Vascularized Skeletal Muscle ............................................................................................115

Project 4.3.1, RCCC–Composite Tissue Allograft Transplantation Without Lifelong Immunosuppression ...........................................119

Cartilage Regeneration (Focus: Ear)
Project 4.1.1, WFPC–Engineered Cartilage Covered Ear Implants for Auricular Reconstruction .........................................................123

Project 4.5.4a, RCCC–Regeneration of Ear .........................................................................................................................................126

Project 4.5.4b, RCCC–Regeneration of Ear – Optimization of Scaffold................................................................................................131

Virtual Modeling for Craniofacial Reconstruction
Project 4.5.5, RCCC–Visualization of Patient-Specific Wounds and Injuries ........................................................................................135

IV: Scarless Wound Healing
Background ....................................................................................................................................................................................................139

Unmet Needs .................................................................................................................................................................................................140

Areas of Emphasis .........................................................................................................................................................................................140

Control of Wound Environment and Mechanics ........................................................................................................................................140

Therapeutic Delivery to Wounds ...............................................................................................................................................................141

Attenuation of Wound Inflammatory Response .........................................................................................................................................142

Scar Mitigation ...........................................................................................................................................................................................143

Recently Added Clinical Trial .........................................................................................................................................................................144

Autologous Fat Transfer for Scar Prevention and Remediation (AFT-SPAR) – Clinical Trial ....................................................................144

Progress Reports

Control of Wound Environment and Mechanics

Project 4.5.1, WFPC–A Device to Actively Control the Mechanobiology During Wound Healing and Prevent Scar Formation ...........145

Project 4.5.9, WFPC–Neodyne’s Device to Actively Control the Mechanobiology During Wound

Healing and Prevent Scar Formation – Clinical Trial .............................................................................................................................149

Therapeutic Delivery to Wounds
Project 4.6.3, RCCC–Therapy to Limit Injury (TLI) and Promote Non-Scar Healing After Burns and Severe Battle Trauma ...............152

Project 4.7.1, RCCC–Adipose-Derived Therapies for Wound Healing, Tissue Repair, and Scar Management ...................................155

iv AFIRM Annual Report 2010
our science for their healing
Project 4.5.2, WFPC–Regenerative Bandage for Battlefield Wounds...................................................................................................159

Project 4.5.5, WFPC–Scarless Wound Healing Through Nanoparticle-Mediated Molecular Therapies ...............................................163

Attenuation of Wound Inflammatory Response
Project 4.5.3, WFPC–Multifunctional Bioscaffolds for Promoting Scarless Wound Healing .................................................................166

Project 4.5.4, WFPC–Regulation of Inflammation, Fibroblast Recruitment, and Activity for Regeneration ..........................................169

Scar Mitigation
Project 4.5.6, WFPC–Delivery of Therapeutic Compounds into Injured Tissue ....................................................................................172

Project 4.5.7, WFPC–Scar Mitigation via Matrix Metalloproteinase-1 Therapy.....................................................................................175

V: Burn Repair
Background ....................................................................................................................................................................................................177

Unmet Needs .................................................................................................................................................................................................178

Areas of Emphasis .........................................................................................................................................................................................179

Intravenous Treatment of Burn Injury ........................................................................................................................................................180

Topical Treatment of Burn Injury ................................................................................................................................................................180

Wound Healing and Scar Prevention ........................................................................................................................................................182

Skin Products/Substitutes ..........................................................................................................................................................................183

Recently Added Clinical Trials ........................................................................................................................................................................185

WFPC ........................................................................................................................................................................................................185

RCCC ........................................................................................................................................................................................................185

Progress Reports

Intravenous Treatment of Burn Injury

Project 4.6.1, RCCC–Therapy to Limit Injury Progression, Attenuate Inflammation, Prevent Infection,

and Promote Non-Scar Healing After Burns and Battle Trauma ...........................................................................................................186

Project 4.6.2, RCCC–Mesenchymal Stem Cells for Burn and Wound Healing .....................................................................................190

Topical Treatment of Burn Injury
Project 4.2.3, WFPC–Novel Biomaterials That Support the Survival of Damaged Cells and Tissues ..................................................193

Project 4.6.4, RCCC–Polymeric Iodophor Absorbent Antimicrobial Wound Dressing...........................................................................196

Project 4.6.5, RCCC–Topical P12 Delivery via Biodegradable Fibro-Porous Mats for Burn Treatment ................................................199

Project 4.6.6, RCCC–Topical Curcumin-Containing Therapies to Promote Scarless Healing ..............................................................203

Wound Healing and Scar Prevention
Project 4.2.2, WFPC–Delivery of Stem Cells to a Burn Wound via a Clinically Tested Spray Device—

Exploring Human Fetal Skin Progenitor Cells for Regenerative Medicine Cell-Based Therapy Using Cell Spray Deposition ..............207

Project 4.2.4, WFPC–Artificial Extracellular Matrix Proteins for Regenerative Medicine ......................................................................211

Project 4.2.5, WFPC–In Situ Bioprinting of Skin for Battlefield Burn Injuries ........................................................................................214

Project 4.2.7, WFPC–A Multicenter Comparative Study of the ReCell® Device and Autologous

Split-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries .........................................................................................217

Project 4.6.7, USAISR–The Impact of Trauma on the Potency of Adult Stem Cells .............................................................................220

Skin Products/Substitutes
Project 4.2.1, WFPC–Tissue-Engineered Skin Products – ICX-SKN....................................................................................................223

Project 4.2.1a, WFPC–Tissue-Engineered Skin Substitute for Burns ...................................................................................................227

Project 4.2.6, WFPC–Amniotic Fluid Stem Cells for Burn .....................................................................................................................230

Project 4.2.8, WFPC–In Vitro Expanded Living Skin for Reparative Procedures..................................................................................234

Project 4.7.2, RCCC–Engineered Skin Substitutes ..............................................................................................................................237

Project 4.6.8, USAISR–Adipose-Derived Stem Cells for Tissue-Engineered Dermal Equivalent .........................................................241

AFIRM Annual Report 2010 v
VI: Compartment Syndrome

Background ....................................................................................................................................................................................................245

Unmet Needs .................................................................................................................................................................................................246

Areas of Emphasis .........................................................................................................................................................................................246

Cellular Therapy of Compartment Syndrome ............................................................................................................................................246

Biological Scaffold-Based Treatment of Compartment Syndrome ............................................................................................................248

Progress Reports

Cellular Therapy of CS

Project 4.3.1, WFPC–Cellular Therapy for Treatment and Consequences of Compartment Syndrome...............................................249

Project 4.3.2, WFPC–Use of Bone Marrow-Derived Cells for Compartment Syndrome .......................................................................253

Project 4.3.6, USAISR–Regenerative Medicine Approaches to the Treatment of Ischemia/Reperfusion Injury in Skeletal Muscle .....257

Biological Scaffold-Based Treatment of CS
Project 4.3.3, WFPC–Biodegradable Elastomeric Scaffolds Microintegrated with Muscle-Derived Stem Cells for

Fascial Reconstruction Following Fasciotomy ......................................................................................................................................260

Project 4.3.4, WFPC–Use of Autologous Inductive Biologic Scaffold Materials for Treatment of Compartment Syndrome .................264

Project 4.3.5, WFPC–Material-Induced Host Cell Recruitment for Muscle Regeneration ....................................................................268

VII: AFIRM Program Statistics

Introduction ....................................................................................................................................................................................................271

Personnel .......................................................................................................................................................................................................272

Honors and Achievements .............................................................................................................................................................................274

Publications and Presentations ......................................................................................................................................................................275

Inventions, Patent Applications, and Patents .................................................................................................................................................276

Developmental Accomplishments and Milestones .........................................................................................................................................277

Appendix A: Honors and Awards to AFIRM Faculty .............................................................................................................................................A-1

Appendix B: Publications and Presentations ........................................................................................................................................................B-1

Appendix C: Patent Applications and Invention Disclosures ................................................................................................................................C-1

Appendix D: Index of Team Leaders and Project Team Members........................................................................................................................D-1

vi AFIRM Annual Report 2010
Executive
Summary
The use of improvised explosive devices in Iraq treatments are needed to revolution-
and Afghanistan has caused a marked increase in ize the clinical rehabilitation of severely
severe blast trauma. Due to advances in body armor, injured service members.
quicker evacuation from the battlefield, and ad-
The Department of Defense established the Armed
vanced medical care, many of the injured survive to
Forces Institute of Regenerative Medicine (AFIRM)
face the challenge of overcoming severe limb, head,
in 2008 with the mission of developing new prod-
face, and burn injuries that can take years to treat
ucts and therapies to treat severe injuries suffered
and usually result in significant lifelong impairment.
by U.S. service members. This multi-institutional,
The burgeoning field of regenerative medicine interdisciplinary network of scientists has been
provides hope for restoring the structure and func- designed to accelerate the delivery of regenerative
tion of damaged tissues and organs and curing medicine therapies for severely injured U.S. service
previously untreatable injuries and diseases. The members. Centered around well-established, proven
concept of regenerative medicine—in its simplest research investigators, the AFIRM has been able
form—is to replace or regenerate human cells, to expand the rehabilitative medicine knowledge
tissues, or organs to restore or establish normal base, develop models of injury, and test advanced
function. Advanced technologies such as tissue re- technology products.
generation, bone scaffolding, and stem cell-enabled
AFIRM Annual Report 2010 vii
our science for their healing