Face Transplantation Research Articles

Face transplantation for massive mandibular defects: considerations for allograft design and surgical planning

Modern face transplant techniques have advanced to allow for the transfer of vascularized skeletal components in addition to overlying soft tissue. This represents significant opportunity for individuals with mandibular defects that are not amenable to traditional reconstruction. Care must be taken when planning and executing transplants with these complex grafts, as satisfactory functional and aesthetic outcomes rely on achieving proper spatial relationships between the mandible, skull base, and midface. Which donor skeletal elements are included in the allograft and how they are harvested are important considerations in this planning and are associated with controversy. To optimize outcomes in the reconstruction of single-jaw defects, some advocate for transplantation of only the affected jaw while others support bimaxillary transplantation. Clinical evidence in this debate is not conclusive at this time. In current practice, including donor dentoalveolar anatomy by utilizing a bilateral sagittal split osteotomy of the mandible is favored to optimize outcomes such as dental occlusion. It has been suggested that harvesting the mandible at the level of the condyle or even the temporal bone may also be possible and may improve temporomandibular joint-related outcomes. Despite encouraging preclinical evidence, these strategies remain controversial. After allograft design, successful mandibular reconstruction with face transplantation relies on surgical precision in the donor and recipient procedures. Computerized surgical planning, computer-aided design and manufacturing, and intraoperative navigation are technologies currently in use to mitigate operative complexity. Results in both cadaveric and clinical face transplantations suggest these technologies are reliable and beneficial, although some room for improvement remains.

Recognizing Emotional Expression as an Outcome Measure After Face Transplant

Limited quantitative data exist on the restoration of nonverbal communication via facial emotional expression after face transplant. Objective and noninvasive methods for measuring outcomes and tracking rehabilitation after face transplant are lacking. To measure emotional expression as an indicator of functional outcomes and rehabilitation after face transplant via objective, noninvasive, and nonobtrusive software-based video analysis. This single-center case-control study analyzed videos with commercially available video analysis software capable of detecting emotional expression. The study participants were 6 patients who underwent face transplant at Brigham and Women's Hospital between April 2009 and March 2014. They were matched by age, race/ethnicity, culture, and sex to 6 healthy controls with no prior facial surgical procedures. Participants were asked to perform either emotional expressions (direct evaluation) or standardized facial movements (indirect evaluation). Videos were obtained in a clinical setting, except for direct evaluation videos of 3 patients that were recorded at the patients' residences. Data analysis was performed from June 2018 to November 2018. The possibility of detecting the emotional expressions of happiness, sadness, anger, fear, surprise, and disgust was evaluated using intensity score values between 0 and 1, representing expressions that are absent or fully present, respectively. Six patients underwent face transplant (4 men; mean [SD] age, 42 [14] years). Four underwent full face transplants, and 2 underwent partial face transplants of the middle and lower two-thirds of the face. In healthy controls, happiness was the only emotion reliably recognized in both indirect (mean [SD] intensity score, 0.92 [0.05]) and direct (mean [SD] intensity score, 0.91 [0.04]) evaluation. Indirect evaluation showed that expression of happiness significantly improved 1 year after transplant (0.04 point per year; 95% CI, 0.02 to 0.06 point per year; P = .002). Expression of happiness was restored to a mean of 43% (range, 14% to 75%) of that of healthy controls after face transplant. The expression of sadness showed a significant change only during the first year after transplant (-0.53 point per year; 95% CI, -0.82 to -0.24 point per year; P = .005). All other emotions were detectable with no significant change after transplant. Nearly all emotions were detectable in long-term direct evaluation of 3 patients, with expression of happiness restored to a mean of 26% (range, 5% to 59%) of that of healthy controls. Partial restoration of facial emotional expression is possible after face transplant. Video analysis software may provide useful clinical information and aid rehabilitation after face transplant.

Spotlight in Plastic Surgery: January 2020

Spotlight in Plastic Surgery: January 2020

Development of a New Large-Animal Model for Composite Face and Whole-Eye Transplantation: A Novel Application for Anatomical Mapping Using Indocyanine Green and Liquid Latex.

Recent advances in the field of vascularized composite allotransplantation have revolutionized reconstructive surgery and demonstrated opportunity for restoration of orbital content and perhaps vision. The development of an animal model that would facilitate study of surgical technique, nerve regeneration, vision restoration, and immunosuppression is needed. The aim of this study is to describe three different large-animal cadaveric models suitable for composite face and whole-eye transplantation. In addition, the authors introduce a novel colored liquid latex and indocyanine green mixture for vasculature identification and visualization. The authors studied three different flap designs using cadaveric Yorkshire swine and modified them for face and whole-eye transplant harvest. Flaps harvested included a chimeric flap, a monobloc flap, and a bipedicled free flap. The authors injected selected vasculature with colored latex to better delineate vascular anatomy supplying the orbit and face. Indocyanine green was added to the latex solution to allow for visualization of the vascular supply using near-infrared imaging. Colored latex and indocyanine green injections were successfully visualized in all cadaveric dissections. All three modified flap designs showed a well-defined and consistent vascular network within each face and whole-eye transplantation flap using laser-assisted near-infrared imaging. The authors present the feasibility of composite face and whole-eye transplantation models using a novel mixture of liquid latex and indocyanine green in a porcine cadaver. Further study in large animals is needed to appraise the surgical feasibility of this procedure and potential for clinically relevant outcomes, including vision restoration. The authors believe this study establishes a foundation for translation into live animal models for optic nerve regeneration.

Перекрестная пересадка комбинированного лицевого трансплантата в эксперименте на биообъектах

Facial graft transplantation remains the operation of choice for patients with extensive tissue defects in the maxillofacial region. This study aimed to set up an experiment on biological objects, develop and test a combined facial graft cross-transplantation technique, select the anesthetic aid allowing to reduce the risks of perioperative complications, improve survivability of the subjects by reducing the duration of surgical intervention, develop a postoperative therapy and rehabilitation protocol, assess detection of an acute rejection reaction and develop the immunosuppressive therapy protocol. We conducted three series of facial graft transplantation surgeries on 26 minipigs and tested the typical component combinations and flap designs. At all stages of the experiment, we managed to have the subjects surviving for over 30 days without disrupting their vital functions. The immunosuppression procedure was developed and tested. The chosen technique allows transplanting two grafts within a single surgery on one pair.

Defining chronic rejection in vascularized composite allotransplantation-The American Society of Reconstructive Transplantation and International Society of Vascularized Composite Allotransplantation chronic rejection working group: 2018 American Society of Reconstructive Transplantation meeting report and white paper Research goals in defining chronic rejection in vascularized composite allotransplantation.

Objectives:This report summarizes a collaborative effort between the American Society of Reconstructive Transplantation and the International Society of Vascularized Composite Allotransplantation to establish what is known about chronic rejection in recipients of vascularized composite allografts, with an emphasis on upper extremity and face transplants. As a picture of chronic rejection in hand and face vascularized composite allografts emerges, the results will be applied to other types of vascularized composite allografts, such as uterine transplantation.Methods:The overall goal is to develop a definition of chronic rejection in vascularized composite allografts so that we can establish longitudinal correlates of factors such as acute rejection, immunosuppressive therapy, de novo donor-specific antibody and trauma/infection and other external factors on the development of chronic rejection. As Dr Kanitakis eloquently stated at the 2017 International Society of Vascularized Composite Allotransplantation meeting in Salzburg, “Before we can correlate causative factors of chronic rejection, we have to define what chronic rejection in VCA is.”Results:The first meeting report was presented at the sixth Biennial meeting of the American Society of Reconstructive Transplantation in November 2018. Based on collaborative efforts and descriptions of clinical cases of chronic rejection in vascularized composite allograft recipients, a working definition of chronic rejection in vascularized composite allografts with respect to overt functional decline, subclinical functional decline, histologic evidence without functional decline, and normal allograft function in the absence of histologic evidence of chronic rejection is proposed.Conclusions:It is the intent of this collaborative working group that these working definitions will help to focus ongoing research to define the incidence, risk factors and treatment regimens that will identify mechanisms of chronic rejection in vascularized composite allografts. As with all good research, our initial efforts have generated more questions than answers. We hope that this is the first of many updates.

Face transplantation: general review and long-term management of the dental patient.

Facial allotransplantation (FA) is an emerging alternative modality following severe loss of hard and soft tissues. Although there are vast numbers of publications on the surgical aspects of this technique, limited information is available in the literature with regard to the long-term dental care of affected patients following postoperative stabilization and return to their locally based clinical milieu. The objective of this report is to review patient demographics, etiologies, structural graft components, immunosuppressive strategies, donor tissue pathogenicity, neurologic recovery, potential complications, and present clinical guidelines for dental management. Additionally, a brief discussion of the preparation of the donor mask, and cutaneous and intraoral images of allograft rejection have been provided.

Application of Adipose Stem Cell Glue in Facial and Breast Plastic

Objective: This study was aimed to evaluate the effect of adipose stem cell gel (SVF-gel) in facial and breast plastic surgery. Methods: A retrospective study of 60 young patients who underwent facial and breast fat transplantation from January 2017 to May 2019 in the Plastic Surgery Department of Yuebei People’s Hospital (SVF-gel transplantation group 30 cases, traditional Coleman fat transplantation group 30 cases), and analyze the patient's curative effect. Results: 60 patients were about 35 years old (34.66±8.76 years old in the SVF-gel group, 35.25±9.01 in the traditional Coleman fat transplantation group). The BMI of the SVF-gel group was 24.36±4.02, while that of the traditional Coleman fat transplantation group was 25.01±4.05. The follow-up time of 60 patients was about 8 months. The results showed that the fullness and contour of the face and breast of all patients were improved to varying degrees compared with preoperatively. The satisfaction degree of SVF-gel transplantation group was higher than that of traditional Coleman fat transplantation group. Conclusion: SVF-gel has obvious advantages over traditional fat transplantation in volume filling and rejuvenation of the face and breasts.

The Centrality of Emotional and Quality of Life Outcomes in the Public Perception of Face Transplantation

The Centrality of Emotional and Quality of Life Outcomes in the Public Perception of Face Transplantation

Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation.

The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation-free conditioning protocol that combines anti-lymphocyte serum (ALS), tacrolimus, and cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) with adipose-derived stromal cells (ASCs) to allow VCA survival without long-term systemic immunosuppression. Full-mismatched rat hind-limb-transplant recipients received tacrolimus (0.5mg/kg) for 14days and were assigned to 4 groups: controls (CTRL) received no conditioning; ASC-group received CTLA4-Ig (10mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1×106 iv, POD 2, 4, 7, 15, 28); the ASC-cyclophosphamide (CYP)-group received CTLA4-Ig, ASC plus cyclophosphamide (50mg/kg ip, POD 3); the ASC-ALS-group received CTLA4-Ig, ASCs plus ALS (500µL ip, POD 1, 5). Banff grade III or 120days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection-free VCA survival was 28days in CTRL (n=7), 34 in ASC (n=6), and 27.5 in ASC-CYP (n=4). In contrast, ASC-ALS achieved significantly longer, rejection-free VCA survival in 6/7 animals (86%), with persistent mixed donor-cell chimerism, and elevated systemic and allograft skin Tregs , with no signs of acute cellular rejection. Taken together, a regimen comprised of short-course tacrolimus, repeated CTLA4-Ig and ASC administration, combined with ALS, promotes long-term VCA survival without chronic immunosuppression.

Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation

For individuals who sustain devastating composite tissue loss, vascularized composite allotransplantation (VCA; e.g., hand and face transplantation) has the potential to restore appearance and function of the damaged tissues. As with solid organ transplantation, however, rejection must be controlled by multidrug systemic immunosuppression with substantial side effects. As an alternative therapeutic approach inspired by natural mechanisms the body uses to control inflammation, we developed a system to enrich regulatory T cells (Tregs) in an allograft. Microparticles were engineered to sustainably release TGF-β1, IL-2, and rapamycin, to induce Treg differentiation from naïve T cells. In a rat hindlimb VCA model, local administration of this Treg-inducing system, referred to as TRI-MP, prolonged allograft survival indefinitely without long-term systemic immunosuppression. TRI-MP treatment reduced expression of inflammatory mediators and enhanced expression of Treg-associated cytokines in allograft tissue. TRI-MP also enriched Treg and reduced inflammatory Th1 populations in allograft draining lymph nodes. This local immunotherapy imparted systemic donor-specific tolerance in otherwise immunocompetent rats, as evidenced by acceptance of secondary skin grafts from the hindlimb donor strain and rejection of skin grafts from a third-party donor strain. Ultimately, this therapeutic approach may reduce, or even eliminate, the need for systemic immunosuppression in VCA or solid organ transplantation.

Ethical Issues Posed by Face Transplants

A face transplant is as challenging a surgical procedure as any patient can undergo. In this introduction I present the medical aspects of this surgery, the profound ethical issues it raises, and optimal interventions that clinicians can pursue to help these patients and their loved ones. I then discuss how to help other kinds of patients and loved ones who confront similar stresses. I end by presenting a goal that author Sharrona Pearl puts forth after she studied many face transplant patients. The efforts she urges should maximize our capacity to see face transplant patients-and anyone-as they are, as opposed to how they look.

Blood proteome profiling using aptamer-based technology for rejection biomarker discovery in transplantation

Face transplantation is a promising solution for patients with devastating facial injuries who lack other satisfactory treatment options. At the same time, this type of transplantation is accompanied with high risks of acute transplant rejection. The limitations of traditional skin biopsy and the need to frequently monitor the condition of face transplant call for less invasive biomarkers to better diagnose and treat acute rejection. Discovery of peripheral serum proteins accurately reflecting the transplant status would represent a reasonable solution to meet this demand. However, to date, there is no clinical data available to address the feasibility of this approach. In this study, we used the next generation aptamer-based SOMAscan proteomics platform to profile 1305 proteins of peripheral blood serum in twenty-four samples taken from 6 patients during no-rejection, nonsevere rejection, and severe rejection episodes. Also, we provide a detailed description of biosample processing and all steps to generate and analyze the SOMAscan dataset with hope it will assist in performing biomarker discovery in other transplantation centers using this platform.

MMP3 Is a Non-invasive Biomarker of Rejection in Skin-Bearing Vascularized Composite Allotransplantation: A Multicenter Validation Study.

Background: There is unmet need for non-invasive immunomonitoring to improve diagnosis and treatment of acute rejection in vascularized composite allotransplantation (VCA). Circulating matrix metalloproteinase 3 (MMP3) was described as a candidate non-invasive biomarker to predict treatment response to acute rejection in clinical VCA. However, larger validation studies are yet to be reported to allow for more definitive conclusions.Methods: We retrospectively measured MMP3 levels using ELISA in a total of 140 longitudinal serum samples from six internal and three external face transplant recipients, as well as three internal and seven external upper extremity transplant recipients. The control groups comprised serum samples from 36 kidney transplant recipients, 14 healthy controls, and 38 patients with autoimmune skin disease. A linear mixed model was used to study the effect of rejection state (pre-transplant, no-rejection, non-severe rejection (NSR), and severe rejection) on MMP3 levels.Results: In VCA, MMP3 levels increased significantly (p < 0.001) between pre- and post-transplant no-rejection states. A further increase occurred during severe rejection (p < 0.001), while there was no difference in MMP3 levels between non-severe and no-rejection episodes. A threshold of 5-fold increase from pre-transplant levels could discriminate severe from NSR with 76% sensitivity and 81% specificity (AUC = 0.79, 95% CI = 0.65–0.92, p < 0.001). In kidney transplantation, the MMP3 levels were significantly (p < 0.001) elevated during antibody-mediated rejection but not during T-cell mediated rejection (TCMR) (p = 0.547). MMP3 levels in healthy controls and autoimmune skin disease patients were comparable with either pre-transplant or no-rejection/NSR episodes of VCA patients.Conclusion: The results of this study suggest that serum MMP3 protein is a promising marker for stratifying patients according to severity of rejection, complementary to biopsy findings.

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

117.2: Organ donation organization preparation for facial transplantation: The Transplant Québec experience.

Background: Globally, there have been 43 face transplants performed since the first one in France, 2005. The preparation required to proceed towards vascularized composite allotransplant donation is dynamic and complex. Three years of collaborative, multi-disciplinary planning were required prior to the completion of the first facial transplantation in Canada and the Commonwealth. Methods: Transplant Québec worked in a coordinating role with multiple teams and agencies, including the transplant team, Hôpital Maisonneuve-Rosemont (located in Montréal), Health Canada, and the Ministry of Health of Québec. While developing a standard operating procedure (SOP), Transplant Québec looked to other jurisdictions which had already successfully performed this highly sophisticated procedure including the University of Maryland in Baltimore, Maryland, and New York University. Using these existing SOPs as a model, a specific SOP, tools and manuals were created and adapted to educate the Transplant Québec clinical staff regarding donor eligibility evaluation and the, logistics of procurement procedure. Concurrently, the ethics committee of Transplant Québec and the hospital research ethics board reviewed the research protocol, to ensure that the donor families were aware that images from the transplant recipient will presented to the media, and to ensure that no lifesaving organs were put at risk during the procurement. Results: Transplant Québec deployed the SOP for facial donation in February 2018. The protocol was executed by the donor coordinators who displayed interest in the project and who helped outline throughout the 3-year process. In accordance with ethics recommendations and the new SOP, facial transplantation was successfully performed in May 2018 during a 30 hours operation. Thoracic and abdominal organs were also successfully recovered and transplanted from the same donor. Coordinators approached the family in two distinct steps: first general consent was obtained for organ donation from a patient determined brain death, then separate consent was obtained for facial recovery and transplantation. The transplant surgeon was then called to the bedside to perform a bone, tooth and skin tone evaluation. The donor family was given guidance and support regarding media exposure. Conclusions: Successful facial transplantation requires focused and strong collaboration of all shareholders. While the medical, ethical and logistic issues were difficult to overcome, the result for the donor family, the recipient and the interest generated in the donation and transplantation system will generate benefits for years to come.

How to Integrate Lived Experience Into Quality-of-Life Assessment in Patients Considering Facial Transplantation.

Facial transplantation has gained increasing acceptance as a treatment option to improve quality of life (QoL) for persons suffering from severe facial disfigurement. Despite its growth, the field has yet to establish a consistent approach to assessing QoL in face transplant candidates and recipients that includes integration of meaningful patient-reported outcomes. The published literature suggests that face transplant programs currently use a wide variety of assessment tools and strategies. Moreover, confusion remains as to how best to weigh patients' lived experiences and incorporate them into QoL assessments. Qualitative research can illuminate the dimensions of QoL that are meaningful to face transplant candidates and recipients. Coupled with collaboration and data sharing across face transplant programs, qualitative research will help to bring conceptual clarity and transparency to the assessment process.

Magnetic Resonance Imaging Volumetry of Facial Muscles in a Face Transplant Recipient.

Summary:Face transplantation has evolved into a viable reconstructive option for patients with extensive facial disfigurement. Because the first face transplant procedure was described in 2005, the safety and feasibility of the procedure have been validated, and the focus of the field has shifted toward refining functional and esthetic outcomes. Recovery of muscle function following facial transplantation is critical to achieving optimal facial function and restoring facial expression. Assessment of facial muscle function in face transplant recipients has traditionally relied on clinical evaluation. In this study, we describe longitudinal changes in facial muscle volumes captured through quantitative magnetic resonance imaging in a face transplant recipient and compare these findings with functional outcomes evaluated through clinical assessment.

322.5: Impact of a face procurement on intermediate solid organ outcomes.

Background: With the advent of vascularized composite tissue allotransplantation (VCA) there has been a concern regarding its potential to negatively impact the recovery of life saving solid organs. In particular, in the case procuring a facial allograft where there is prolonged recovery time. Here we report the outcome of the solid organs recovered from a deceased face allograft donor. Methods: W conducted a face allograft recovery from a heart beating deceased donor. The donor had succumbed to his injuries and was declared brain dead. The solid organs [heart, Lung, Liver, kidney and kidney/pancreas were allocated to five recipients]. The donor family agreed to donate the face to a wait listed recipient. It was determined that the procurement of the face would ideally be performed in the same hospital as the face transplant procedure. With careful planning the deceased donor was transported to the face recipient’s hospital. Careful coordination with the five solid organ recipient teams was needed. The face procurement lasted 24 hours. The thoracic and abdominal organs were procured in the standard fashion. Results: In the month following the procurement the organ procurement organization organized a conference call to learn the outcome of the placed organs. All were successfully placed and transplanted. One year from this organ procurement all organ recipients and the face transplant recipient are reported to be doing well with functioning grafts. Conclusions: With careful planning and coordination, a deceased donor can be relocated and solid organ recovery can proceed in the usual fashion. Organs recovered from our donor had excellent intermediate function.

What's Missing in Our Thinking About Quality of Life in VCA?

Drawing on the principles of respect for autonomy and beneficence, many scholars have argued that despite significant drawbacks of immunosuppression and surgery, vascularized composite allotransplantation (VCA), such as hand and face transplantation, has the potential to enhance the lives of patients who meet appropriate criteria and are well supported. This article provides a brief overview of the literature on VCA with a focus on hand transplantation (HTx) and offers a critique of the lack of empirical data on HTx patients' perspectives.