New Hope for Soldiers Disfigured in War

By Col. Robert Hale’s count, Todd Nelson had already cheated death twice when he arrived at Brooke Army Medical Center in San Antonio. A 34-year-old senior logistics supervisor based in Kabul in Afghanistan, Staff Sgt. Nelson had escaped injury on hundreds of convoys by relying on speed, agility and a little luck. On a hot August day in 2007, a month before he was due to go home, his luck ran out.

Nelson and his partner, Chris Sanders, were headed back to camp when a Toyota Corolla pulled in front of their truck. Sanders hit the brakes and swerved to the left, then locked eyes with the car’s driver, who flipped a switch, blowing his car, and himself, to bits. 

Sanders, shielded by Nelson, escaped with minor burns. Nelson took most of the blast in the face. The explosive force crushed his facial skeleton and fractured his right leg. Shrapnel and glass tore through his legs, sinus cavity and right eye, and twisted like a corkscrew through his right cheek. A fireball hotter than molten rock seared his right side from the bottom of his foot to the top of his crown, burning his face nearly through to the bone.

Field medics doubted Nelson could survive evacuation to the U.S. military hospital in Germany, much less to Brooke’s burn facility in Texas. When he arrived at Brooke two days later, hospital staff made plans to donate his organs. 

That turned out to be premature. But when Hale, one of the Army’s top facial trauma surgeons, first saw Nelson, still clinging to life, he also saw the young man’s future. Hale knew that even if his patient survived, no doctor could fully restore what was lost in Afghanistan: the face that Nelson and his friends and loved ones knew as Todd. And the ability to pass strangers on the street without attracting stares.

Hale had left a thriving Los Angeles plastic surgery practice in 2003 to serve America’s wounded. But while working in dusty Army field hospitals during tours in Kuwait and Afghanistan, he found himself cursing the pitifully inadequate tools available to counter the human wreckage left by suicide bombs. Even at Brooke’s state-of-the-art facilities, he had to treat the facial wounds of a new kind of warfare with techniques that had changed little since their invention almost a century ago. Modern medicine had no answer for homemade bombs that pulverize bone and liquefy flesh. Hale, moved by Nelson’s plight, vowed to bring the tools of medicine in line with the weapons of war. 

The history of wartime medicine has long been written by battle-tested surgeons like Hale, who, in a strange symbiosis between war and medicine, have conjured new remedies to heal the wounded. The trenches of World War I exposed men’s faces to a fusillade of shrapnel, spurring unprecedented surgeries to reconstruct what remained. The mine-filled battlegrounds of Korea and Vietnam likewise gave birth to techniques for repairing severed arteries and veins to salvage limbs.

Most recently, the improvised explosive devices, or IEDs, that littered the streets and battlefields of Iraq and Afghanistan led to innovations in combat medicine and evacuation procedures. These advances, combined with enhanced protective gear, helped produce the highest U.S. combat survival rates in history: Today less than 10 percent of combat casualties die from their wounds, compared with 19 percent in World War II and 16 percent in Vietnam. 

But body armor and helmets don’t protect the face. And the advances that saved so many lives in Iraq and Afghanistan left surgeons struggling to fix harrowing facial injuries in numbers unrivaled since World War I. Some 40 percent of those severely wounded in Iraq and Afghanistan suffered devastating blows to the face. All Hale and his fellow surgeons could offer was the prospect of 30, 40, even 100 operations that closed wounds but left cheeks without feeling, mouths too small to open, eyelids locked in position. Countless veterans, Hale knew, would live out their days with faces they would not recognize as their own. 

A fit 57-year-old with a strong jaw and imposing presence, Hale is leading a massive effort to bring the science of facial repair into the 21st century. Now commander of the Dental and Trauma Research Detachment at the U.S. Army Institute of Surgical Research in San Antonio, he has brought the best and brightest minds of regenerative and transplant medicine to the task of healing some of the most grievous wounds of modern warfare. 

Hale was seeing patients at his Los Angeles surgery center shortly after Sept. 11, 2001, when a U.S. Army clerk called, asking if he would return to active duty. The surgeon had been honorably discharged five years before, after deep cuts in military spending. But Hale had always enjoyed the yearly check-ins with his Reserve unit. And to his dismay, he increasingly found himself “taking care of rich people with small problems.” When the Army called, Hale said yes.

By September 2003 he was in a field hospital in Kuwait, just south of U.S. military actions in Iraq. President George Bush had announced the end of major combat operations in Iraq several months before, and Hale expected the occasional casualty amid routine dental care. And that’s what he saw — at first.

Today less than 10% of combat casualties dies from their wounds, compared with 19% in World War II and 16% in Vietnam. But body armor and helmets don't protect the face.

But within weeks, guerrilla warfare kicked into high gear. Hale saw casualties every day, most with jaws severed by high-powered rifles or faces crushed in vehicle rollovers. Frequently, all he could do was jam pins through remnants of skin to temporarily hold bone fragments together, prepare his patient for evacuation and hope for the best. He quickly exhausted the field hospital’s surgical supplies and called his old sales rep, who express-mailed a donation of $300,000 worth of bone plates and screws. 

Hale’s tour was supposed to last three months, but when his commander said they didn’t have a replacement for him, Hale asked his wife to sell his surgical practice and agreed to stay on another 90 days. 

After six months in Kuwait, Hale was sent to an active combat base in Afghanistan. There he saw as many as 15 patients a day bearing what he calls the “wicked injuries” of IEDs. 

The Army finally found a replacement for Hale in August 2004. Exhausted from 11 months’ service, he boarded a military jet to Germany and slept the whole way. Home in Los Angeles, Hale opened his mailbox one day to find two Bronze Stars for his extended service, one for each theater of war. Slowly, he recovered from the strain of combat care and saw a few old patients at a friend’s office.

But Hale’s appetite for private practice was gone. In March 2005, he dusted off his uniform, rejoined the Army full time and moved with his wife and two young sons to San Antonio to help soldiers like those he’d seen overseas. He joined the teaching faculty at Brooke, preparing doctors and nurses headed to combat zones for the horrific facial injuries they’d see — and the frustration they’d feel when they couldn’t repair the damage. 

Hale’s own frustration grew as he treated the wounded at Brooke with tools from his grandfather’s war — creating lips from tongues, fashioning jaws from leg bones, papering faces with skin taken from wherever he could get it. Inevitably, he’d reach a point where he was just “dragging scar tissue around,” he says. 

Then, in November 2005, French surgeons performed the world’s first partial face transplant, on a woman whose Labrador mix had mauled her. Hale immediately saw the technology as a wounded soldier’s ticket to a new life. He flew to Washington, D.C., hoping to persuade military leaders to fund transplant research. 

But the brass weren’t buying it. Face transplants require a lifetime of immune-suppressing drugs to keep the body from rejecting the tissue. The drugs increase patients’ susceptibility to infections, cancer and other serious health problems, and Hale’s superiors believed the risk and expense were unjustified for injuries some considered cosmetic. 

Hale returned to Brooke, resolved to make do with the tools he had. 

Then he met Todd Nelson.

When Nelson arrived in San Antonio in 2007, doctors scrambled to save his life. Hale, by then Brooke’s director of oral and maxillofacial surgery, evaluated the wounded soldier’s face three days later. 

The IED blast had driven dirty shards of metal through Nelson’s right eye and sinus cavity, crushed his facial bones and melted the skin on his face. It was a pattern of injuries unknown in the civilian world, Hale says: “You’d be seeing that kind of patient if he was hit by a train, then lit on fire and shot.”

Nelson spent the next six weeks in a drug-induced haze as Hale and the Brooke trauma team started to rebuild his face. Their priority was to protect Nelson’s charred flesh from an infection that could turn deadly. The flames that destroyed Nelson’s skin allowed microbes to invade the wound and amass into slimy sheets of bacteria, called biofilms. Biofilms can form within hours of injury and cause lingering, difficult-to-treat infections that, even when they don’t kill, provoke inflammation — a major impediment to scarless healing.

Surgeons prevent biofilms in limbs by removing all the wounded tissue, amputating if necessary. But they can’t amputate a face. Conventional antibiotic and disinfectant treatments don’t work well on face burns, so Hale’s team simply washed Nelson’s wounds to control infection and waited for the blistered skin to fall off. 

When the singed flesh on Nelson’s right ear and nose disintegrated after two weeks, the team started to reconstruct his skin. They gingerly removed remnants of dead skin and scraped off a biofilm growing underneath. Then they temporarily covered Nelson’s face with cadaver skin to keep bacteria out and prepare the wound for permanent grafts.

After two weeks, Nelson’s body unleashed a massive inflammatory response that rejected the alien skin. The inflammation set the stage for bad scarring, but the cadaver skin also triggered the blood vessel growth needed to support grafts with skin taken from his chest and arms. 

Facial trauma forces doctors to abandon a fundamental principle of plastic surgery: Replace like with like. Only the face has skin supple enough to smile and frown. When facial skin is destroyed, nothing can adequately replace it. The grafts that best approximate the look and feel of a face are “full-thickness” grafts, which involve harvesting the outer (epidermal) layer of skin along with the underlying (dermal) layers from elsewhere on the body. But such grafts are often difficult to harvest, leave deep wounds behind and fail when blood vessels can’t snake through the thick tissue. Hale reserved full-thickness grafts for Nelson’s lips and eyelids and used “split-thickness” grafts, which harvest only the epidermis and a fraction of dermis, to rebuild the soldier’s cheeks, forehead and crown. 

Nelson emerged from his six-week fog after 20-odd operations. He’d lost his right eye, had no right ear or much of a nose, and couldn’t open his mouth wide enough to eat a hamburger. Thick, painful scars tugged at his upper lip, leveled his nose and retracted his eyelids. Hale would have to untangle the knotted scars with operations that could take years. Hale asked Nelson if he had a priority. Nelson did: More than anything, he wanted to eat and breathe normally, and to have a face that didn’t shock people. 

That meant regrafting Nelson’s cheeks, nose and eyelids, but after all the surgeries, Nelson had very little healthy skin left to harvest. To get skin for Nelson’s cheeks, Hale used a variation on a technique invented in 1917 by Sir Harold Gillies, widely hailed as the father of plastic surgery. Hale cut a slit in Nelson’s shoulders and inserted a deflated tissue expander under the skin, adding saline twice a week for three months until Nelson resembled a defensive lineman. He then carved flaps of skin from each of Nelson’s shoulders, flipping the free ends up to Nelson’s cheeks. These so-called supraclavicular flaps use the blood supply from the supraclavicular artery at the base of the neck to nourish the graft. But the procedure required Nelson’s shoulders to stay stitched to his cheeks for a month. 

Hale knew what a nightmare it was for Nelson to endure so many debilitating surgeries, but he encouraged him to hold out a little longer so the surgical team could at least deliver the nose and eyelids they’d promised.

Meanwhile, Hale searched for ways to generate new tissue without treating patients’ bodies as spare parts factories. Scouring research journals for devices to regenerate skin and bone, he found tantalizing possibilities, but none that could treat catastrophic facial injuries like Nelson’s. Hale would need to come up with his own research plan. 

Throughout Nelson’s treatment, Hale urged Army leaders to fund discoveries to help gravely injured veterans. Whether moved by those pleas or by the steady stream of gruesome casualties, the Army in 2008 launched an unprecedented collaboration between military researchers and academic and industry scientists called the Armed Forces Institute of Regenerative Medicine (AFIRM). With $265 million and a research mandate to help severely wounded veterans return to normal life, AFIRM focused on five goals: salvaging limbs, preventing surgical complications, enabling scarless healing, restoring skin after burns and rebuilding faces. Hale was tapped to help researchers identify the most promising technologies to repair broken faces. 

He soon realized none of his AFIRM collaborators had seen anything like the devastation caused by IEDs. He persuaded Nelson, still undergoing treatment but living at home in San Antonio, to join AFIRM’s science advisory committee and help researchers understand the magnitude of the challenge. 

At one committee meeting, Hale explained his biggest frustration with available technologies to heal severe burns: None was designed with the face in mind. Nelson’s case illustrated the problem. To treat the wounds on his limbs and side, doctors used a pliable, two-layer skin substitute called Integra. The base layer, a porous matrix of collagen and other molecules derived from cow and shark tissue, mimics skin’s structural components to keep the wound from contracting as new dermal cells and blood vessels grow through the matrix. A top silicone layer acts like epidermis to keep out bacteria.

Facial trauma forces doctors to abandon a fundamental principle of plastic surgery: Replace like with like. Only the face has skin supple enough to smile and frown.

Working on Nelson’s bodily wounds, his surgeons covered each piece of Integra with an antibiotic-soaked sponge and ran a tube from the sponge to a vacuum pump. These vacuum-assisted closures, or wound VACs, sucked out fluids to reduce swelling and inflammation, a critical step in scarless healing. Nelson’s body absorbed the synthetic collagen within a few weeks, as his regenerating dermal cells released their own. His doctors then replaced the Integra’s silicone “epidermis” with split-thickness grafts taken from Nelson’s back.

But Integra and wound VACs were both designed for flat surfaces on the body. When Hale cut out small pieces of Integra for grafts on the face, they blistered against the irregular curves. Likewise, wound VACs needed an even surface to apply suction. Trauma specialists had always assumed both Integra and wound VACs were unsuitable for treating massive facial wounds.

Tending to Nelson led Hale to question those assumptions. Maybe there was a way to embed several dozen mini wound VACs throughout a face mask to achieve the same, or even better, results. The custom-fit “biomask” Hale envisioned would pump out the fluids that impair healing and lead to scarring. It would also deliver antibiotics to control infection and signal molecules known as growth factors to accelerate skin regeneration.

He shared his vision with his AFIRM collaborators: First, he’d scrape away all a patient’s scars to prepare a clean, smooth wound bed. He’d cover the wound with the biomask to prevent biofilms from growing, minimizing scarring. Then he’d place a skin substitute over the wound — an Integra-like product suitable for the face — and use the biomask again to hasten healing and protect the regenerating skin. Finally, he would suck out stem-cell-rich fat from the patient’s belly and inject it into a layer under the dermis to replenish the fat that keeps skin elastic and soft.

Nelson, listening to Hale explain his idea, realized his doctor imagined waiting until a patient had emerged from sedation and could consent to trying the biomask. By that point, the patient would have undergone multiple operations. “Why wait?” he asked Hale. “Just fix me the right way the first time.”

Hale rethought his strategy. To stop scarring in the first place, as Nelson was suggesting, he’d have to close wounds faster, without trapping bacteria under the skin. But how?

Before the year was out, he got his answer. In 2009, the Army named Hale commander of its Dental and Trauma Research Detachment, which was changing its focus from dentistry to facial trauma. Hale couldn’t have asked for a better fit. DTRD’s science director, Kai Leung, had discovered a molecule in saliva that was particularly effective at killing the bacteria that cause dental plaque — the biofilm scourge of dentistry. 

Hale realized that a synthetic version of the molecule that Leung had used for an anti-plaque chewing gum might work just as well to kill bacteria in wounds. Hale envisioned integrating the synthetic molecule into a topical spray to treat patients in the field or loading it into a biomask for more definitive treatment after evacuation. Either way, he knew that if his team could keep biofilms at bay from the beginning, they could bring scarless healing within reach. 

As the DTRD team tested antimicrobial formulations, word spread that Hale was looking for engineers to make the biomask’s components. In 2010, an AFIRM partner introduced Hale to an electrical engineering researcher uniquely qualified for the job. Eileen Clements, who now directs research at the University of Texas at Arlington Research Institute, had been designing “smart bandages,” flexible polymers outfitted with miniature fluid-exchange devices that respond to bacterial toxins in wounds by releasing antibiotics to control infection. 

Clements had always focused on the mechanics of her devices, never imagining who might need them. But after talking with Hale and meeting Nelson, she didn’t have to imagine a need.

Soon Clements and her team took the first step toward creating a biomask, engineering small wound chambers that could eventually fit inside a face mask, simulating the negative pressure of a wound VAC. Tests in mice showed, as hoped, that the wound chambers prevented inflammation. Clements adapted the method to work on pigs so Hale’s team could compare the wound chambers with old-fashioned dressings and with conventional wound VACs. For these tests, they filled the chambers with a tetracycline solution, an antibiotic that also prevents inflammation. They treated laboratory pigs with each of the three methods, then after a week grafted the sites with split-thickness grafts much like Nelson’s. Over 120 days, Hale says, the sites treated with the antibiotic-filled wound chambers were as stable as a full-thickness graft. “It didn’t contract. It wasn’t a horrible color. It looked good,” he says. 

But that didn’t solve the problem of replacing lost facial skin without sacrificing patients’ already traumatized bodies.

In 2013, Hale met with scientists at Integra LifeSciences to describe his vision of the ideal skin substitute. The company agreed to share its formula so Hale and his collaborators could try to retool it to conform to the hills and hollows of a patient’s face. 

The reformulated Integra is still in a proof-of-concept phase and will need to undergo engineering and animal testing before it can be tested on humans. If it works as Hale hopes, surgeons could dispense with grafting new dermis. Then they would just need to replace the epidermis. One option Hale favors would be “spray-on skin,” which regenerates epidermal tissue from cells that naturally replenish skin. Developed in the 1990s by plastic surgeon Fiona Wood, head of the Burn Service of Western Australia, spray-on skin made international headlines in 2002 when she used it to treat survivors of terrorist bombings that killed 202 people in Bali.

Her technique involves taking a split-thickness biopsy about the size of a postage stamp (enough to treat an area up to 80 times as large) and soaking it for half an hour in an enzyme solution to extract “progenitor” cells, which promote healing and give skin color. The surgeon then sucks up the filtered cells with a syringe fitted with an atomizer and mists the wound. The new skin cells quickly adhere to the wound and proliferate to speed healing. Using such a small piece of skin might even allow Hale to take a sliver of scalp to better match the texture and hue of a patient’s face. 

Wood’s technology has been approved in Europe, Australia, Canada and China. In the U.S., AFIRM awarded Avita Medical nearly $2 million to compare spray-on skin with traditional grafts; the company is still recruiting patients and expects results in the next year or two.

Hale also saw potential in another major challenge in facial reconstruction: regenerating bone. More than 200,000 Americans undergo spinal surgery each year, supporting a multibillion-dollar market for bone regeneration products. Hale considered the wide interest in the technology as an opportunity to steer some of the research toward repairing facial bones torn apart by IEDs.

Restoring the complex architecture of the face and skull typically requires multiple operations that don’t always work, even when just a few of the 22 bones are broken. Restoring it when most of those bones sit pulverized within ravaged tissues has proved to be nearly impossible. 

From his first days at Brooke, Hale treated scores of patients with caved-in faces. Some were crushed from temple to chin. With such catastrophic bone injuries, he says, “we just can’t take what’s left over and reconstruct it.” Bones can grow new tissue after injury — that’s how fractures heal. But the body can’t regenerate a missing jaw. And titanium bone plates, which temporarily hold broken bones together during healing, were never meant to replace missing bones. Hale often had no choice but to ransack ribs, hips and legs for bone segments, just as generations of earlier surgeons had done. Over the course of as many as 100 operations, patients’ infections, scars and other complications multiplied.

Restoring recognizable features depended on re-creating the architecture of his patients’ facial skeleton, but doing that without cannibalizing their bodies begged for a different approach. With some patients, Hale and his team used a bone regeneration technology called Infuse Bone Graft, made by Medtronic. Designed for use in spinal fusion surgery of the lower back, Infuse consists of a titanium cage that houses a collagen sponge soaked in bone morphogenetic protein (BMP), a growth factor that signals bone-forming cells to produce new tissue. The cage is implanted between the vertebrae to maintain space for regenerating bone. 

Infuse’s primary virtue is that it doesn’t require harvesting healthy bone. But the size and shape of its titanium cage didn’t give Hale enough control to match patients’ missing bones. Worse, when surgeons started using Infuse to treat damaged neck vertebrae in 2008, the product caused dangerous swelling near the airway. Hale realized that shoving gobs of BMP into his patients’ lower jaws carried similar risks.

So he and AFIRM collaborator Scott Guelcher, a chemical engineer at Vanderbilt University, teamed up with scientists at Medtronic to devise a way to deliver BMP without worrying about suffocating patients. The team decided to replace the titanium cage and collagen sponge with a biodegradable scaffold that could also carry BMP, releasing it more slowly, like an extended time-release cold capsule. Experimenting with biodegradable materials that could hold their shape long enough to support bone growth without the titanium cage, Guelcher settled on a polyurethane composite that surgeons can sculpt like modeling clay to create scaffolds that heal bone. 

Hale’s group is now testing the new BMP scaffold in animals; clinical trials in humans are about five years away. But if the technique succeeds, he could start using BMP on his patients again — this time with far better results. And with a product that can create the curve of a jaw as easily as the top of a skull, he’s confident it won’t be long before he can use it to reconstruct the architecture of the face with bones that move the way they were meant to. 

Restoring the architecture of the face and skull typically requires multiple operations that don't always work, even when just a few of the 22 bones are broken.

Regenerating skin and bone is hard enough. Regenerating the intricate web of muscles and nerves that surround them is a challenge Hale believes regenerative medicine is unlikely to conquer anytime soon. At present, he sees only one way to give patients functional tissue capable of sensory perception: face transplants. 

In December 2008, AFIRM collaborators at the Cleveland Clinic led by Maria Siemionow performed the first near-total face transplant in the U.S. The 40-year-old patient, Connie Culp, had lost her nose, an eye, eyelids, upper jaw, lip and palate after her estranged husband shot her in the face. The transplant achieved what nearly 30 reconstructive surgeries had not, allowing Culp to eat and breathe normally again and to leave her house without fear of cruel taunts.

Hale had long championed face transplants as an option for treating blast injuries. Now he had direct access to surgeons who could perform them. But he knew military leaders were averse to subjecting veterans to the risk of a lifetime of immunosuppressants. After Culp’s transplant, Hale worked with Siemionow and her team to identify other immune-suppression options.

One promising approach focused on a drug called TOL-101, which inhibits the immune cells responsible for rejecting transplanted tissue. In a 2003 study in rats, Siemionow had shown that TOL-101 allowed surgeons to transplant face and scalp tissue from one animal to another. She later discovered that administering TOL-101 for as little as a week could prevent rejection. The drug works faster than other immunosuppressants, and so carries less risk.

Hoping these efforts to minimize transplant surgery’s risks would reassure his bosses, Hale in 2009 urged the AFIRM board of directors to include transplant medicine in their program. Thomas Starzl, the pioneering University of Pittsburgh surgeon who performed the first successful liver transplant in 1967, happened to be at that board meeting. Hale couldn’t believe his luck when the father of transplant medicine stood up and declared, “Transplant medicine is regenerative medicine.” 

By the end of 2009, the Army awarded $1.4 million to the Cleveland Clinic and another $3.4 million in grants to Brigham and Women’s Hospital in Boston, which completed the second full-face transplant in the U.S. in April 2011. Cleveland Clinic surgeons launched a trial to test the dose, effectiveness and safety of TOL-101 on 33 kidney transplant patients. In April of this year, the team reported that patients responded well, with no serious complications, suggesting the therapy might also work for face transplants. 

Pentagon-funded clinical trials for face transplants are now underway at the Cleveland Clinic and Brigham and Women’s Hospital. Last year AFIRM launched its second initiative with $75 million to fund the procedures.The $300,000-plus operation takes more than 20 hours and requires a team of some 50 experts. Only 28 have been performed in the world since the first in 2005. Hale’s wounded soldiers could double the tally before the decade is out. So far, he’s helped identify 13 candidates for the Cleveland Clinic study, but he says at least 200 veterans could be eligible for face transplants.

And so what once seemed a distant dream to help featureless veterans return to the society that sent them to war now hovers on the horizon. If Hale’s research proceeds according to plan, within five years he’ll have a biomask and custom skin substitutes to restore melted flesh. He’ll have bone-regenerating compounds to re-create the skeletal foundation of smashed faces. And, for those whose injuries defy these technologies, he’ll be able to say, finally, that the Army can give them a whole new face.

Not all of his patients will embrace the idea of adopting someone else’s face. Nelson, for one, has no interest in a face transplant. After 43 operations, he told Hale he’d had enough. His eyes — one real, one prosthetic — still sit wide apart and slightly askew, his once-boyish grin hobbled by scars. He doesn’t mind.

But Nelson, who believes he was spared to help wounded vets adjust to their new lives, does want to see better outcomes for other victims of severe trauma. So he’ll continue to serve on the science committee for Hale, whose perseverance, Nelson says, “will put him in the history books.”

And while the Army looks for new ways to protect its soldiers, the face will probably always remain vulnerable to the worst traumas of war. But soon, thanks largely to Hale’s efforts, when Todd Nelson’s wounded brothers and sisters arrive at Brooke, 21st-century medicine will be waiting.

[This article originally appeared in print as "Face of Hope."]