In the past few years, increased funding and effort have gone into pushing the boundaries of the possible, of going beyond even the most advanced traditional prosthetics to technologies that have long been the staple of science fiction, not clinical reality. These include bone and tissue regeneration, hand and face transplants, biomechanical interfaces (which could provide brain control of prosthetic arms and hands, being able to “feel” objects, etc.), cloning replacement parts using the recipient’s own DNA to avoid rejection, and more.

It all began with a change in attitude and perspective among doctors, both those in the battlespace dealing with wounded warfighters in the “golden hour” after injury and those at advanced treatment and rehabilitation facilities in the United States and at Landstuhl Regional Medical Center in Germany, the first stop between combat and CONUS for most severely wounded warriors.

“Early in the war there were issues related to the salvaging of limbs. When we discovered better ways to do that, we got that information to the field to ensure all limbs that can be saved are saved,” Dr. Jonathan Woodson, the assistant secretary of Defense-Health Affairs, said. “So the system has done a good job of being a learning organization and improving strategies for care.”

Like Woodson (an Army Reserve brigadier general), Air Force Lt. Col. Michael R. Davis, chief of Reconstructive Surgery & Regenerative Medicine at the Army Institute of Surgical Research (ISR) – has served as a combat surgeon. His experiences in theater and at USAF hospitals in the United States led him to focus on finding faster and less painful ways to improve both functionality and aesthetics for warfighters with extremities loss or severe damage.

“As a surgeon stationed in Afghanistan, I witnessed firsthand the impact of that on our troops and, back here, I have seen an increasing capability in being able to care for these injured soldiers,” he said. “We have a great responsibility to develop techniques and technologies for those in need. And with the conflicts drawing to a close, there will be a heavy emphasis within the military medical community to further those advances.

“In the past, the standard was to reconstruct everyone, salvage every possible limb. But over time, as prosthetics have become more advanced and the benefit of a prosthesis has gone up, we have seen many cases where patients are more debilitated than they would have been with primary amputation. That has caused a paradigm shift in the orthopedic and reconstruction communities about how they feel about reconstruction versus primary amputation and prosthesis.”

The new prosthetics provide more than just better functionality, added Lt. Col. John M. Scherer, director of the Army’s Clinical and Rehabilitative Medicine Research Program (CRMRP), they offer the prospect of a return to duty or a far more “normal” civilian life.

“Most prosthetics before were not designed with a highly active 20-year-old amputee in mind. In addition, we now are looking at them from a combat environment requirement, because we have deployed people back into the combat zone with lower extremity prostheses,” he explained.

“Outside the military, they normally don’t have to be waterproof or sandproof because, if the weather is bad in the U.S. and you have a powered prosthetic limb, you either don’t go out or make sure it is protected from the weather. You can’t do that in combat, so there have been changes to make the batteries last longer and function in harsh environments – sand, heat, water, exposure – as well as giving them additional functions, such as the ability to go backwards.”

CRMRP is working with the Military Amputee Research Program to capitalize on advancements in neural interfaces, nanotechnology, and prosthetic design to improve foot and knee prosthetics, knee prosthetic control, and haptic [touch] feedback. Their coordinated research is designed to improve prosthetic performance through advanced clinical practices and strategies, but also will contribute to the overall advancement beyond prosthetics.

The vast majority of advances during the current conflict have involved replacing amputated feet and legs.

“Microprocessors in the knee have replaced control by the physics of the prosthetic movement. Basically, that makes you fall less and your gait is closer to normal, so you don’t injure the healthy limb. From that perspective, there has been a huge improvement in the ability to walk in a normal way compared to how you would have moved prior to these advancements,” Scherer said.

“There really has not been a lot of effort in changing the current state of the art for upper extremities – which includes the ‘hook’ that has been used for quite a while. There are lots of reasons for that, but DARPA’s [the Defense Advanced Research Projects Agency’s] prosthetics program has brought a lot of robotic improvements to upper extremity devices and we hope to go into clinical trials soon. Most of the biomechanical neural interfaces to prosthetic limbs also are being done by DARPA. And that is the holy grail – making the prosthetic work with a neural interface, with feedback, so you can actually feel in your ‘fingertips’ what you are touching and do direct movement.”

Advancements in lower limb prosthetics that have enabled many amputees to regain a more normal life also have resulted in a new development that concerns many in military medicine: Warfighters whose damaged feet or legs were saved by advances in battlefield and follow-up surgery asking to have the limb amputated anyway because they believe a prosthetic would give them greater functionality than their reduced capability real foot or leg. Those advances also give warfighters other “positive” arguments for amputation.

“Someone who undergoes primary amputation will heal and get through the process of rehab much faster. Someone who undergoes limb salvage could face 10 or more operations over a period of years before they see adequate healing and rehabilitation – if they ever get to a point of full functionality. So it requires very careful patient selection for complex reconstruction and who we recommend for primary amputation and fitting of an advanced prosthesis,” Davis said, but added new options are becoming available. “You can’t compare a prosthesis to a natural limb, but you can compare it to a reconstructed limb using techniques such as free tissue transfers and bone grafting.”

Historically, medical research has been an isolated pursuit, both in terms of competition in academia and industry and in a single-issue or application focus, such as brain injuries, orthopaedics, dentistry, etc. In recent years, however, the U.S. Military Health System has sought to bring multiple university and commercial researchers and disciplines together to pursue specific issues but also to share knowledge and find new applications for what works in one area to the needs of another.

Col. Robert G. Hale, commander of the Army Dental Corps’ Dental and Trauma Research Detachment (DTRD), spends the majority of his time on issues related to regenerating bone, tissue, muscle, and nerves, including face transplants, and ways to block or kill biofilm, which causes plaque and gum disease in the mouth but also keeps open wounds from healing. Tapping into DoD-sponsored multidiscipline research has brought new solutions to his concerns, while DTRD advances are finding applications in amputation and prosthetics – and moving beyond both.

“Advanced bone regeneration biomaterials, better than our most recent capabilities, could improve patient outcomes with fewer and less invasive surgeries, both for craniofacial and limb salvage. Another advance is adipose fat, which regenerates very quickly. If we can tap into the regenerative abilities we know exist in fat and place that into a wound, it can heal with less scarring and improve mobility anywhere on the body there is movement,” he said.

“A follow-on, perhaps starting next year, will be a stem cell-enriched fat. We may not be able to regenerate an arm muscle in the next 10 years, but maybe in 15 or 20 years we can slide a scaffold under the skin, then inject stem cells that will homein on that scaffold and help patients recover better.”

Tissue scaffolds are considered the medical implants of the future. Made of fully degradable biomaterials, they support cells at the site of injury and assist the body in growing new, functional tissue. Once that new tissue has successfully replaced damaged or lost tissue, the body’s natural systems will dissolve and recycle the scaffold.

Currently, the cells used in that process are either produced synthetically or taken from the patient’s body and processed for application to the wound or transplant area. That process is expected to become substantially more successful with the use of stem cells – unspecialized cells with the ability to transform into specialized cells in the body. Adult stem cells, recently found to be both more plentiful and more adaptable than previously thought, are at the center of many medical research programs.

While those efforts cannot regenerate entire limbs – yet – in combination with bioactive factors and biomaterials, stem cells can form new bone, nerves, and soft tissue (skin, tendons, muscles, blood vessels) to replace damaged tissues and speed recovery. Even if salamander-like limb regrowth does become possible, however, growing a new hand, arm, foot, or leg that would be a true part of the patient’s body may have more drawbacks than advantages.

“There are studies under way to figure out how other organisms can regenerate body tissues and hopefully translate that into a human ability to do the same. The answer probably will lie with stem cells, but to regenerate something as complex as a hand is still science fiction,” Davis said.

“In another hundred years, will we be further along in terms of that kind of capability? Yes. The problem is, when someone needs a functionalized limb, growing one can cause substantial delay. So even if that becomes possible in the future, the time involved to complete the process may be prohibitive.”

Continued advances in limb salvage that return the damaged hand or leg to an acceptable level of function and appearance are seen as the best hope to avoid future amputations. For those who already have lost a limb or future wounded warriors whose limbs cannot be saved, if full regeneration is not a viable option, the ultimate answer may lie in improved biomechanical interfaces and – for hands, at least – transplants, from human donors or using hands cloned from the patient’s DNA.

Because a cloned limb would take as long to grow into adult size and appearance as the original, that source for a hand transplant would be a long-term solution, requiring some other approach immediately after amputation. While using a donated hand for transplant appears to offer the best choice, as with any surgical procedure, it has drawbacks, including an average 16-hour operation – twice that of a heart transplant. Finding a match also is more difficult than with a heart – in addition to all the usual blood and tissue match requirements, it also has to match the recipient’s age, sex, hand size, and skin color.

“There is a debate over what would make a hand transplant standard care. For a bilateral hand amputee, there is no better way to rehabilitate someone than through a transplant. But what if it is a single hand – either dominant or non-dominant? Those questions are still subject to determination, and whether they are still experimental or part of standard care is still a great debate within the military and civilian medical communities,” Davis explained.

“There needs to be great collaboration among the facilities doing these procedures to answer those questions and advance the field. And we are seeing that, with centers coming together and forming groups to answer these questions. We really need to go forth responsibly, not just doing transplants because we can, but because we should. Ultimately, those are patient decisions, but we need to be in the best position to recommend a course of care.”

One of those facilities is the Atlanta VA Medical Center and its affiliate, Emory University, where Dr.  Linda Cendales performs hand transplants and is conducting a new VA study tracking transplant patients.

“In my experience, patients report the new hand has been better for them than the prostheses they were wearing,” she said. “It’s a human hand, not a device. The hand recovers sensation and patients are able to perform activities such as turning doorknobs, holding the newspaper, tying their shoes. It’s not a life-saving organ – it’s a quality-of-life transplant.

“We have a multidisciplinary team that is patient-centered. Our program aims to provide another option for a selected group of patients and to provide the best options overall for our amputees. If it’s a prosthesis, the best prosthesis; if it’s a hand, the best-matched human hand.”

The other leading option for the future is a greatly improved biomechanical interface – linking the amputee’s living tissue to a prosthesis. Some elements of that already are available, some are in or close to beginning clinical trials, some are still in the lab, and, for a few, science and technology have not yet advanced far enough to move them from science fiction to science fact.

One that recently did make that transition is 3-D bio-printing – similar to industrial fast prototyping, where a solid object is built, layer by layer, from special plastics or other materials. In this case, researchers at Wake Forest University have successfully “printed” human skin. While a revolutionary leap in current technology, it may be years from wide-scale clinical use for other body parts.

“Being able to print biological materials, such as skin, will greatly advance our ability to create functionalized synthetic reconstructive tissues. It holds a lot of promise, but bio tissues are complex and much more difficult to synthesize and print than industrial materials,” Davis noted. “So I think that capability will come, but not in the near term.”

In the meantime, tissue regeneration in vitro, using processed body cells or adult stem cells, may be combined with new titanium bone implants to resolve a number of problems with the interface of prosthetics and human bodies. First on that list is bacteria entering the space where the prosthetic connects to the body; second is the body’s tendency to reject the prosthetic as a “foreign body.”

Both are being addressed by VA-sponsored research led by Thomas Webster, associate professor of engineering and orthopaedics at Brown University. Webster’s team has developed two techniques, which may work together: first, modifying the surface of titanium leg implants to promote cell growth and create a natural skin layer to seal the gap; second, covering the implant connection point with a molecular chain of proteins to hasten skin growth.

“You definitely have a complete layer of skin,” Webster said of the process. “There’s no more gap for the bacteria to go through.”

Improving prosthetics and how they connect to and work with the body, and developing new techniques to replace prosthetics or even avoid the need for amputation are subjects of active and intense research across the DoD, VA, academia, and industry. While spurred by a modern record number of severe combat limb injuries and amputations, it is an effort that will continue long after the last U.S. warfighter leaves Afghanistan.

“The biggest point to all this is we have a responsibility to get the best possible outcome for our wounded service members, who risk their lives every day and many suffer devastating injuries. I’ve seen these injuries firsthand while stationed in Bagram [Air Base, Afghanistan] and, knowing our current capabilities, realized the long-term outcome was not nearly as good as we could achieve. And they deserve the best outcome possible,” Davis concluded.

“Many within the military have the capability to advance these techniques, which in combination with top-level support and funding for this research, creates an environment where we can help them. What this does is create hope for our warfighters, which is one of the most positive outcomes of what we do, that a wounded service member can regain functionality they lost to injury.”

This article first appeared in The Year in Veterans Affairs & Military Medicine: 2011-2012 Edition.