In medicine, necessity certainly does springboard invention. For the U.S. Armed Forces, regenerative medicine is probably a necessity no one wished they’d have to tackle. But the need is of course there. We’ve all seen the images of U.S. soldiers returning home with battle scars that have no hope of healing. Lost limbs and improvised explosion device injuries (accounting for a startling 75% of injuries according to the Journal of Orthopaedic Trauma) are now common place in military hospitals. Today we’re able to keep wounded soldiers on the battlefield alive, but they are returned home severely disabled. Two years ago the government decided to do more than just search for better artificial limbs or technologically-advanced prosthetics. Instead the Armed Forces made the bold step to dive head first into the futuristic world of regenerative medicine.
And so the Armed Forces Institute of Regenerative Medicine (AFIRM) was born.
AFIRM Press Conference / Wikimedia CommonsIt almost makes for the perfect sci-fi movie: combine top secret military maneuverings with experimental medicine and visions of lab-grown limbs get conjured up. Except there is very little secrecy or military status quo to this project. This project is ambitious not just because it’s about stem cells and growing new body parts. It’s also unique in its scope and collaborative spirit. This is after all the first time in the country’s history where every branch of the military has come together and aligned themselves with top-tier medical researchers.
A Web of Research
The Department of Defense describes AFIRM as a “multi-institutional, interdisciplinary network working to develop advanced treatment options for severely wounded servicemen and women.” Receiving funds from the U.S. Army Medical Research and Materiel Command along with other branches of the service including the VA and matched funding from public and private donors, the Institute is divided into two distinct consortia, with each working in conjunction with the U.S. Army Institute for Surgical Research (USAISR) out of Fort Sam Houston, Texas.
The Rutgers and the Cleveland Clinic consortium:
- Rutgers, The State University of New Jersey
- Cleveland Clinic
- Carnegie Mellon University
- Case Western Reserve University
- Dartmouth Hitchcock Medical Center
- Massachusetts General Hospital/Harvard Medical School
- Massachusetts Institute of Technology
- Mayo Clinic
- Northwestern University
- Stony Brook University
- University of Cincinnati
- University of Medicine and Dentistry of New Jersey
- University of Pennsylvania
- University of Virginia
- Vanderbilt University
The Wake Forest University and The McGowan Institute for Regenerative Medicine at the University of Pittsburgh consortium:
- Wake Forest University
- McGowan Institute for Regenerative Medicine, University of Pittsburgh
- Allegheny Singer Research Institute
- California Institute of Technology
- Carnegie Mellon University
- Georgia Institute of Technology
- Oregon Medical Laser Center
- Rice University
- Stanford University
- Tufts University
- University of California, Santa Barbara
- University of Wisconsin
- Vanderbilt University
Each consortium received $42.5 million to divvy up over five years (so three more years to go!) but additional public and private sources meant that nearly triple that amount could be counted on for spending, with the lead groups handling distribution.
But enough about budgets, let’s get to the research!
The main goal of this Institute is to streamline research and turn bold aspirations into actual outcomes. From the Institute’s web site: “AFIRM was designed to speed the delivery of regenerative medicine therapies to treat the most critically injured service members from around the world, but in particular those coming from theaters of operation in Iraq and Afghanistan.”
AFIRM’s areas of focus are:
- Limb Repair
- Craniofacial Repair
- Burn Repair
- Scarless Wound Repair
- Compartment Syndrome Repair
To quicken the pace of research and to deliver regenerative medicine to patients faster than surgeons might otherwise expect, the Institute decided to stack the deck by relying on academic research teams that have already shown great promise in their respective regenerative projects.
An interesting offshoot of these academic and defense collaborations is the role the medical device market has played. Ever a willing participant in innovation, commercial partners are clamoring to join this exclusive club with the benefit of future civilian applications dancing in their heads.
Like medical innovations of the past, today’s battlefield injuries are spurring medical researchers on, challenging them with polytraumatic blast injuries that generally involve massive soft tissue loss, infection and damaged blood vessels. But there’s also no denying that any regenerative advancements for wounded warriors will have beneficial results for the rest of us too.
Edward Anthony Rankin, M.D., Chief of Orthopaedic Surgery at Providence Hospital in Washington, DC, and former Chief of Orthopaedics at Walson Army Hospital and President of the AAOS (American Academy of Orthopaedic Surgeons), says AFIRM is an impressive example of collaboration and funding. “AFIRM is really spectacular and the fact that defense sectors are working with civilian institutes is really promising. I don’t think we have seen any type of collaboration on the scale before.” Rankin also looks to the future applicability of this research. “Many major medical advances have come from war. If you look at how our trauma centers are set up, that comes directly from lessons we learned during the Vietnam War. This research in time will undoubtedly become beneficial to the civilian population. But it might not have become a reality if it had not been for this need.”
The Rutgers/Cleveland Clinic Consortium (RCCC)
Led by Rutgers’s Professor Joachim Kohn, Director of the New Jersey Center for Biomaterials and George Muschler, M.D., orthopedic surgeon at the Cleveland Clinic, RCCC has a host of exciting research projects going on. Here are just a few of the highlights:
The RCCC Limb Salvage and Regeneration Program
- Optimizing Cell Sources for Repair of Bone Defects: The Cleveland Clinic is working to develop tools that will allow for the harvesting, collecting, processing and concentrating of key osteogenic connective tissue progenitors (CTP-Os) for bone repair. This includes a machine that can be used in the OR that will deliver rapid concentration and selection of stem cells.
- Molecular Surface Design (MSD) for Controlled Cell- and Tissue-Scaffold Interactions: How do you get cells to play nice with implanted material? The goal here is to create a molecular surface design method that cells and tissues won’t be able to resist. The bioactive material could then be attached to bone scaffolds. The beauty of this project is that it can work hand-in-hand with other AFIRM projects that focus on developing advanced scaffolds.
Hand Transplant / Wake Forest Pittsburgh Consortium
In addition to these Limb Salvage projects, the RCCC is also working on nerve regeneration (Optimizing Nerve Conduit Scaffolds for the Repair of Segmental Nerve Defects, Optimizing Cell Sources and Local Drug Delivery to Enhance the Repair of Segmental Nerve Defects), facial reconstruction (maybe you heard about the nation’s first full facial transplant?) and burn/scaring projects.
The Wake Forest Pittsburgh Consortium
Similarly, the Wake Forest Pittsburgh Consortium is focused on individual projects within the five areas of AFIRM focus, led by Anthony Atala, M.D., of the Wake Forest Institute for Regenerative Medicine and Rocky S. Tuan, Ph.D., Director of the Center for Cellular and Molecular Engineering at the University of Pittsburgh. Here’s what they’ve got going on:
- Recruiting Cells for Regeneration: The inspiration for this project came from the humble salamander, which can re-grow limbs as needed. The team is hoping to figure out a mechanism for bringing a large number of stem cells to the site of an injury where re-growth is needed. But the team also has to figure out how to tell the cells what’s needed to be grown—a finger, a toe, an arm?
- Hand Transplantation: Although hand transplants are currently available, one major drawback to the procedure is the course of disruptive anti-rejection drugs that a patient is required to take for a lifetime. This research team is working to reduce this burden by using bone marrow cells with novel proteins to allow for better acceptance of the transplant.
- Oxygen Generating Biomaterials: When blood supply is road blocked because of injury, tissue is deprived of oxygen which limits healing. But if there was an injectable form of oxygen-producing biomaterial, this could not only nourish the tissue but help foster viable blood vessel networks.
- Identifying Genes Involved in Limb Regeneration: Taking a nod from the promise of extracellular matrix research, this project is working to identifying the genes that play a role in regeneration.
Ironically, regenerative medicine itself is getting renewed life from this project. After an initial surge in interest at the turn of the millennium, interest seemed to flounder when the realities of research showed that progress would not be an overnight sure-thing. AFIRM is proving that is takes a strong commitment and serious funding to allow scientists to explore these ambitious possibilities. But the collaborative spirit of divergent groups working together is also pretty darn inspiring in itself.
