Facial Transplantation Pushes Beyond Limits of Reconstruction

Biomedical and clinical advances are offering surgeons unprecedented opportunities to provide high-quality functional and aesthetically pleasing outcomes for patients with severe injuries. There are limits, however, to what can be achieved with a purely reconstructive approach.

For individuals who have suffered high-grade facial injuries or disfigurement, lost a major part of their face, and experience extreme functional limitations, an option that is increasingly becoming feasible is facial transplantation.

Surgeons have been slowly but steadily amassing experience and outcomes data on face transplants—once a procedure that seemed more science fiction than clinical reality—since the first successful operation took place in 2005.

Although only 54 face transplants have been completed around the world over the past 20 years, the results of these limited cases have been largely positive. Patients are regaining functionality of their damaged facial subunits, with some limitations, and aesthetic outcomes are constantly improving.^1,2

Because of the small number of completed facial transplants, each case represents a significant learning opportunity for surgeons and the transplant care team.

Broad Spectrum of Indications

As with a solid organ transplant, the process of a patient receiving a face transplant is extensive and lengthy, but the unique elements of facial transplant require additional layers of preparation.

A face transplant is a form of vascularized composite allotransplantation (VCA), requiring multiple tissue types including skin, fat, muscle, bone, nerves, and blood vessels.³

As such, “every case is absolutely unique, because the injury and what needs to be replaced is unique,” according to Bruce E. Gelb, MD, FACS, a transplant surgeon and associate professor in the Department of Surgery and Transplant Institute at New York University (NYU) Grossman School of Medicine in New York City, who has served as a medical team leader for NYU Langone’s high-profile face transplants for the last decade.

Due to the limited data points on the technique, however, the indications to pursue a transplant are not firmly set and are up to a surgeon to decide.

“It starts with evaluating the surgical defect, and the team has to agree whether it is something that can be managed conventionally or not,” said Bohdan Pomahac, MD, the Frank F. Kanthak Professor of Surgery (Plastics) and chief of the Division of Plastic and Reconstructive Surgery at the Yale School of Medicine in New Haven, Connecticut.

Dr. Pomahac also led the first face transplant performed in the US in 2011 while he practiced at Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts; he has led the most face transplants of any surgeon in the world.

Beyond the surgical and medical indications, equally important are considerations into a patient’s support system, as well as their economic and psychosocial position.

“A face transplant requires that the patient has adequate support. Through a face transplant, we often convert patients who are relatively physically healthy, despite their severe deformity, into somebody who, due to chronic immunosuppression, requires frequent physician visits and follow-ups,” Dr. Pomahac said, which means a significant outlay of time for caregivers and money for copays, transportation, housing, and so on.

All organ transplant recipients work with social workers and psychiatrists to ensure they have the support and cognitive ability to receive the transplant and understand the steps needed to help ensure its function and their health. Face transplant recipients, however, are in the unique position of receiving a transplant with a strong visual component that will influence not only their interactions with the outside world, but also their internal world.

“What I discuss with the patients is that when they come out of surgery, it may rekindle the emotional trauma from their original injury, because they may not be able to see, and they won’t be able to talk or eat at first,” Dr. Gelb said. “They’re going to need to relearn a lot of things during the recovery, and they likely will be in the hospital for a long time.”

Because the transplant recipients will need to be on immunosuppressive medication for the rest of their lives, they cannot opt out of their healthcare. Immunosuppression will almost certainly shorten a recipient’s lifespan and cause medical complications, putting them at risk for diabetes, kidney disease, high blood pressure, and infections.

It is critical that patients understand that a face transplant represents a tradeoff in form and function against overall health. The ongoing logistical and emotional burden of a face transplant requires a strong personal will and commitment to success, as well as long-term mental health support.⁴

Rigorous Preparations

Once the recipient and care team are in accord on pursuing a face transplant, the significant work of preparing for the complex, lengthy procedure begins in earnest.

“We start by doing rehearsals in the OR on research cadavers. We'll have two rooms, and there'll be two cadaver heads, and one team will be removing the tissue to be transplanted, and the other team will be practicing removing the injured tissue in preparation for transplant,” Dr. Gelb said.

One of the significant developments that has aided in these VCAs is increasingly specific advanced imaging and surgical guides, he added. CT imaging provides clear imaging of the bones, magnetic resonance neurography shows nerves, and venograms, arteriograms, and angiograms highlight vascular system of recipients, allowing surgeons to create a plan showing how the heterogenous tissues will be connected.

After months of preparation and rehearsals based on the recipient’s case profile, once a donor face becomes available, the process accelerates quickly.

“We work up the donor similarly—very rapidly—and then from that, we know we're going to make our bony cuts on both donor and recipient, and we know the vascular anatomy necessary for a successful transplant,” Dr. Gelb said.

But because no two faces are the same and everything must align correctly, part of the computerized surgical plan is creating 3D-printed guides. These are pieces of plastic that snap on so that surgeons know where to make the osteotomies on the donor and recipient.

“The recipient process is completed in advance. On the donor side, we perform the imaging, it gets uploaded, and then the 3D printing starts right away so that we have those cutting guides within a couple hours, and we can proceed with the surgery,” Dr. Gelb said.

As an example of the utility of presurgical planning, Dr. Gelb described the preparation for a patient who underwent a combined partial-face and whole-eye transplant in May 2023 at NYU Langone.⁵

The 46-year-old patient experienced a high-voltage burn, where electricity entered the back of his head and conducted through the front. Resultantly, he had severe disfigurement on most of his face and lost his left eye. His mouth was fixed open, so he couldn’t eat or drink and speech was severely affected, and his nose was lost.

There was no conventional reconstruction approach that could come close to what a face transplant offered and, ultimately, achieved, Dr. Gelb said.

Showing how all severe facial injuries, underlying anatomy, and corrective options were unique, it was determined during the planning process that the patient would be best served with a whole-eye transplant—a historic first.

“Because it was an electrical injury that affected deep tissue and bone, we needed to transplant that whole area of the face—but there was a fistula between the eye socket and his nasopharynx. So, we had to fill that space with a transplant, and the only way to do that was to transplant the eye at the same time,” Dr. Gelb said.

“We didn't start off intending to perform an eye transplant, but we had to replace the orbital box, and the safest way to do that is with the eyeball,” he explained.

The patient was on the transplant list for about 4 months before a suitable donor was identified, but Dr. Gelb and the transplant team had started preparing before he was formally placed on the list. At least once a month, the surgical teams performed a rehearsal up until the time they did the transplant, which made for a total of 15 rehearsals over a yearlong period.

OR Advances in Technology and Teamwork

The intensive preoperative phase leads to a day of surgery that, while notably long, should proceed as planned. What drives an efficient and successful day of surgery are advances in technology as well as a strong, multidisciplinary team.

“Compared to 10 or 20 years ago, we do have more precise technologies, and robotics is one of them. Microsurgical tools allow us to perform the same task with greater accuracy, whether it's connecting the small blood vessels or nerve branches,” Dr. Pomahac said.

“In the big picture, because there are so few of these operations, we have learned how to manage individual tissues to some extent. What do we do with glands that are in the allograft? How do we connect the nerves? How did we do in dissecting the donor’s and recipient’s bones?” he added.

These multiple tissue types necessitate a multidisciplinary team while in the OR, all applying their specialized care—care that, taken in isolation, isn’t necessarily groundbreaking.

“It's very much a team of teams approach. Many of the individual things we're doing are not brand new,” Dr. Gelb said. “It's not like xenotransplantation, where we're transplanting a pig organ into someone. It's using highly specialized and well-known areas within different specialties and having them work together.”

Members of the surgical team alone may include plastic surgeons, craniofacial surgeons, microvascular free flap surgeons, oral surgeons for dentistry, and ophthalmologists if the eye is involved, in addition to an extensive nursing and technical support staff.

The multidisciplinary nature of the team extends far beyond the OR, including psychology, speech-language pathology, neurology, physical therapy, skin pathology, and radiology, as well as ethicists and patient navigators.⁶

The team effort is greatly enhanced by incorporating known techniques for improving team performance.

“We leverage a lot of high-reliability organization foundations in the OR, including deference to expertise. The surgical team is scrubbed in and focused, so we have people in the room who are going to point out sterility, the need to change your gloves, and who should move where. It's like air traffic control to ensure safety,” Dr. Gelb said.

This stands in stark contrast to historical conceptions of OR leadership, where providing suggestions to the operating team may not have been tolerated by the lead surgeon.

“We intentionally have things set up so that we all acknowledge that someone else is going to see something, and they're saying something if needed,” he said.

But because facial transplant science and processes are still in their relative infancy and unique in several ways, there remains a need to improve the intraoperative experience for surgeons.

“I think what we still lack is a two-team approach that exists in other types of transplant surgery—a recovery team and a transplanting team. Right now, it's still one team, and these 24-hour-long operations are exhausting,” Dr. Pomahac said.

Addressing Rejection

Effective pre- and intraoperative phases of any surgery are fundamental to long-term success, but facial transplantation presents unique challenges and opportunities with immunosuppression, and the field has seen steady advances in recent years.

“When the field started 20 years ago, transplant teams argued that for a non-lifesaving transplant, you shouldn't need as much immune suppression. The focus of the field was minimizing or potentially eliminating immune suppression altogether for face transplants,” Dr. Pomahac said.

In a face transplant patient, the supposition at the time was that the rejection would be immediately noticed—unlike a solid internal organ like a kidney or heart—and that greater risks could be taken, such as single-agent therapy. This approach was not successful in solid organ transplantation, primarily because kidney rejection may only be discovered weeks or months after it starts.

Dr. Pomahac explained that the first line of rejection is in the T lymphocytes, and it's only after the rejection goes on for a while and the antigens and targets cells are identified that the B-cell lymphocytes are activated to destroy foreign tissue. However, they also create the memory cells that, like a vaccine, will “remember” and increasingly respond to the foreign tissue. A critical mass of memory cells can lead to loss of the transplant.

If patients let their physicians know they are having an issue—and can tell due to their face swelling or turning red—early intervention can be offered in T-phase rejection.

“What we have learned over the years is that to avoid most of the complications, the best approach is to immunomodulate by putting patients on at least three, but potentially four immunosuppressive medications,” Dr. Pomahac said.

While this is a significant amount of immunosuppression, care teams can lower or adjust the dosages over time to minimize the side effects.

“In my mind, that's a huge accomplishment, because we are now learning that these transplants can survive for many years. The oldest face transplant is one of my patients, and she's out 14 and a half years without much sign of chronic rejection,” he said.

Still, the possibility of rejection is a clinical reality even years after an initial successful surgery, and the care team will need to provide regular follow-up care to guard against it.⁷

Facing the Future

Dr. Gelb noted that his most recent patient, the whole-eye and partial-face transplant recipient, has made a strong recovery, restoring much function of his mouth and nose, as well as sensation to the transplanted tissue.

In addition, the whole-eye transplant has proven to be a remarkable scientific achievement that will provide the foundation for new research going forward. Previously, the widely accepted understanding was that once an optic nerve is cut, the eye will shrivel and lose form. However, the eye has maintained its health and shape, and the retina has even shown reactivity to light, though the sensation did not pass on to the brain. The optic nerve even showed early signs of trying to regenerate.

“He will never get vision, and the optic nerve has regressed on imaging since that time, but we saw some progress in the first couple months, and there's going to be all sorts of research that comes out of that for the feasibility of eye transplant in the future,” Dr. Gelb said.

While this is an exciting time for the science and clinical outcomes of face transplantation, the immediate concerns for the future are more mundane, but no less critical.

First, funding is an issue. As stated earlier, these are expensive operations, and they entail permanent costs to patients and payers due to immunosuppression and ongoing medical needs.

But current funding for the operations comes from government grants or one-off approvals from insurers. To have facial transplantation covered as a standard of care, it will need to move from being classified as experimental. To that end, stakeholders have come together to create standardized principles for the field.

Leadership in facial transplants were told by payers that they “need to know consensus on indications, consensus on outcomes, and the cost,” Dr. Pomahac said.

Efforts to create international standards for face transplants have already seen success,⁸ and US-based standards are now progressing as well.

The US Department of Defense (DoD) tasked the National Academies with creating standards for face and hand transplants—another type of VCA. The group published a report outlining principles and a framework for standardizing protocols in these VCA transplants, which was the foundation for the creation of the Clinical Organization Network for Standardization of Reconstructive Transplantation (CONSORT).⁹

Created at the request of the DoD, Dr. Pomahac is a lead researcher for CONSORT using data from every major face transplant center in the US. 

“The goal of phase one is to develop the standards on indications, immune suppression management, outcomes, and then based on that, run a cohesive clinical trial on face and hand transplant,” Dr. Pomahac said.

At the conclusion of the trial, the hope is that the data provided to insurance companies will allow the procedures to be covered alongside other transplant surgeries. The research derived from the trial already is credited with leading to the world’s first face and bilateral hand transplant,¹⁰ which was led by Eduardo D. Rodriguez, MD, DDS, FACS, director of the NYU Langone Face Transplant Program and the NYU Langone Laura and Isaac Perlmutter Cosmetic Plastic Surgery Center. Dr. Rodriguez is the lead surgeon on face transplants performed at NYU Langone.

The second challenge is related to referrals for face transplants. Many surgeons, much less patients, are not aware that a facial transplant is even a possibility for a severe injury or disfigurement, Dr. Gelb said.

“If you think of it on the continuum of treating devastating facial injuries, a face transplant is the last resort. What tends to happen is that patients are treated for an injury in a trauma center, they're stabilized, and then there are many attempts at reconstructive surgery—all of which makes it even harder to do the transplant, because you need to undo all that work,” he said.

Early referral to face transplant centers or surgeons then becomes critically important to ensure that the appropriate patient has access to the care when it would make the most impact.

As Dr. Gelb noted, his team often is approached by potential candidates based on self-referrals.

“They might see an article on a face transplant in People magazine, and then they call the center. Needless to say, your primary referral source should not be a magazine,” he said, adding that members of the field seek to establish a formal referral network accessible to surgeons and patient alike.

Ultimately, in these still early days of remarkable growth and achievement in facial transplantation, the goal is to make severely injured patients aware that this option exists, and that it can profoundly affect their lives by returning them to acceptable form, adequate function, and a normal life.

“We as surgeons say this is a life-changing procedure, not necessarily a lifesaving one,” Dr. Gelb said. “But almost all the patients who have a face transplant say, no, this is lifesaving, because they were not really living with the injury they had.”

Matthew Fox is the Digital Managing Editor in the ACS Division of Integrated Communications in Chicago, IL.

References

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9. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Board on Health Care Services; Committee on Principles and Framework to Guide the Development of Protocols and Standard Operating Procedures for Face and Hand Transplants, Cooper R, Kizer KW, eds. Advancing Face and Hand Transplantation: Principles and Framework for Developing Standardized Protocols. Washington (DC): National Academies Press (US); May 28, 2025.
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