Armed Forces Institute for Regenerative Medicine Pittsburgh projects
McGowan Institute for Regenerative Medicine investigators, unless otherwise noted
The Armed Forces Institute for Regenerative Medicine (AFIRM) is a multidisciplinary, multi-center partnership that will address needs related to the care of injured military personnel using innovative and advanced regenerative medicine-based therapies. This synopsis highlights the focus of the Pittsburgh team’s investigators.
Compartment syndrome
Increasing numbers of surviving armed forces personnel have blast, burn and penetrating injuries, most frequently to the extremities. A common blast-related injury is known as compartment syndrome, caused by severe swelling and increased pressure within tissue compartments. This can quickly lead to permanent muscle, nerve and vascular cell death, dramatically amplifying even simple injuries to the point of permanent disability despite prompt surgical attention. Pittsburgh’s AFIRM team will study a treatment approach involving a combination of stem and progenitor cells and inductive scaffold materials for the on-site reconstruction of functional compartment tissues. Projects include:
- Cellular therapy: Johnny Huard, Ph.D.
- Use of bone marrow-derived stem cells: Kenton Gregory, Ph.D.
- Biodegradable elastic polymer scaffolds micro-integrated with muscle-derived stem cells: William R. Wagner, Ph.D.
- Use of patient-specific inductive biologic scaffold materials: Stephen Badylak, D.V.M., Ph.D., M.D.
Limb and digit regeneration
The battle mortality rate for U.S. forces has dropped significantly since World War II. But these advances in medical treatment have come at a cost – an increase in the number of seriously injured soldiers who survive but are left with extraordinary, disabling injuries.
The restoration of functional limb and digit tissue involves the orchestrated growth and differentiation of multiple tissue types in a correctly oriented and appropriate pattern. The approaches that will be explored and developed in the AFIRM program include the creation of an amphibian-like limb-regeneration response structure called a blastema, the first step toward limb regrowth. In addition, investigators will study transplantation of entire hands using immune system-modification and development and refinement of innovative technologies to engineer complex digit and limb tissues. Tissue engineering projects will involve the control of blood vessel and nerve growth in composite tissue grafts, development of peripheral nerve conduit and synthetic materials, identification and sorting of key cell populations, and development of oxygen-generating biomaterials for tissue survival. Among Pittsburgh programs are:
- Blastemal approach to digit reconstruction: Dr. Badylak.
- Hand transplantation for reconstruction of disabling upper limb battlefield trauma
- Peripheral nerve repair: Kacey Marra, Ph.D., in collaboration with David Kaplan, Ph.D., Tufts University
Craniofacial reconstruction
The craniofacial complex, which includes the face and skull, is the window to the soul. Devastating facial injuries present an array of complex therapeutic challenges. Current techniques fall short of restoring anatomy and function. Regenerative medicine techniques aimed at restoration of craniofacial structures must address function as well as the aesthetic consequences of scarring and deformity. Advanced technologies for bone regeneration will include the use of nano-scale inorganic bioactive cements and naturally derived polymer hybrid materials that possess excellent bio-reactivity, biocompatibility, safety and regenerative capability. This combination material should result in structural and functional bone, free of infection. Pittsburgh area projects include:
- Novel synthetic bone for craniofacial regeneration: Charles Sfeir, D.D.S. Ph.D.
- Implantable engineered soft tissue for trauma reconstruction: J. Peter Rubin, M.D., Ph.D.
Inflammation control and wound healing without scars
Scar formation following injury is a major problem for U.S. soldiers and civilians alike, leading to disabilities in form and function. The annual economic burden of this problem in the United States has been conservatively estimated at more than $4 billion. Burn injuries are particularly prone to extensive and crippling scars. Particularly in the extremities, scars from burn injuries can restrict movement and limit function. Once a tendon or muscle is encased in scar, generally only surgical intervention will offer hope of improvement. Corrective surgery itself, however, can set off a new wound-healing response with associated risks for scarring. Pittsburgh area projects include:
- Multi-functional bioscaffolds for promoting scarless wound healing: Newell Washburn, Ph.D., Carnegie Mellon University and the McGowan Institute for Regenerative Medicine
- Regulation of inflammation, connective tissue cell recruitment and activity for regenerative healing: Patricia A. Hebda, Ph.D.
- Scarless wound healing through nanoparticle-mediated molecular therapies: Sandeep Kathju, M.D., Ph.D., Allegheny Singer Research Institute, Pittsburgh
- Scar mitigation via matrix metalloproteinase-1 tertiary therapy: Alan J. Russell, Ph.D.
Burn repair
AFIRM will include a comprehensive burn research program that will implement a number of regenerative technologies extending from the laboratory bench to clinical implementation to address burn repair. The increased survival of patients suffering from devastating burn injuries presents new challenges. Projects will seek to mimic the scarless healing seen in the womb in adult wounds by providing regenerative extracellular matrix components, by using anti-inflammatory agents and by controlling the selection and recruitment of connective tissue cells into the wound.