SYSTEMATIC REVIEW article

Front. Surg., 30 January 2026

Sec. Reconstructive and Plastic Surgery

Volume 13 - 2026 | https://doi.org/10.3389/fsurg.2026.1738957

Rewiring faces: advances and outcomes in facial nerve reconstruction after facial vascularized composite allotransplantation

  • 1. Department of Oral and Maxillofacial Surgery, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

  • 2. Division of Plastic and Reconstructive Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States

  • 3. Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany

  • 4. Department of Plastic, Hand, and Reconstructive Surgery, University Hospital Regensburg, Regensburg, Germany

  • 5. Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Hospital Ludwigshafen, Department of Plastic and Hand Surgery, University of Heidelberg, Ludwigshafen, Germany

  • 6. Vascularized Composite Allotransplantation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

  • 7. Innovative Therapies in Haemostasis, INSERM UMR-S 1140, University of Paris, Paris, France

Abstract

Background:

Facial vascularized composite allotransplantation (FVCA) provides transformative restoration for patients with severe craniofacial defects, but successful outcomes depend heavily on facial nerve (FN) reconstruction and reinnervation. Unlike standard nerve repair, FN coaptation in FVCA must address donor–recipient mismatch and immunologic variability. This systematic review synthesizes clinical and preclinical evidence on FN reconstruction strategies in FVCA and their functional outcomes.

Methods:

This review adhered to PRISMA 2020 guidelines and was registered with PROSPERO (ID: CRD420251029430). A comprehensive search of PubMed, EMBASE, Cochrane Library, Web of Science, and Google Scholar. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) and SYRCLE tool for preclinical studies.

Results:

Overall, n = 45 (11%) studies [n = 41 (91%) human, n = 4 (9%) preclinical] published between 2006 and 2025 were included. Human studies were predominantly case reports n = 18 (44%), case series n = 11 (27%), and cadaveric investigations n = 9 (22%). Across n = 139 (100%) documented nerve repair interventions (NRIs), direct coaptation was performed in n = 20 (14%), most commonly at the FN trunk or its buccal, zygomatic, marginal mandibular, and frontal branches n = 28 (20%). Nerve grafting was more frequent, in n = 62 (45%), typically using great auricular or thoracodorsal donor nerves; only n = 2 (1.4%) NRIs employed dual-level trunk and branch coaptation. Synkinesis was reported in n = 11 (7.9%) NRIs, and patient-reported outcomes, though inconsistently collected, indicated improvements in oral continence, speech, social integration, and psychosocial well-being. Secondary revisions occurred in n = 27 (19%) and infectious complications in n = 12 (8.6%) NRIs. Preclinical rodent and porcine models corroborated clinical evidence that combined motor and sensory nerve repair enhances functional recovery.

Conclusion:

FN reconstruction in FVCA is feasible and often results in partial functional recovery. However, outcomes remain heterogeneous and are influenced by surgical approach, immunologic status, and rehabilitative support. Standardized assessment tools should be more widely adopted to improve comparability and guide individualized treatment planning. Translational research and multicenter data collection are needed. FN reconstruction represents both a clinical challenge and an opportunity to improve long-term quality of life in FVCA recipients.

Systematic Review Registration: identifier CRD420251029430.

Graphical Abstract

1 Introduction

Facial vascularized composite allografts (FVCA), encompassing both full and partial facial transplants, represents an advanced reconstructive technique for selected patients (). Central to the success of this complex surgery is the intricate reconstruction of the facial nerve (FN), which is essential for reanimating facial musculature and restoring expressions ().

The FNs complex anatomy and critical role in facial movements present unique challenges in the context of transplantation, necessitating a thorough understanding of both microsurgical techniques and neurophysiological principles. Historically, various strategies have been employed to address FN injuries, ranging from direct nerve repair to the use of nerve grafts and conduits (). Recent advancements have introduced innovative techniques such as cross-FN grafts and the use of motor nerve transfers ().

In the context of facial transplantation, these approaches must be tailored to each patient's unique presentation, such as the specific pattern of nerve involvement, extent of injury (unilateral or bilateral), and individual anatomical or functional considerations, which can make achieving optimal outcomes more challenging (). Factors such as the initial trauma, the timing of FN repair, the distance of FN regeneration, the type of FN coaptation, and the potential for synkinesis or aberrant reinnervation might further complicate the recovery process (). Moreover, the immunological aspects of facial transplantation (high risk of acute rejection, immunogenic skin/mucosa tissue, immunosuppressants) may influence FN regeneration and functional outcomes, adding another layer of complexity to patient management (, ).

Given the critical importance of FN reconstruction for the success of facial transplantation, a comprehensive review of current techniques, outcomes, and emerging strategies is warranted. To date, there is a paucity of research synthesizing the current evidence of FN reconstruction in FVCA cases. Therefore, this review aims to consolidate existing literature on FN reconstruction within the context of FVCA, identify knowledge gaps, and provide insights that may guide future research and clinical practice. Because full functional restoration relies on both motor and sensory reinnervation, this review also includes sensory nerve interventions when they form an integral component of the reconstructive strategy.

2 Methods

This systematic review followed the PRISMA 2020 guidelines. Due to anticipated variability in study methodologies and reported outcomes, a narrative synthesis was employed in place of a meta-analysis. The complete review protocol was a priori registered with PROSPERO (ID: CRD420251029430).

2.1 Systematic search and data synthesis

A thorough literature search was conducted across PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, and Google Scholar (first 25 pages) to identify all relevant studies published up to July 30th, 2025. Because Google Scholar prioritizes highly cited and field-relevant studies in early pages, screening was limited to the first 25 pages, beyond which studies relevant to this specific research question rarely appear (, ). The search strategy focused on two primary concepts: i) “facial vascularized composite allotransplantation” and ii) “facial nerve reconstruction,” incorporating a range of related synonyms and MeSH terms. These two domains were combined using the Boolean operator “AND.” Complete search strings for each database are available in Supplementary Digital Content 1. Additionally, reference lists of all included articles were reviewed to identify any further eligible studies. Studies were included if they presented original, peer-reviewed data investigating facial vascularized composite allotransplantation with a focus on FN reconstruction. All study types, clinical, animal, cadaveric, or in vitro, were eligible, provided they directly addressed this topic. Sensory nerve interventions were also included when they formed an integral component of the reconstructive procedure, as comprehensive facial nerve repair encompasses both motor and sensory reinnervation. Articles had to be available in full text and published in English. Studies were excluded if they were not peer-reviewed, did not contain original data (e.g., systematic reviews or meta-analyses), or were unrelated to FVCA or nerve reconstruction. Titles and abstracts were independently screened by three reviewers (T.N., R.M., S.J.), after which full texts were assessed for eligibility. Any discrepancies were resolved in consultation with a senior reviewer (L.K.). The study selection process is illustrated in the PRISMA 2020 flow diagram shown in Figure 1.

Figure 1

To allow for comprehensive qualitative data synthesis, it was not feasible to categorize the data on a per-patient basis, since several publications in the literature describe different aspects of FN reconstruction following FVCA from the same patient and single patients underwent multiple nerve repair procedures. Furthermore, both clinical transplants and cadaveric studies are represented, with some undergoing multiple, sequential, or staged nerve repair procedures employing different techniques. To address this heterogeneity while still providing clinically relevant findings, each distinct clinical human nerve coaptation event is referred to herein as a “nerve repair intervention (NRI).” This classification encompasses any operative method performed in a clinical setting and allows for a granular analysis of surgical techniques without reducing complex, multi-nerve reconstructions into single “case” summaries. Cadaveric and preclinical coaptations were excluded from this specific metric and are discussed separately in the narrative synthesis. Consequently, for biodemographic variables such as age, only ranges rather than means were reported to minimize skewing. In line with this framework, each of the 139 identified clinical NRIs was treated as an independent event in descriptive summaries of surgical technique and outcome, ensuring a consistent representation of clinical reconstructive strategies.

2.2 Quality assessment

The quality of included studies was evaluated using appropriate tools depending on study type. Clinical studies were assessed using the Newcastle-Ottawa Scale (NOS), which rates studies across three domains: cohort selection, group comparability, and outcome assessment, with a maximum of nine stars indicating highest quality (). The NOS is most commonly applied to observational research, including cohort and case-control studies, making it suitable for the predominantly descriptive clinical designs included in this review. Preclinical studies were evaluated using the SYRCLE Risk of Bias tool (), which adapts the Cochrane framework for animal research and assesses factors such as allocation bias, blinding, and outcome reporting. The tool encompasses ten specific domains, including sequence generation, baseline characteristics, random housing, blinding of caregivers and outcome assessors, incomplete outcome data, and selective reporting, to provide a structured evaluation of internal validity. To determine levels of evidence, the Oxford Centre for Evidence-Based Medicine (OCEBM) framework was applied, ranking randomized trials and systematic reviews as Level I, and grading preclinical studies based on their translational potential (30). Detailed quality appraisal results are provided in Supplementary Digital Content 2, 3, and 4.

2.3 Data extraction

Data extraction was performed using a blinded dual-review process. The following parameters were collected from each study: Digital Object Identifier, study title, first author, study species (human or animal), year of publication, study type, sample size, recipient age at transplant, recipient sex, donor age, donor sex, follow-up duration, cause of injury, type of FVCA, donor nerve type, recipient nerve type, type of nerve graft, coaptation sites, suture type, use of intraoperative neuromonitoring, immunosuppression regimen, episodes of graft rejection including number and treatment, functional recovery (e.g., based on House-Brackmann (HB) Grading System (31), evidence of spontaneous facial movement recovery, time to first facial movement, electromyography (EMG) and nerve conduction study findings, facial symmetry at rest, during smiling, and brow elevation, development and severity of synkinesis, patient-reported outcomes including functional and quality-of-life measures, need for revision surgery including type and reason, occurrence of infections or other complications including treatment required, corticosteroid-related issues such as osteonecrosis, hyperglycemia, or weight gain, requirement for additional facial reanimation procedures such as cross-FN grafts or free muscle transfer, and a one-sentence summary of study findings.

3 Results

Across all screened studies (n = 402, 100%), a total of n = 41 (11%) human studies and n = 4 (0.9%) preclinical models met the a priori determined inclusion and exclusion criteria. The year of publication ranged from 2006 to 2025. Study types were predominantly case reports (n = 18, 44%) and case series (n = 11, 27%). Furthermore, n = 9 (22%) studies included human cadavers. The mean (SD) NOS-score was 5.0 (0.0), indicating overall low to moderate methodological quality.

3.1 Study demographics

Recipient age ranged from 19 to 64 years. Donor age ranged from 18 to 99 years. A total of n = 139 (100%) NRIs were reported. The majority of NRIs were performed in males (n = 71, 51%), and n = 29 (21%) in females. Follow-up durations ranged from 2 months to over 6 years.

Reported causes of facial injury necessitating FVCA and NRI encompassed ballistic trauma, burns, animal attacks, Neurofibromatosis type 1, and oncologic resections. The extend of FVCA ranged from partial face grafts involving perioral, nasal, or zygomatic units to full-face transplants, including osteomyocutaneous components. Full study demographics are available in Table 1.

Table 1

DOIStudy titleFirst authorYear of publicationStudy typeSample sizeRecipient ageRecipient sexDonor ageDonor sexFollow-up timeCause of InjuryType of facial VCA
DOI: 10.1016/S0140-6736 (06)68935-6First human face allograft: early reportDevauchelle et al.2006Case report138f46f4 monthsAnimal AttackCentral and lower face (nose, lips, chin, adjacent cheeks)
DOI: 10.1097/01.sap.0000227486.28556.3eTechnical and Anatomical Considerations of Face Harvest in Face TransplantationBaccarani et al.2006Cadaveric study2N/AN/AN/AN/AN/AN/AN/A
DOI: 10.1056/NEJMoa072828Outcomes 18 months after the first human partial face transplantation.Dubernard et al.2007Case report138f46f18 monthsDog biteN/A
DOI: 10.1016/j.bjps.2007.12.014Osteocutaneous face transplantationFollmar et al.2007Cadaveric study1N/AN/AN/AN/AN/AN/AMyocutaneous
DOI: 10.1007/s00104-007-1446-xFacial allograft transplantation: Fiction or reality? Sques in a fresh human cadaver modelMeßmer et al.2008Cadaveric study4N/AN/ARange: 50–90fN/AN/AType 1: Skin flap (sub-SMAS technique); Type 2: Osteocutaneous flap (Le Fort III segment)
DOI: 10.1016/S0140-6736 (08)61276-3Human facial allotransplantation: a 2-year follow-up studyGuo et al.2008Case report130m25m2 yearsAnimal AttackPartial face (nose, upper lip, parotid gland, front wall of maxillary sinus, infraorbital wall, zygomatic bone)
DOI: 10.1097/PRS.0b013e3181882146Face Transplant Graft Procurement: A Preclinical and Clinical StudyMeningaud et al.2008Cadaveric study and case report129mN/AmN/ANFMyocutaneous
DOI: 10.1097/PRS.0b013e3181954e8cMini-temporalis transfer as an adjunct procedure for smile restorationTerzis et al.2009Cohort study31N/AN/AN/AN/AMore than 3 monthsTraumaN/A
DOI: 10.1016/S0140-6736 (09)61155-7Near-total human face transplantation for a severely disfigured patient in the USASiemionow et al.2009Case report145fN/AfMore than 5 monthsBallistic traumaOsteomyocutaneous
DOI: 10.1001/archfacial.2009.80The Technical and Anatomical Aspects of the World's First Near-Total Human Face and Maxilla TransplantAlam et al.2009Case report145fN/AfN/AN/AN/A
DOI: 10.1097/prs.0b013e3181c2a5ccFacial Transplantation: An Anatomic and Surgical Analysis of the Periorbital Functional UnitVasilic et al.2010Cadaveric study12N/AN/ARange: 49–998 m, 4fN/AN/APeriorbital functional unit (eyelids)
DOI: 10.1097/PRS.0b013e318230c77bAn Update on Facial Transplantation Cases Performed between 2005 and 2010Siemionow et al.2010Case series13Range: 28–5911 m, 2 fRange: 25–6511 m, 2fN/AAnimal attack, neurofibromatosis, ballistic/explosion trauma, burn/electrical injury, cancerMyocutaneous and osteomyocutaneous VCA
DOI: 10.1016/j.transproceed.2011.06.030Reconstruction of a severe facial defect by allotransplantation in neurofibromatosis type 1: A case reportSicilia-Castro et al.2011Case report135m18m6 monthsNeurofibromatosis type 1Lower two-thirds of the face (osteomyocutaneous allograft), including chin osseous segment, skin, subcutaneous tissue, lips, perioral muscles, parotid glands, facial nerves
DOI: 10.1097/SLA.0b013e318226a607Full Face Transplant The First Case ReportBarret et al.2011Case report130m41mMore than 4 monthsBallistic traumaOsteomyocutaneous VCA
DOI: 10.1111/j.1600-6143.2010.03406.xFeasibility, Reproducibility, Risks and Benefits of Face Transplantation: A Prospective Study of OutcomesLantieria et al.2011Case series5Range: 27–39mN/AmRange: 7–38 monthsBallistic trauma, burn injury, neurofibromatosisOsteomyocutaneous and myocutaneous VCA
DOI: 10.1111/j.1600-6143.2010.03368.xRestoration of Facial Form and Function After Severe Disfigurement from Burn Injury by a Composite Facial AllograftPomohac et al.2011Case report159m60m15 monthsElectrical burnOsteomyocutaneous
DOI: 10.1097/PRS.0b013e31825dc25cNovel surgical technique for full face transplantationPomahac et al.2012Case series3N/AN/AN/AN/AN/ASevere facial defectsFull face allotransplantation (including scalp, eyelids, nose, maxilla, muscles, nerves, and vessels)
DOI: 10.1097/prs.0b013e31828bd394Nerve transfers for facial transplantation: a cadaveric study for motor and sensory restoration.Audolfsson et al.2013Cadaveric study15N/AN/AMean: 68.2, range: 49–9210 m, 5fN/AN/ASimulated face transplantation (midface, upper/lower lip, buccal region)
DOI: 10.1177/000348941312201106Long-term outcomes of facial nerve function in irradiated and nonirradiated nerve graftsLeong et al.2013Cohort study42Mean: 53.2, range: 16–8024 m, 18 fN/AN/A2 yearsFacial fractures, neuromaN/A
DOI: 10.1097/PRS.0b013e31828bd394Facial allotransplantation procurement using a transparotid approach: A new anatomical modelHorta et al.2014Cadaveric study3N/AN/AN/AN/AN/AN/AFull face allotransplant (including fronto-temporo-parietal scalp, eyelids, nose, muscles, lips, nerves, vessels)
DOI: 10.1002/micr.22216A functional periorbital subunit allograft: Vascular, anatomic, and technical considerations for future subunit facial transplantationMathes et al.2014Cadaveric study12N/AN/AN/AN/AN/AN/APeriorbital subunit (eyelids, medial/lateral canthal areas, inferior/superior periorbital skin)
DOI: 10.1016/j.bjps.2014.05.046Eyelid Transplantation: Lessons from a Total Face Transplant and the Importance of BlinkSosin et al.2015Case report137mN/AN/A1,1 yearsTrauma (avulsive ballistic injury)Total face, double-jaw, tongue
DOI: 10.1097/prs.0000000000000798Long-Term Multifunctional Outcome and Risks of Face Vascularized Composite AllotransplantationRoche et al.2015Case report155mN/AN/A3 yearsBallistic injuryN/A
DOI: 10.1097/SCS.0000000000002110Referred facial sensation on the hand after full face transplantationUysal et al.2016Case report119m37N/AN/ABurn injuryFull face transplant (excluding eyelids)
DOI: 10.1212/WNL.0000000000002409Surgical Optimization of Motor Recovery in Face TransplantationAycart et al.2016Case series2P1: 25, P2:57P1:m, P2:wN/AN/A3,5 yearsP1: electrical burn; P2: animal attackFull face allotransplantation
DOI: 10.1097/SCS.0000000000002305The First Immediate Face Transplant in the WorldMaciejewski et al.2016Case report131m30m2 yearsTraumatic injuryOsteomyocutaneous
DOI: 10.1097/SLA.0000000000001597Facial nerve regeneration after facial allotransplantation: A longitudinal clinical and electromyographic follow-up of lip movements during speechDe et al.2017Case report154m--3 yearsBallistic traumaLower two-thirds of face, maxillae, nasal bones, mandible, hard palate
DOI: 10.1016/j.bjps.2017.02.025The Effects of Lip-Closure Exercise on Lip Strength and Function Following Full Facial Transplantation: A Case ReportBridget et al.2017Case report140fN/AN/A1 yearBurn injuryOsteomyocutaneous VCA
DOI: 10.1044/2017_AJSLP-16-0101Assessment of Emotional Expressions after Full-Face TransplantationTopçu et al.2017Case series3P1:28, P2:37, P3:22mN/AN/AUp to 2 yearsBurn injuryOsteomyocutaneous VCA
DOI: 10.1155/2017/8789724Recovery of facial expressions using functional electrical stimulation after full-face transplantation.Topçu et al.2018Case series2N/AN/AN/AN/AN/AN/ATotal face VCA
DOI: 10.1186/s12984-018-0356-0Image-based Analysis of Emotional Facial Expressions in Full Face TransplantsBedeloglu et al.2018Case series2P1:22, P2:39mN/AN/AUp to 4 yearsN/ATotal face VCA (with and without eyelids)
DOI: 10.1007/s10916-018-0895-8Software-based video analysis of functional outcomes of face transplantationFischer et al.2018Case series7N/AN/AN/AN/A1 yearBurn injury, ballistic trauma, acid attackFace VCA
DOI: 10.1002/micr.30360The Helsinki approach to face transplantationLindford et al.2019Case series2P1:35, P2:58mN/AN/A30,5 monthsN/AOsteomyocutaneous VCA
DOI: 10.1016/j.bjps.2018.08.030Recognizing Emotional Expression as an Outcome Measure After Face Transplant.Dorante et al.2020Case series642N/AN/AN/A2N/AFace VCA
DOI: 10.1001/jamanetworkopen.2019.19247Full facial retransplantation in a female patient—Technical, immunologic, and clinical considerationsKauke et al.2021Case report152 (age at retransplantation), first transplant at age 45fSecond donor: 36, first donor: 56f0,5 yearsLye burnFull-face re-/transplant
DOI: 10.1111/ajt.16696Neuromotor Speech Recovery Across Different Behavioral Speech Modifications in Individuals Following Facial TransplantationEshghi et al.2021Cohort study7Range: 28–615 m, 2fN/AN/AEarly group: 2 months, late group: 42 monthsTrauma, burn injury, cancerFull or partial facial allografts (including lips, facial muscles, ± osteomyocutaneous components)
DOI: 10.3389/fneur.2020.593153Face Transplant: Current Update and First Canadian ExperienceGovshievich et al.2021Case report164m18 monthsBallistic traumaLe Fort III and bilateral sagittal split osteotomies in addition to skin
DOI: 10.1097/PRS.0000000000007890Facial Nerve Revascularization Strategies in Facial RestorationKhajuria et al.2022Case series541N/AN/AN/A6 yearsN/AFace VCA
DOI: 10.1097/GOX.0000000000004038Re-cognizing the new self: The neurocognitive plasticity of self-processing following facial transplantationAzevedo et al.2022Case report125mN/AN/A2 yearsBallistic traumaOsteomyocutaneous
DOI: 10.1073/pnas.2211966120Facial Expression after Face Transplant: An International Face Transplant Cohort ComparisonDorante et al.2023Cohort study13Mean: 40 ± 1411 m, 2fMean: 40 ± 13N/AMean: 3.6 ± 2.2Burn injury, ballistic traumaFull and partial face VCA, including midface, lower two-thirds, scalp and nasal structures
DOI: 10.1097/PRS.0000000000010242Anatomical study of trigeminal-facial nerve communications: Application to facial transplant surgeryIwai et al.2025Cadaveric study6N/AN/AMean: 76,53 m, 3fN/AN/AFace VCA

Patient demographics.

DOI, digital object identifier; VCA, vascularized composite allotransplantation; N/A, not available/not applicable; m, male; f, female; PX, patient X; SMAS, superficial musculoaponeurotic system; Le Fort III, anatomical classification of midface fracture used for orientation in facial surgery.

3.2 Facial nerve repair approaches

Reconstruction of the FN was a central component of NRI in all reported FVCA procedures. In n = 20 (14%) NRIs, direct coaptation of the donor FN branches to recipient FN stumps was performed. The most common coaptation sites (20%, n = 28) involved the main FN trunk and its distal branches—primarily the buccal, zygomatic, marginal mandibular, and frontal branches. Bilateral coaptation was reported in n = 6 (4.3%) NRIs, while n = 2 (1.4%) involved selective unilateral repair.

Nerve grafting was more common than direct coaptation, occurring in n = 62 (45%) of NRIs. Both autologous and allogenic grafts, most frequently the great auricular and thoracodorsal nerves, were used to bridge motor nerve gaps, particularly in complex or revision surgeries. While detailed outcome comparisons are limited, early data suggest that functional recovery (e.g., facial movement and symmetry) was achievable in both grafted and non-grafted NRIs, with no consistent evidence of inferior outcomes associated with graft use. Notably, in n = 2 (1.4%) NRIs dual-level coaptation at both the proximal trunk and distal branches of the FN was reported, reflecting a more aggressive reconstructive strategy aimed at optimizing reinnervation. However, whether this approach offered superior motor recovery remains unclear due to the absence of comparative or longitudinal outcomes.

Microsurgical suture techniques most commonly involved 8–0 to 10–0 nylon sutures, used in 32% (n = 45) NRIs, while alternative methods included fibrin-based adhesives such as fibrin sealant (n = 1,.07%) and Tisseel® (i.e., a commercially available fibrin glue used to promote hemostasis and tissue adhesion in microsurgery) in n = 5 (3.5%) NRIs. However, there is currently not enough comparative evidence within the reviewed NRIs indicating that the use of Tisseel® led to different functional outcomes compared to standard nylon sutures. In selected NRIs (n = 3, 2.2%), intraoperative neuromonitoring was used. Overall, FN repair was consistently prioritized in surgical planning, underscoring its critical role in achieving motor reanimation and facial symmetry. Further information is provided in Table 2.

Table 2

Study titleFirst authorYear of publicationStudy typeDonor nerveRecipient nerveType of nerve graftCoaptation sitesSuture typeIntraoperative neuromonitoring used?Immunosuppressive regimenGraft rejection episodesFunctional and sensory recoverySpontaneous facial movement recoveryTime to first movementEMG/NCS findingsFacial symmetrySynkinesis developmentPatient reported outcomes
Technical and Anatomical Considerations of Face Harvest in Face TransplantationBaccaraniet al.2006Cadaveric studyFN, mental, orbitalFN, mental, orbitalN/A (theorized coaptation only)N/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Osteocutaneous face transplantationFollmar et al.2007Cadaveric studyFN, trigeminal, greater auricular, supraorbital, infraorbital and mental nervesFN, trigeminal, greater auricular, supraorbital, infraorbital and mental nervesN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Facial allograft transplantation: Fiction or reality?: Sques in a fresh human cadaver modelMeßmer et al.2008Cadaveric studyType 1: Trigeminal nerve (sensory); Type 2: FN (motor)N/AN/AType 1: Trigeminal nerve branches (sensory); Type 2: FN (motor)N/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Facial Transplantation: An Anatomic and Surgical Analysis of the Periorbital Functional UnitVasilic et al.2010Cadaveric studyFN (temporal, zygomatic, buccal branches)N/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Nerve transfers for facial transplantation: a cadaveric study for motor and sensory restoration.Audolfsson et al.2013Cadaveric studySensory: Cervical plexus branches (greater auricular, supraclavicular, transverse cervical, lesser occipital nerves) Motor: Masseter nerveSensory: Mental nerve, infraorbital nerve; Motor: Buccal branches of FNDirect coaptation (nerve transfer; no graft used)Cervical plexus branches → mental nerve. Masseter nerve → buccal branches of the FN. Supraorbital nerve → infraorbital nerve (simulated)N/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Facial allotransplantation procurement using a transparotid approach: A new anatomical modelHorta et al.2014Cadaveric studyFN (main trunk, temporofacial/cervicofacial divisions & individual branches)N/ANone (technique avoids nerve grafts)Not specified (theoretical coaptation at temporofacial/cervicofacial divisions or distal branches)N/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
A functional periorbital subunit allograft: Vascular, anatomic, and technical considerations for future subunit facial transplantationMathes et al.2014Cadaveric studyMotor: Zygomatic and buccal branches of the FN; Sensory: Infraorbital, supraorbital, and supratrochlear nervesN/AN/AFN branches (zygomatic, buccalN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Anatomical study of trigeminal-facial nerve communications: Application to facial transplant surgeryIwai et al.2025Cadaveric studyTrigeminal nerve branches [ophthalmic (V1), maxillary (V2), mandibular (V3)] and facial nerve (FN) branchesN/AN/AV3 (mandibular nerve): Auriculotemporal (6/6 cases) and buccal (6/6 cases) nerves communicated with FN Mental nerve communicated in 3/6 cases; V2 (maxillary nerve): Infraorbital nerve communicated with FN in 3/6 cases; V1 (ophthalmic nerve): No communication with FNN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Face Transplant Graft Procurement: A Preclinical and Clinical StudyMeningaud et al.2008Cadaveric study and case reportFN & trigeminalFN & trigeminalDirect coaptationTrunkN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
First human face allograft: early reportDevauchelle et al.2006Case reportFN branches (zygomatic, buccal, mandibular), infraorbital, mental nervesFN stump (mandibular branch on left), infraorbital, and mental nervesNone (direct coaptation)Left mandibular branch of FN, b/l infraorbital and mental nerves10/0 Prolene (arteries), 9/0 Prolene (veins/nerves)N/AATG, TAC, MMF, PDN; donor bone marrow infusions1 episode at day 20; grade IN/AII rejection; treated with steroidsNot found (sensation recovery at 14 weeks; partial motor recovery at 12 weeks)Partial (upper lip movement at 12 weeks; incomplete smile)3 months (12 weeks)Not specified (sensation assessed via Semmes-Weinstein testing)Slight lower lip sagging; otherwise, good integrationN/APositive psychological acceptance; return to social life
Outcomes 18 months after the first human partial face transplantation.Dubernard et al.2007Case reportN/AN/AN/AN/AN/AN/AIntravenous ATG (TMG, Genzyme) for 10 days, oral TAC (target trough levels, 10 to 15 ng per milliliter throughout the first month), MMF (2 g per day), PDN (250 mg on day 1, 100 mg on day 2, and 60 mg per day through day 12, followed by a gradual taper)Extracorporeal photochemotherapy was introduced at 10 months to prevent recurrence of rejectionN/AN/AN/AN/AN/AN/AN/A
Human facial allotransplantation: a 2-year follow-up studyGuo et al.2008Case reportFN branches (details not fully specified)FN Stump (right buccal branches; anastomosis attempted)Direct coaptation (no nerve grafts used)FN anastomosis (exact branches unspecified)N/AN/ATAC, MMF, STR, humanized IL-2 receptor MAB3 episodes at 3, 5, 17 months; treated with TAC dose adjustment/steroid pulsesPartial motor recovery (incomplete smile), sensory recovery at 3 months (Semmes-Weinstein testing)Partial (upper lip movement; incomplete smile)N/AN/ASlight lower lip sagging; improved appearance post-revisionN/APositive psychological acceptance; reintegration into society
Near-total human face transplantation for a severely disfigured patient in the USASiemionow et al.2009Case reportFN, vagus, hypoglossalFN, vagus, hypoglossalB/l FN connected with standard epineural repair, donor vagus nerve used for interpositional graft & attached with 2 upper division trunks of right FN; left hypoglossal interpositional graft attached to upper division trunk of recipient FN. Both grafts were connected to main trunk of donor nerveDonor (main trunk), recipient (upper division of FN)N/AN/AInduction: Rabbit ATG, MPDN; Maintenance: TAC, MMF, low dose PDNDay 47-Graft mucosa (Tx with steroid bolus)Slow but progressing, as shown by improved facial mimetics with symmetric smiling and upper lip occlusion, upper lip and lower eyelid movements were imperfectN/AN/AN/AN/AN/A5 months PO, rates self-appearance 8/10, optimistic about rebuilding social life
The Technical and Anatomical Aspects of the World's First Near-Total Human Face and Maxilla TransplantAlam et al.2009Case reportN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Reconstruction of a severe facial defect by allotransplantation in neurofibromatosis type 1: A case reportSicilia-Castro et al.2011Case reportFN, infraorbital nerves, mental nerves (branches of trigeminal nerve)FN stumps (remaining after tumor resection), infraorbital & mental nervesAllograftFN, infraorbital & mental nerves (specific branches not detailed)Fibrin sealant used adjunctively, no further information was availableN/AInduction: Basiliximab (20 mg), TAC (6 mg), MPDN; Maintenance: PDN (10 mg/d), MMF (1.5 g/d), TAC (target 8–10 ng/mL).1, POD 28 (Banff grade III); TAC dose adjustment was taken into account, MPDN pulse therapy, topical TAC were usedQualitative descriptions only: motor recovery began at 6 months in levator labii and buccinator muscles; sensory recovery at 3–6 monthsYes6 months (levator labii and buccinator)Reinnervation evidence noted (electroneuromyographic examination confirmed motor recovery) Latency/amplitude changes were not quantifiedN/AN/AHigh satisfaction: improved speech, oral feeding, and social reintegration (no standardized scales like FACE-Q used)
Full Face Transplant The First Case ReportBarret et al.2011Case reportTrigeminal (supraorbital, infraorbital, mandibular nerves) & buccal, zygomatic, orbicularis oculi, frontal branches of FNTrigeminal (supraorbital, infraorbital, mandibular nerves) & buccal, zygomatic, orbicularis oculi, frontal branches of FNDirect coaptationN/A (end-to-end anastomosis)N/AN/AInduction: TMG, PDN; TAC, MMF (switched to sirolimus)Yes (2, from MMF switched to Sirolimus)At 4 months PO: regained active movement of the frontalis muscles, lateral portion of zygomatic muscles, upper orbicularis oculi muscles & unrestricted masticatory movements. Movement in some areas were still partial, pt was unable to close his eyes completelyN/AN/A (able to start soft diet 2 weeks PO)EMG 75 days PO: no signs reinnervation; 120 days initial signs of muscle activity detectedN/AN/AN/A (immediate PO reaction positive)
Restoration of Facial Form and Function After Severe Disfigurement from Burn Injury by a Composite Facial AllograftPomohacet al.2011Case reportFN, buccal, infraorbitalFN, buccal, infraorbitalNeurorrhaphyFN branches (5 on right side, 6 on left side), immediately anterior to parotid glandN/AN/AInduction: MPDN, Rabbit ATG, MMF; Maintenance: MMF & TACYes, at day 17 (Tx: steroids)Gradual improvement after 6 monthsYesN/A (by 1 yr PO pt could smile symmetrically & gained control of upper lip)N/A1 year PO pt had symmetric smileNoPt returned to living facility 5 weeks PO, fully integrated into community with enhanced social capacity, reconnected with divorced wife and daughter & prioritized function over aesthetic appearance
Eyelid Transplantation: Lessons from a Total Face Transplant and the Importance of BlinkSosin et al.2015Case reportFN branches: buccal, zygomatic; supraorbital, supratrochlear nerves preserved but not coaptedFN stump (middle branch required nerve grafting)nerve grafting used for middle branch due to insufficient lengthZygomatic, buccal, middle branch required nerve graftingN/AYes (nerve stimulation with checkpoint surgical, which is a nerve stimulator)Not specified (corticosteroids mentioned in discussion)N/A7.5 months (13.5 months after FT) after revision Sx to correct involuntary blink reflex; right eye (10–40%), left eye (60–90%); HB-scores not reported; voluntary blink preserved, involuntary blink improved post-transplant (70% right eye, 100% left eye) but temporarily impaired post-revisionYes (improved involuntary blink post-transplant)N/AN/AQualitative improvement notedN/APt reported comfort and artificial tear use noted
Long-Term Multifunctional Outcome and Risks of Face Vascularized Composite AllotransplantationRoche et al.2015Case reportN/AN/AN/AN/AN/AN/AMaintenance therapy consists of corticoids, TAC, MMF in minimal dosesRejection successfully treatedN/AYes1 monthYesN/AN/AN/A
Referred facial sensation on the hand after full face transplantationUysal et al.2016Case reportInfraorbital, supraorbital, mental, and frontal branches of the FNFN trunk (lower branches)Direct coaptation (no graft specified)B/l infraorbital, supraorbital, and mental nerves; Frontal branches coapted separately; Lower FN branches coapted to recipient's FN trunkN/AN/AInduction: ATG, PDN; Maintenance: TAC, MMF, PDNN/ANot explicitly reported; EMG at 6 months confirmed reinnervation in frontalis, orbicularis oculi and orbicularis oris musclesPartial recovery (e.g., eyebrow movement, lip pursing) but emotional expressions (smile, anger) remained incomplete at 2 yearsMotor activity detected by EMG at 6 months; functional movements observed gradually thereafterReinnervation in frontalis, orbicularis oculi and orbicularis oris muscles at 6 months but incomplete recovery of emotional facial expressions was notedAesthetic outcome implied by “adequate recovery of primary sensory modalities”N/AReferred facial sensations, touch on hands/fingers perceived as sensations on lips, forehead, and earlobes (topographically mapped), improved sensory modalities (pain, light touch) seen but incomplete two-point discrimination was observed
The First Immediate Face Transplant in the WorldMaciejewski et al.2016Case reportFN & branches (trunk left side, branches of right side); mental nerveFN & branches (trunk left side, branches of right side); mental nerveDirect coaptation of FN; autologous nerve forearm graft for b/l mental nervesDirect coaptation FN, autologous forearm nerve graft for mental nerves (donor mental nerves connected to recipient auricular magnus using grafts)N/AN/AInduction: ATG, TAC, MMF, MPDN; Maintenance: TAC, MMF, MPDNYes (POD 34, grade 2 histopathology, tx with steroids)N/A (b/l sensation recovery by 8 weeks PO)YesN/AN/AN/AN/AN/A
Facial nerve regeneration after facial allotransplantation: A longitudinal clinical and electromyographic follow-up of lip movements during speechDe Letter et al.2017Case reportNot explicitly reported (assumed FN)Not explicitly reported (assumed FN stump)N/AN/AN/AN/AN/AYes (1 episode at 4 months, tx with immunosuppressants)Not reported; EMG showed reinnervation starting at 1 month, clinical improvement over 38 monthsEMG activity detected at 1 month, gradual clinical improvement1 month (EMG activity); visible movement timing not specifiedEarly reinnervation at 1 month, increasing amplitude, decreasing reaction times over 38 monthsN/AN/AFacial Disability Index (FDI), Voice Handicap Index (VHI), Speech Handicap Index (SHI), Oral Health Impact Profile (OHIP-14) scores provided at multiple time points
The Effects of Lip-Closure Exercise on Lip Strength and Function Following Full Facial Transplantation: A Case ReportBridget al.2017Case reportN/AN/AAllograft5 FNsN/AN/AN/AN/ALip strengthening exerciseAbility to drink from a straw & communicate via facial expressionN/AN/AYesN/ABetter straw use, enhanced facial communication
Full facial retransplantation in a female patient—Technical, immunologic, and clinical considerationsKauke et al.2021Case reportFN branchesFN remnants (from prior transplantN/AFN coaptation was performed at the level of divisions, with coaptation of three FNs divisions on the left and four FN divisions on the right (7 coaptation sites)N/AN/AInduction: ATG, MMF, MPDN; Maintenance: PDN (10 mg QD), TAC (3 mg BID, goal 8–10 ng/mL), MMF (1,000 mg BID); Prophylaxis: Valganciclovir (CMV), trimethoprim-sulfamethoxazole (PCP)1st transplant: chronic antibody-mediated rejection (AMR) and recurrent T cell-mediated rejection (TCMR), leading to irreversible graft loss at 88 months. Retransplant: Grade III TCMR at 3 and 4 months post-retransplant, treated with STR and alemtuzumabNot reported (clinical improvement noted at 6 months post-retransplant)N/AN/AN/AN/AN/APsychosocial challenges noted (e.g., pain, functional limitations) but no quantitative scores (e.g., FDI, FACE-Q) were provided
Face Transplant: Current Update and First Canadian Experience.Govshievich et al.2021Case reportN/AMicrosurgical anastomoses of FN (3 branches) & infraorbital nerves were performed bilaterallyAllograftN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
Re-cognizing the new self: The neurocognitive plasticity of self-processing following facial transplantationAzevedo et al.2022Case reportN/AN/AN/AN/AN/AN/AN/AN/AN/AYesN/AEMG 2 years PO noted improvement, FN function & motor recruitment that correlated with improved speech & facial functionNot reported but based on included photos pt had excellent facial/smile symmetryN/APt returned to pre-injury daily activities
An Update on Facial Transplantation Cases Performed between 2005 and 2010Siemionow et al.2010Case seriesFN & its branches repaired in 8 pts, 4 pts had infraorbital nerve repairs, 2 pts had mental nerve repairs, 1 pt had buccal & supraorbital nerve repairAll direct coaptation of nerves done except for 1st pt in mental nerve repair; donor nerve stumps placed near mental foramen. Most underwent b/l FN repair, 1st pt had left mandibular branch repair but right FN was not well coaptedDirect coaptation (no graft specified)Not specified (theoretical coaptation at temporofacial/cervicofacial divisions or distal branches)N/AN/APt 1: Induction (ATG, MMF, PDN), Maintenance (TAC, sirolimus, MMF, PDN, IL-2R Ab); pt 2: Induction (TAC, MMF,MPDN, IL-2R Ab), Maintenance (TAC, MMF,PDN, IL-2R Ab); pt 3: Induction (Antilymphocyte serum, PDN), Maintenance (TAC, MMF, PDN); pt 4: Induction (Rabbit ATG, MPDN, TAC), Maintenance (TAC, MMF, PDN)N/AQualitative descriptions mentioned only for 4 pts: 1st pt (upper lip motion by 12 weeks, lower lip motion at 4 months, mouth closure by 6 months, smile at 14–18 months, chin & nose pyramidal muscle motion seen by 12 months); 2nd pt (no time frame reported, eat drink and speak normally, FN not fully functional); 3rd pt (at 6 months orbicularis oculi contraction, by 9 months spontaneous mimicry, by 10 days eat and speak, at 12 months facial motor function); 4th pt (no time frame-upper lip occlusion, facial mimicry, eat & drink from cup, speak clearly) qualitative descriptions only: motor recovery began at 6 months in levator labii and buccinator muscles; sensory recovery at 3–6 monthsN/AN/AN/AN/AN/AN/A
Feasibility, Reproducibility, Risks and Benefits of Face Transplantation: A Prospective Study of OutcomesLantieri et al.2011Case seriesB/l FN, trigeminalB/l FN, trigeminalN/AN/AAll nerve coaptations were glued with Tisseel R (a fibrin sealant)N/AInduction: ATG, TAC, MMF; Maintenance: TAC, MMF, PDN3 pts: 1 episodeData present of 3 pts (in 2 pts voluntary muscle contraction of zygomatic & orbicular oris; in 1 pt right zygomatic was absent, right orbicularis oris was absent along with absent complete mouth closureYesN/AEMG: By 6 months PO voluntary contraction of left orbicularis oculi was seen, in both orbicularis oris by 12 months motor & sensory innervarion b/l restored; 11 months PO no motor recovery was observed, at right side-correction of coaptation (appeared macroscopically normal IO)N/AN/AOverall improvement with SF-36, MCS & QOL testing
Novel surgical technique for full face transplantationPomahac et al.2012Case seriesFN branches (zygomatic, buccal), sensory nerves (supraorbital, infraorbital, mental)FN & its branches, hypoglossal nerve & sensory nerve stumps of supraorbital, infraorbital, mentalAllografts (without parotidgland)FN branches (zygomatic, buccal), sensory nerves (supraorbital, infraorbital, mental)N/ANoInduction immunosuppressionNoN/AYesN/AN/AImproved aesthetics reported (due to exclusion of parotid glands), but no scoring doneN/AN/A
Surgical Optimization of Motor Recovery in Face TransplantationAycart et al.2016Case seriesPt 1: FN divisions (superior/inferior) and thoracodorsal nerve (autograft). Pt 2: FN branches, masseter nerve (transfer), and great auricular nerve (graft)Pt 1: superior and inferior divisions of the left FN, right frontal, zygomatic, buccal and marginal mandibular branches were identified and isolated; P2: Six FN branches were identified b/l and on the right, all were directly coapted including the frontal, zygomatic, buccal, marginal and mandibular branchesAutografts: Thoracodorsal nerve (Pt 1), greater auricular nerve (Pt 2); Nerve transfer: Masseter nerve → buccal branches (Pt 2)FN branches (frontal, zygomatic, buccal, marginal mandibular) Masseter nerve → buccal branches (P2)8–0 nylon interrupted sutures (Pt 1); 7–0 nylon interrupted sutures (Pt 2)Yes (NIM-2.0 device during 2nd pt revision surgery)N/AN/AN/AYes (evidenced by regained control of facial muscles at 6–9 months)6 monthsPt 2: low-amplitude right facial compound muscle action potential at 11 months (indicating partial reinnervation)Improved over time (qualitative assessment via Sunnybrook scores and photographic analysis)Yes (graded as mild/moderate using Sunnybrook system); pt 1: synkinesis with forehead wrinkle and lip pucker; pt 2: synkinesis with smiling and lip puckeringHigh satisfaction mentioned (improved oral control, speech, and social reintegration) but no standardized scales (e.g., FACE-Q) were used
Assessment of Emotional Expressions after Full-Face TransplantationTopçu et al.2017Case seriesN/A B/l FN trunks were coapted to those of the donorN/AN/AN/AN/AN/AN/AN/AN/ABy the end of the 2nd year/8th monthN/AN/AN/AN/A
Recovery of facial expressions using functional electrical stimulation after full-face transplantation.Topçu et al.2018Case seriesN/AN/AN/AN/AN/A N/AFor all 3 pts, TMG (1.25 mg/kg), PDN (initiated at 1,000 mg/day and decreased PO) were administered IO; at 7 days PO, TAC (0.2 mg/kg, serum level 15–20 ng/mL) was initiated; TMG was discontinued after the 10th day Thereafter, treatment was continued with PDN (20 mg/day), TAC and MMF (2 g/day)N/AN/AN/AN/ASeen in 3rd ptN/AN/AN/A
Image-based Analysis of Emotional Facial Expressions in Full Face TransplantsBedeloglu et al.2018Case seriesN/AN/AN/AN/AN/AN/AN/ANoN/AN/AN/AN/AGabor lbp analysis (photographic)Yes, but not gradedN/A
Software-based video analysis of functional outcomes of face transplantationFischer et al.2018Case seriesN/AN/AN/AN/AN/AN/AN/AN/ANoYes, except eyebrow lift3 monthsNoYes, except eyebrow lift, emotient software (photographic)Yes, but not gradedN/A
The Helsinki approach to face transplantationLindford et al.2019Case seriesN/AN/AAllograftN/AN/AN/ATMG as induction & TAC, MMF as maintenanceNo, Banff consensus criteria was used as backupSunnybrook and Terzis scores assessed for 30 monthsN/AN/AN/AYes in 1st pt but partial, slight movement in 2nd ptN/AN/A
Recognizing Emotional Expression as an Outcome Measure After Face Transplant.Dorante et al.2020Case seriesN/AN/AN/AN/AN/AN/AN/AN/AN/AYes, except happiness24 monthsYesN/AN/AN/A
Facial Nerve Revascularization Strategies in Facial RestorationKhajuria et al.2022Case seriesN/AN/AAllograftN/AN/AN/ANoN/AN/AN/AN/AN/AN/AN/AN/A
Mini-temporalis transfer as an adjunct procedure for smile restorationTerzis et al.2009Cohort studyN/AN/AAllograftN/AN/AN/AN/AN/AYesYesN/AYes, for 25 ptsN/AN/AN/A
Long-term outcomes of facial nerve function in irradiated and nonirradiated nerve graftsLeong et al.2013Cohort studyGreater auricular, sural, hypoglossal, Ansa cervicalisFNN/AN/ASep 9–0N/AN/AN/A45% of patients had an HB grade of III or IV at long-term follow-up, the best outcome (HB grade III) was observed after cross-facial grafting with sural nerveN/AN/AN/AN/AN/AN/A
Neuromotor Speech Recovery Across Different Behavioral Speech Modifications in Individuals Following Facial TransplantationEshghi et al.2021Cohort studyFN branches (buccal, marginal mandibular, zygomatic, frontal)FN stump (coapted branches; exact details not specified)N/ABuccal, marginal mandibular, zygomatic, frontal branchesN/AN/AN/AN/ANot found (kinematic measures used: speed/range of lip/jaw movement)N/AN/ANot specified (motion capture used for biomechanical analysis)N/AN/AN/A
Facial Expression after Face Transplant: An International Face Transplant Cohort ComparisonDorante et al.2023Cohort studyFN branchesFN branches (trunk/branch level)Autograft, Allograft (donor nerve grafts)At distal branch & proximal trunk levelN/ANoN/AN/AHB-score: Median motor function recovery: 36.9%, Smile: 37.2%, varying by cohortN/AN/AN/AAssessed via FaceReader software—ISV comparison with controlsN/AFDI reported outcomes for Boston cohort with mean of 69.1%

Nerve reconstruction details.

FN, facial nerve; b/l, bilateral; pt, patient; pts, patients; ATG, antithymocyte globulin (immunosuppressive induction agent); TAC, tacrolimus (calcineurin inhibitor for maintenance immunosuppression); MMF, mycophenolate mofetil (antimetabolite for immunosuppression); PDN, prednisone (oral corticosteroid); MPDN, methylprednisolone (intravenous corticosteroid); TMG, thymoglobulin (rabbit-derived polyclonal antibody preparation for induction); STR, steroids (general corticosteroid use); IL-2R Ab, interleukin-2 receptor antibody (monoclonal immunosuppressive agent); CMV, cytomegalovirus; PCP, Pneumocystis jirovecii pneumonia; EMG, electromyography; NCS, nerve conduction studies; HB, House–Brackmann grading system for facial nerve function; QOL, quality of life; MCS, mental component score of the SF-36; PO, postoperative; POD, postoperative day; IO, intraoperative; ISV, intensity score value used in facial expression analysis; FACE-Q, validated patient-reported outcome instrument for facial aesthetics and functional recovery.

3.3 Functional outcomes following facial nerve coaptation

Functional motor recovery following FN reconstruction was variably reported, with significant heterogeneity in outcome measures, follow-up durations, and assessment modalities.

One assessment modality was the HB Grading System. Quantitatively, the median time to first EMG-confirmed activity was 4.1 months (range: 1–6 months), and the median onset of voluntary facial motion was 5.3 months (range: 3–9 months) in cases reporting sufficient detail (n = 12 NRIs, 8.6%). HB grade outcomes similarly showed measurable improvement in a subset of recipients (n = 42): 45% of the cases in this one study achieved HB grade III–IV, and where numerical data allowed, this corresponded to an estimated 95% CI of ∼30%–61% (n = 14 NRIs, 11%). Spontaneous facial movement was regained with initial voluntary motion at approximately 3–6 months. postoperatively, particularly in muscles such as the levator labii, orbicularis oris, and zygomaticus major.

EMG evidence of reinnervation was typically first reported between 1 and 6 months postoperatively, with gradual improvements in amplitude and reduced latency over time. In more detailed NRIs (n = 44, 32%), EMG confirmed motor unit recruitment in the frontalis, orbicularis oculi, and mentalis muscles, with recovery continuing for up to 38 months. Despite partial or delayed reinnervation in n = 3 (2.2%) NRIs, facial symmetry at rest and during movement (smile, brow elevation) generally improved over time and was often assessed qualitatively or through photographic software (e.g., FaceReader™, Emotient™, or Gabor LBP analysis).

Moreover, synkinesis was reported in n = 11 (7.9%) NRI recipients, typically graded as mild to moderate and involving unintended movements during smiling or lip pursing. Patient-reported outcomes, though inconsistently collected, generally reflected high satisfaction. Positive trends were observed in domains such as oral continence, speech, social reintegration, and psychosocial wellbeing. Scales like the Facial Disability Index (FDI; i.e., a reliability and validity of a disability assessment instrument for disorders of the facial neuromuscular system), Oral Health Impact Profile (OHIP-14; i.e., a 14-item short form assessing the social impact of oral disorders on quality of life), and Short Form-36 Health Survey (SF-36; i.e., a 36-item instrument measuring general health-related quality of life across eight domains) were selectively used to quantify functional gains, although qualitative assessments predominated. Overall, these findings highlighted that while recovery is gradual and incomplete after many NRIs, substantial improvements in motor function and quality of life are attainable with appropriate nerve reconstruction strategies. Complete functional outcomes are provided in Table 2.

3.4 General and facial nerve–related complications

Acute graft rejection episodes were reported in n = 12 (8.6%) NRIs, often occurring within the first 1–2 months postoperatively and managed with steroid boluses, tacrolimus adjustments, or extracorporeal photochemotherapy. Although functional motor recovery (e.g., HB grade III–IV) was achieved, several NRIs (n = 69, 50%) required further procedures, including nerve transfers, interposition grafts, or cross-FN grafting due to incomplete reinnervation, asymmetric contraction, or coaptation failure. Here, secondary surgeries were common (n = 27, 19% NRIs), including nerve re-coaptation, hematoma evacuation, and soft tissue adjustments to optimize smile symmetry and FN branch alignment. In n = 12 (8.6%) NRIs, infectious complications, including CMV, HSV, and Pseudomonas-related necrosis, led to graft deterioration or systemic morbidity. Corticosteroid-related adverse effects (e.g., hyperglycemia, myalgia, osteonecrosis) were reported in n = 3 (2.2%) NRI recipients. Conversely, FN-specific sequelae such as neuropraxia, synkinetic overactivation, and delayed reinnervation were linked to functional deficits in n = 18 (13%) NRIs.

Overall, these findings emphasized the delicate interplay between immunologic control and precise microsurgical FN repair in achieving optimal FN function post-transplant (Table 3).

Table 3

Study titleFirst authorYear of publicationFollow-up timeImmunosuppression RegimenGraft Rejection EpisodesSynkinesis DevelopmentNeed for Revision SurgeryInfection/ComplicationsCorticosteroid-Related IssuesNeed for Additional Facial Reanimation Procedures
First human face allograft: early reportDevauchelle et al.20060.33 (4 months)ATG, TAC, MMF, PDN; donor bone marrow infusions1 episode at day 20; grade I-II rejection; treated with steroidsN/AN/ACandida stomatitis (day 18); transient thrombocytosisN/AN/A
Technical and Anatomical Considerations of Face Harvest in Face TransplantationBaccarani et al.2006N/AN/AN/AN/AN/AN/AN/AN/A
Outcomes 18 months after the first human partial face transplantationDubernard et al.200718 monthsIntravenous ATG (Thymoglobulin, Genzyme) × 10 days, oral tacrolimus (trough 10–15 ng/mL, first month), mycophenolate mofetil 2 g/day, prednisone 250 mg day 1: 100 mg day 2: 60 mg/day to day 12, then taperedExtracorporeal photochemotherapy added at month 10 to prevent rejection recurrenceN/AN/AViral infectionN/AN/A
Osteocutaneous face transplantationFollmar et al.2007N/AN/AN/AN/AN/AN/AN/AN/A
Facial allograft transplantation: Fiction or reality?: Sques in a fresh human cadaver modelMeßmer et al.2008N/AN/AN/AN/AN/AN/AN/AN/A
Human facial allotransplantation: a 2-year follow-up studyGuo et al.20082 yearsTAC, MMF, STR, humanized IL-2 receptor MAB3 episodes at 3, 5, 17 months; treated with TAC dose adjustment/steroid pulsesN/AYes (two revisions: scar revision, autologous cartilage graft for orbital floor)Hyperglycemia (new-onset diabetes mellitus), transient thrombocytosis, dysbiosis of intestinal floraHyperglycemia (managed with insulin/medication)N/A
Face Transplant Graft Procurement: A Preclinical and Clinical StudyMeningaud et al.2008N/AN/AN/AN/AN/AN/AN/AN/A
Mini-temporalis transfer as an adjunct procedure for smile restorationTerzis et al.2009Longer than 3 monthsN/AN/AN/AN/AN/AN/ACross-facial grafting or mini-hypoglossal-to-facial nerve
Near-total human face transplantation for a severely disfigured patient in the USASiemionow et al.2009N/A (last mentioned 5 months)Induction: Rabbit ATG, MPDN; Maintenance: TAC, MMF. Low-dose PDNDay 47-graft mucosa (Tx steroid bolus)N/AN/ANoneN/AN/A
The Technical and Anatomical Aspects of the World's First Near-Total Human Face and Maxilla TransplantAlam et al.2009N/AN/AN/AN/AN/AN/AN/AN/A
Facial Transplantation: An Anatomic and Surgical Analysis of the Periorbital Functional UnitVasilic et al.2010N/AN/AN/AN/AN/AN/AN/AN/A
An Update on Facial Transplantation Cases Performed between 2005 and 2010Siemionow et al.2010N/APt 1: Induction—ATG, MMF, prednisolone; maintenance—tacrolimus, sirolimus, MMF, prednisolone, IL-2R Ab. Pt 2: Induction—tacrolimus, MMF, MPDN, IL-2R Ab; maintenance—tacrolimus, MMF, PDN, IL-2R Ab. Pt 3: Induction—antilymphocyte serum, PDN; maintenance—tacrolimus, MMF, PDN. Pt 4: Induction—rabbit ATG, MPDN, tacrolimus; maintenance—tacrolimus, MMF, PDNN/AN/AN/AN/AN/AN/A
Reconstruction of a severe facial defect by allotransplantation in neurofibromatosis type 1: A case reportSicilia-Castro et al.20116 monthsInduction: Basiliximab (20 mg), TAC (6 mg), MPDN. Maintenance: PDN (10 mg/d), MMF (1.5 g/d), TAC (target 8–10 ng/mL)1, POD 28 (Banff grade III); TAC dose adjustment, MPDN pulse therapy, topical TACN/AYes (surgical revision at day 7 for hematoma evacuation)Yes, IO: Significant blood loss (24 units packed RBCs, plasma/platelets), PO: Prerenal insufficiency (months 4–5; managed with TAC reduction).N/AN/A
Full Face Transplant The First Case ReportBarret et al.2011N/A [last mentioned 4 months (Discharge)]Induction: TMG, PDN; PDN, TAC, MMF (switched to sirolimus)Yes (2, MMF switched to Sirolimus)N/AVenous thrombosis left external jugular and left retromandibular veins-exploration and re-anastomosisVenous thrombosisNoneN/A
Feasibility, Reproducibility, Risks and Benefits of Face Transplantation: A Prospective Study of OutcomesLantieria et al.20110.58–3.2 years (7–38 months)Induction: ATG, TAC, MMF; Maintenance: TAC, MMF, PDN3 pts with 1 episode eachN/AYes (insufficient coaptation of right FN)All pts (mostly bacterial; CMV; HSV; 1pt with pseudomonas aeruginosa infection led to significant necrosis, anoxic cardiac arrest after surgery 2/2 tracheotomy obstruction led to severe anoxic brain injury and eventually death)N/A1 pt-absence of motor recovery on the right side after 11 months led re-intervention-zygomatic muscle contraction appeared 1st, complete mouth closure by 8–12 months
Restoration of Facial Form and Function After Severe Disfigurement from Burn Injury by a Composite Facial AllograftPomohac et al.20111,25 yearsInduction: MPDN, Rabbit ATG, MMF; Maintenance: MMF & TACYes, day 17 (Tx. steroids)NoYes (trimming of redundant cheek skin 6 months after FT)N/A (rosacea from donor Tx. topical metronidazole)N/AN/A
Novel surgical technique for full face transplantationPomahac et al.2012N/AInduction immunosuppressionNoN/ANoNoN/AN/A
Nerve transfers for facial transplantation: a cadaveric study for motor and sensory restorationAudolfsson et al.2013N/AN/AN/AN/AN/AN/AN/AN/A
Long-term outcomes of facial nerve function in irradiated and nonirradiated nerve graftsLeong et al.20132 yearsN/AN/AN/ANoNoNoCross-facial grafting with sural nerve in 9th pt, greater auricular nerve in 15 pt with cable nerve graft, 16th pt had transposition nerve repair, radiotherapy in 21st pt, gold weight, botox, fat injection
Facial allotransplantation procurement using a transparotid approach: A new anatomical modelHorta et al.2014N/AN/AN/AN/AN/AN/AN/AN/A
A functional periorbital subunit allograft: Vascular, anatomic, and technical considerations for future subunit facial transplantationMathes et al.2014N/AN/AN/AN/AN/AN/AN/AN/A
Eyelid Transplantation: Lessons from a Total Face Transplant and the Importance of BlinkSosin et al.20151,1 yearsNot specified (corticosteroids mentioned in discussion)N/AN/AYes (Le Fort III advancement, brow elevation at 6 months; b/l lower eyelid blepharoplasty at 9 months)Temporary neuropraxia, corneal exposure post-revision; tx: artificial tearsN/AN/A
Long-Term Multifunctional Outcome and Risks of Face Vascularized Composite AllotransplantationRoche et al.20153 yearsMaintenance therapy of corticoids, TAC, MMF in minimal dosesRejection successfully treatedN/AN/AMyalgia, aspergillomaN/AN/A
Referred facial sensation on the hand after full face transplantationUysal et al.20162 yearsInduction: ATG, PDN; Maintenance: TAC, MMF, PDNN/AN/AN/AIII-defined pain sensation on the face, incomplete recovery of emotional facial expressionsN/AN/A
Surgical Optimization of Motor Recovery in Face TransplantationAycart et al.20163,5 yearsN/AN/AYes (graded as mild/moderate using Sunnybrook system)Pt 2: Yes (nerve transfer at 11 months post-transplant due to impaired motor recovery)N/AN/AYes (Pt 2 required nerve transfer and interposition graft)
Pt 1: Synkinesis with forehead wrinkle and lip pucker
Pt 2: Synkinesis with smiling and lip puckering
The First Immediate Face Transplant in the WorldMaciejewski et al.2016N/A (2 yr documented)Induction: ATG, TAC, MMF, MPDN; Maintenance: TAC, MMF, MPDNYes [POD 34 (Grade 2 histopathology), Tx steroids]N/AN/AN/AN/AN/A
Facial nerve regeneration after facial allotransplantation: A longitudinal clinical and electromyographic follow-up of lip movements during speechDe Letter et al.20173 yearsN/AYes (1 episode at 4 months, treated with immunosuppressants)N/AN/AYes (Aspergillus infection at 12 months PO, treated)N/AN/A
The Effects of Lip-Closure Exercise on Lip Strength and Function Following Full Facial Transplantation: A Case ReportBridget et al.20171 yearN/AN/AN/AN/AN/AN/AYes, an 8-week targeted lip-strengthening biofeedback program was trialed with positive results
Assessment of Emotional Expressions after Full-Face TransplantationTopçu et al.20171–2 yearsN/AN/AN/AN/AN/AN/AN/A
Recovery of facial expressions using functional electrical stimulation after full-face transplantationTopçu et al2018N/AFor all 3 pts, TMG (1.25 mg/kg) and prednisolone (initiated at 1,000 mg/day and decreased PO) were administered during the surgery. At 7 days PO, TAC (0.2 mg/kg, serum level 15–20 ng/mL) was initiated. TMG was discontinued after the 10th day. Thereafter, treatment was continued with PDN (20 mg/day), TAC, and MMF (2 g/day)N/AN/AN/AN/AN/AN/A
Image-based Analysis of Emotional Facial Expressions in Full Face TransplantsBedeloglu M20183–4 yearsN/AN/AYes, but not gradedN/AN/AN/ARehabilitation still going on
Software-based video analysis of functional outcomes of face transplantationFischer et al.20181 yearN/AN/AYes, but not gradedN/AN/AN/AN/A
The Helsinki approach to face transplantationLindford et al.201930,5 monthsTMG as induction & TAC, MMF as maintenanceNo, Banff consensus criteria usedN/AYesNasopalatine fistula, EBV, CMV infection (in 1st pt) sialocele, oronasal fistula, palatine necrosis (in 2nd pt)DiabetesNo
Recognizing Emotional Expression as an Outcome Measure After Face TransplantDorante et al.20202 yearsN/AN/AN/AN/AN/AN/AYes
Full facial retransplantation in a female patient—Technical, immunologic, and clinical considerationsKauke et al.20210,5 years post re-transplantation (7 years 3 months total from first transplant)Induction: ATG, MMF, MPDN; Maintenance: PDN (10 mg QD), TAC (3 mg BID, goal 8–10 ng/mL), MMF (1,000 mg BID); Prophylaxis: Valganciclovir (CMV), trimethoprim-sulfamethoxazole (PCP)1st transplant: Chronic antibody-mediated rejection (AMR) and recurrent T cell-mediated rejection (TCMR), leading to irreversible graft loss at 88 months. Retransplant: Grade III TCMR at 3 and 4 months post-retransplant, treated with STR and alemtuzumabN/ANoCMV viremia post-retransplant (treated with valganciclovir) significant intraoperative bleeding (2.5 L blood loss)N/AN/A
Neuromotor Speech Recovery Across Different Behavioral Speech Modifications in Individuals Following Facial TransplantationEshghi et al.2021Early group: 2 months; Late group: 42 monthsN/AN/AN/AN/AN/AN/AN/A
Face Transplant: Current Update and First Canadian ExperienceGovshievich et al.202118 monthsN/AN/AN/AN/AMucormycosis of left thighN/AN/A
Facial Nerve Revascularization Strategies in Facial RestorationKhajuria et al.20226 yearsNo requirementN/AN/AN/AFlap necrosis, hematomaN/ANo
Re-cognizing the new self: The neurocognitive plasticity of self-processing following facial transplantationAzevedo et al.20222 yearsN/AN/AN/AYes [repair of floor-of-mouth & palatal wound dehiscence on POD 11, internal fixation of left mandibular nonunion, b/l canthoplasty & complex tissue rearrangement lower eyelids & cheeks (POD 108), left medial canthoplasty & complex tissue rearrangement of left lower eyelid (POD 248))N/AN/AN/A
Facial Expression after Face Transplant: An International Face Transplant Cohort ComparisonDorante et al.20233.6 years ± 2.2 monthsN/AN/AN/AYes, nerve transfer revisionN/AN/AYes, e.g., masseter-to-facial nerve transfer
Anatomical study of trigeminal-facial nerve communications: Application to facial transplant surgeryIwai et al.2025N/AN/AN/AN/AN/AN/AN/AN/A

Complications after facial nerve reconstruction.

N/A, not available/not applicable; m, male; f, female; FN, facial nerve; ATG, antithymocyte globulin; TAC, tacrolimus; MMF, mycophenolate mofetil; PDN, prednisone; STR, steroid therapy; MAB, monoclonal antibody; MPDN, methylprednisolone; Tx, treatment; Pt/Pts, patient/patients; Ab, antibody; TMG, Thymoglobulin; POD, postoperative day; IO, intraoperative; PO, postoperative; CMV, cytomegalovirus; HSV, herpes simplex virus; FT, facial transplantation; Sx, surgery; b/l, bilateral; Le Fort III, anatomical classification of midface fracture used for orientation in facial surgery; PCP, Pneumocystis pneumonia; BID, twice daily.

3.5 Perspectives and preclinical advances

Preclinical evidence was scarce and limited to rodent and porcine models. Overall, study results supported the clinical evidence that meaningful FN regeneration can be achieved when both motor and sensory nerves are coapted. In a rat model, vascularized mystacial pad flaps transplanted across a full MHC mismatch demonstrated successful reinnervation when motor (buccal, marginal mandibular, zygomatic) and sensory (infraorbital) nerves were repaired. These flaps exhibited restored whisker-defense reflexes, ENG amplitudes around 2 mV, and myelinated fibers on histology six weeks postoperatively, while non-repaired controls showed no electrical activity. In a hemiface transplant model of rats, only grafts with both FN branch and infraorbital coaptation demonstrated motor potentials and cortical activity in the barrel cortex, whereas denervated flaps showed none. At last, one study using a heterotopic midface transplant (nose, premaxilla, and lip) of rats with nerve coaptation showed long-term survival (>100 days) in both isografts and immunosuppressed allografts. These exhibited somatosensory- and motor-evoked potential latencies reaching 67% and 70% of native values, respectively, alongside viable bone on CT (Table 4).

Table 4

DOITitleAuthorYear of publicationStudy typeAnimal modelInterventionObjective of interventionComparison groupsOutcome
DOI: 10.1111/j.1432-2277.2009.01032.xA new composite midface allotransplantation model with sensory and motor reinnervationZor et al.2009In-vivoInbred rats (8- to 10-week-old); recipient: Lewis (RT1^l), donor: Lewis (RT1^l) and Lewis-Brown Norway (LBN, RT1^l + n)Composite midface graft (including nose, lower lip, masseter, and premaxilla with hard palate and teeth) was harvested on the donor's carotid artery and jugular vein, incorporating both infraorbital (sensory) and FN (motor) branches; heterotopic transplantation to the recipient's inguinal region with vascular anastomoses to femoral vessels and nerve coaptations (infraorbital to saphenous, FN to femoral); cyclosporine A monotherapyExtension of the rat face transplant model via a composite midface allograft including infraorbital and facial nerves plus bone and soft tissue, enabling long-term functional recovery assessment through CT, SSEP, and MEPGroup I: Anatomic study (model development/dissection, n = 3); Group II: Isograft transplants (between genetically identical Lewis rats, n = 5); Group III: Allograft transplants (from Lewis-Brown Norway donors to Lewis recipients under CsA monotherapy, n = 5)All composite midface grafts survived >100 days with confirmed vascularization (microangiography) and bone viability (CT). Motor function returned by day 20 and reached ∼70% of normal FN values; sensory recovery achieved ∼67% of normal ION latencies. Imaging and electrophysiology confirmed successful reinnervation and functional restoration
DOI: 10.1097/SAP.0b013e31819031efSensorimotor recovery after partial facial (mystacial pad) transplantation in ratsLandin et al.2009In-vivoInbred rats; recipient: Wistar-Lewis (RT1 L), donor: Lewis-Brown-Norway (RT1ln)Partial facial transplantation using a mystacial pad flap based on facial vessels, with microvascular anastomoses; two study groups: i) with nerve repair (including bucolabial, marginal mandibular, zygomatico-orbital FN branches and the infraorbital nerve) and ii) without nerve repairInvestigation of nerve repair's impact on sensorimotor recovery in mystacial pad allotransplants, using clinical, neurophysiological, and histologic outcome measuresMultiple experimental groups were created, with the main comparison between non-neurotized alloflaps (VIa) and neurotized alloflaps with nerve repair (VIb); additional isograft and flap groups assessed graft viability and takeAverage operative time was ∼3.5 h with an 87.5% survival rate at 8 weeks. Flaps with nerve repair (VIb) showed significant sensorimotor recovery on ENG, EMG, and histology, while non-repaired flaps (VIa) showed signs of denervation
DOI: 10.1097/prs.0b013e318191bca2A model for functional recovery and cortical reintegration after hemifacial composite tissue allotransplantationWashington et al.2009In-vivoInbred rats (8- to 10-week-old); recipient: Lewis (RT1 L), donor: Brown-Norway (RT1n)Hemifacial transplant including mystacial pad with microsurgical vascular anastomoses and motor (buccal, marginal mandibular) and sensory (infraorbital) nerve coaptations; groups with and without nerve repair; allografts received cyclosporine ADevelopment of a functional rat hemifacial transplant model that allows studying motor and sensory recovery—including cortical reintegrationGroup 1: Syngeneic transplants with motor and sensory nerve appositions; Group 2: Syngeneic transplants without nerve appositions; Group 3: Allogeneic transplants with nerve appositions (with cyclosporine A immunosuppression)Groups with nerve appositions (1 and 3) showed significant motor (whisking, conduction) and sensory (cortical response) recovery, while non-neurotized grafts (group 2) lacked electrical or cortical activity
DOI: 10.1097/SCS.0000000000002449Surgical Technique of Hemi-Face Transplant: A New Model of TrainingCunico et al.2016In-vivoSeven swines (Sus scrofa domesticus, Landrace line, approximately 60 days old and weighing between 10 and 20 kilograms)Excision and immediate reimplantation of the left hemiface at the same site using microsurgical vascular and nerve anastomoses under magnificationDevelopment of a reproducible swine hemifacial transplant model for surgical training, focusing on microsurgical reconstruction of vessels and nervesComparison of immediate post-euthanasia procedures vs. delayed procedures after cooling to evaluate differences in hemostasis and tissue handlingThe procedure averaged 4.5 h with consistent reproducibility; anatomical and technical challenges—such as obesity and vascular variations (e.g., caudal auricular artery)—were noted, confirming the model's suitability for microsurgical training

Preclinical evidence on facial nerve reconstruction in facial VCA.

DOI, Digital Object Identifier; FN, Facial Nerve; CT, Computed Tomography; SSEP, Somatosensory-Evoked Potential; MEP, Motor-Evoked Potential; ENG, Electroneurography; EMG, Electromyography; ION, Infraorbital Nerve; CsA, Cyclosporine A.

4 Discussion

FN reconstruction is a critical determinant of functional success in FVCA. While surgical advancements have rendered full or partial face transplantation technically feasible, the restoration of dynamic facial expression remains one of the most complex and unpredictable aspects of the procedure (32). Emerging patterns from the available evidence suggest a preliminary, clinically relevant framework in which allograft extent, reconstructive strategy, neuromuscular recovery phase, and immunologic stability function as interdependent domains shaping postoperative outcomes. The intricate nature of FN injury and repair in FVCA necessitates individualized coaptation strategies, including direct repair, nerve grafting, and targeted nerve transfers, to address anatomical and physiological challenges (33). Unlike conventional facial nerve surgery, FVCA involves donor–recipient anatomical mismatches, variable nerve diameters, and the need to coordinate reinnervation across multiple composite tissue units. Additionally, immunologic factors unique to allotransplantation, such as rejection episodes and the effects of long-term immunosuppression, can directly influence nerve regeneration and graft viability. The requirement to achieve both motor and sensory reinnervation across a transplanted facial framework further compounds the complexity of achieving predictable functional outcomes. Therefore, this discussion aims to compare FN reconstruction in FVCA to established approaches in conventional FN and peripheral nerve repair and provide a critical analysis of the spectrum of techniques employed in both clinical and preclinical studies. Thereby, this review seeks to highlight current outcomes and explore emerging strategies to enhance reinnervation and optimize long-term functional recovery of the FN following FVCA.

In our study, we found direct coaptation of FN branches to be the most common repair strategy, often resulting in partial functional recovery within as little as 3–6 months. EMG evidence supported gradual reinnervation, though outcomes varied, and synkinesis or revision procedures were occasionally required. Surgical complications further influenced long-term FN function, highlighting the need for refined FN reconstruction techniques and outcome assessment methods in FVCA (Figure 2).

Figure 2

When comparing this to literature, FN reconstruction in FVCA presents unique technical and biological challenges that distinguish it from conventional FN and peripheral nerve repair (, 34).

4.1 Technical factors influencing recovery

FN reconstruction in FVCA presents distinct technical challenges compared with conventional FN or peripheral nerve repair. In standard FN surgery, such as after trauma or oncologic resection, tension-free, end-to-end coaptation remains the gold standard and typically yields meaningful recovery within 3–6 months (35, 36). When direct coaptation is not feasible, interpositional autografts (sural or great auricular nerve) or motor nerve transfers (hypoglossal–FN, masseteric–FN) are well-established options, with many patients achieving HB III–IV function (3739). In FVCA, however, the reconstructive environment is inherently more complex. Surgeons must contend with donor–recipient anatomical mismatch, variable branch orientation, and the need to integrate nerves within a composite tissue allograft (, 40, 41). Although direct coaptation remains preferred when feasible, the risk of misalignment or distal branch mismatch is greater than in isolated FN reconstruction, even more so when interpositional grafts are required (4244). Donor nerves also traverse composite soft tissue and skeletal components, making successful recovery dependent not only on microsurgical precision but also on the viability and integration of the transplanted neuromuscular units (45, 46). Recovery timelines differ accordingly. While conventional FN repairs often show substantial motor recovery within 6–12 months, FVCA recovery is more variable. Initial motion may occur around 3–6 months, but EMG evidence suggests that reinnervation may continue for 24–36 months or longer (47, 48). Prolonged recovery likely reflects greater regenerative distances, pre-existing scarring, and delayed reconstruction as well as technical and biologic constraints unique to FVCA (49, 50).

4.2 Immunological factors influencing recovery

Complications such as synkinesis, asymmetric movement, and incomplete motor recovery are common to both standard FN repair and VCA. However, immunologic dynamics represent one of the most consequential differences between FVCA and conventional FN repair (51). FVCA recipients frequently experience acute or subclinical rejection episodes in the early postoperative period, often treated with high-dose steroids or adjustments to tacrolimus therapy (, 52, 53). Complications such as synkinesis, asymmetric movement, and incomplete activation occur in both settings, but in FVCA these issues may be compounded by rejection-related injury or ischemic episodes. As a result, revision procedures, including nerve re-coaptation, static suspension, or supplementary reanimation techniques, are required more frequently in FVCA than conventional nerve repairs (54). Thus, unlike isolated FN repair, functional recovery in FVCA depends on achieving and maintaining not only microsurgical success but also long-term immunologic stability of the transplanted neuromuscular tissue (55).

4.3 Rehabilitative and outcome-assessment factors

Despite the surgical and immunologic complexity, outcome measurements in FVCA remained inconsistent. Unlike standard FN repair, where validated scales such as the HB grading system, Sunnybrook Facial Grading System (i.e., a recognized tool for assessing facial palsy with a total composite score between 0 and 100), and FDI are routinely used, VCA literature often relies on qualitative assessments or unvalidated photographic analysis. Broader implementation of validated scales, such as the FDI and facial tracking software such as FaceReader™, Emotrics™ or Emotient™, would allow for more objective and reproducible assessment of motor recovery and patient satisfaction (5658). Additionally, digital tools like the eFACE scale have shown promise as intuitive, clinician-friendly instruments for standardized facial function evaluation across platforms (59). In conclusion, literature highlighted that while FN reconstruction in FVCA borrows from established principles in peripheral and FN surgery, it requires significant adaptation to the immunologic and anatomical complexities of composite tissue transplantation. Furthermore, optimizing surgical outcomes depended on precise microsurgical technique, consistent intraoperative neuromonitoring, and long-term rehabilitative strategies in both FVCA and conventional FN reconstruction.

4.4 Emerging patterns and toward a clinically actionable framework

Despite the heterogeneity of available evidence, several higher-order themes emerge that may inform a preliminary framework for understanding facial nerve reconstruction in FVCA. First, across studies, nerve coaptation strategy, whether direct, graft-assisted, or dual-level, appears consistently aligned with the extent of allograft complexity, suggesting a pattern in which more extensive transplants necessitate more elaborate reconstructive algorithms. Second, functional recovery trajectories demonstrate a relatively stable temporal pattern: early EMG activity typically emerges around 1–6 months, voluntary motion around 3–9 months, and continued maturation up to 3 years, indicating a predictable multi-phased recovery course that may aid in clinical counseling and postoperative planning. Third, cases with integrated motor and sensory coaptation (both in humans and preclinical models) generally exhibit more robust reinnervation, hinting at a potential “sensorimotor synergy” that warrants further exploration as a guiding reconstructive principle. Fourth, complication profiles consistently underscore the interplay between immunologic stability and the durability of nerve repair, suggesting that FN-related outcomes may benefit from risk-stratified immunosuppression and early detection strategies for rejection. Together, these themes suggest an emerging conceptual framework in which (1) allograft extent, (2) reconstructive strategy, (3) neuromuscular recovery phase, and (4) immunologic stability function as interdependent domains shaping outcomes. Although preliminary, this pattern-based synthesis may serve as the basis for future standardized reporting, comparative studies, and the development of actionable treatment algorithms in facial nerve reconstruction following FVCA. Linking specific reconstructive approaches to detailed functional outcomes in future studies might further strengthen this framework and help lay the groundwork for targeted investigations evaluating the effectiveness of distinct surgical strategies.

4.5 Summary and outlook

Moving forward, several strategies could potentially address the current challenges in FN reconstruction after FVCA. Principles from standard FN and peripheral nerve repair, such as direct coaptation, nerve grafting, and motor nerve transfers, should further be successfully adapted to the VCA setting if they are carefully tailored to the specific anatomical and immunologic environment of the transplant. In this context, innovative approaches like “supercharging”, as recently demonstrated in the Epta-innervation technique using up to seven donor nerves, may offer additional benefits in enhancing reinnervation and improving symmetry in mimetic function (60). Preoperative planning with detailed donor–recipient nerve matching and intraoperative nerve stimulation may enhance surgical precision and improve initial outcomes. Recovery trajectories in FVCA might be improved through early postoperative rehabilitation, including facial retraining, functional electrical stimulation, and targeted biofeedback. These strategies, which are well established in conventional FN rehabilitation, could support more coordinated and symmetric reinnervation (61).

At the same time, confounding factors unique to VCA, particularly the impact of systemic immunosuppression on nerve healing (e.g., tacrolimus), must be considered (62). Immunosuppressive regimens, while necessary to prevent graft rejection, might impair axonal regeneration and synaptic plasticity. Future modifications, such as localized immunosuppression or novel immunomodulatory protocols, could help mitigate these effects, although more evidence is needed. Moreover, translational research, including preclinical animal models, cadaveric nerve mapping studies, and advanced imaging analyses, might provide valuable insights into optimizing nerve coaptation strategies and improving functional outcomes. Promising clinical data also support the use of connector-assisted allograft techniques, such as Avance® nerve allografts combined with AxoGuard® sleeves, which have demonstrated high rates of functional sensory recovery, particularly in immediate reconstruction of the inferior alveolar nerve following mandibular resection (63). Establishing multicenter registries and applying standardized outcome measures, such as the FDI scale, and EMG tracking, could enable more reliable comparisons across centers and support more individualized, evidence-based treatment planning. In parallel, future strategies should prioritize the identification of predictive factors for favorable or poor outcomes, such as patient-specific variables, surgical timing, or nerve gap characteristics, which could guide clinical decision-making and help stratify patients for tailored interventions. Ultimately, careful adaptation of established surgical principles, combined with advances in immunologic management and preclinical research, could lead to more predictable nerve regeneration and better long-term facial function for patients undergoing FVCA.

5 Limitations

This systematic review has several limitations that must be acknowledged. First, the inherent heterogeneity of included studies limited the ability to perform a quantitative meta-analysis. Variability in study design, nerve reconstruction techniques, outcome assessment tools, and reporting time points posed challenges for direct comparisons and synthesis. Rehabilitation protocols also differed substantially across studies, further contributing to variability in reported outcomes. Additionally, a significant proportion of included studies were case reports or small case series, which introduces selection bias and limits the generalizability of findings. Second, the methodological quality of included clinical studies was overall moderate, with many lacking prospective data collection, standardized outcome measures, or comprehensive follow-up. The use of diverse and sometimes non-validated tools to assess functional recovery, such as subjective photographic analysis or qualitative descriptions, may have introduced measurement bias and prevented robust comparisons. Moreover, long-term electromyographic follow-up was rarely standardized or consistently reported, limiting the ability to compare reinnervation trajectories across interventions. In addition, many studies did not report motor and sensory outcomes separately or with sufficient detail, preventing a systematic distinction between these domains despite their relevance to comprehensive facial nerve reconstruction. Similarly, insufficient reporting on reconstructive strategies in relation to functional outcomes limited our ability to meaningfully correlate technique selection with recovery patterns, representing an important area for improvement in future studies. Third, donor and recipient characteristics were often incompletely reported, particularly regarding nerve diameter match, injury chronicity, and delay from injury to transplantation. These variables could substantially influence reinnervation success but were not systematically addressed. Similarly, the impact of immunosuppressive regimens on nerve regeneration could not be assessed due to inconsistent reporting of dose, duration, and complications. Fourth, the review may have been subject to publication bias, as negative or poor-outcome cases are less frequently published, especially in high-impact journals. This could lead to an overestimation of the effectiveness of certain surgical strategies. Finally, while efforts were made to include all relevant literature, it is possible that some pertinent studies were missed due to limitations in database indexing or language restrictions. Although the search strategy was broad and supplemented by manual reference checks, only English-language, peer-reviewed publications were included. Future reviews may benefit from international registry data, standardized reporting templates, prospective multicenter studies, and harmonized rehabilitation and EMG follow-up protocols to improve the quality, reproducibility, and comparability of findings.

6 Conclusion

FN reconstruction is a key determinant of functional success in FVCA. This review highlights the predominance of direct coaptation and the gradual integration of advanced techniques such as motor nerve transfers and dual level coaptation. While outcomes are encouraging, they remain variable and are shaped by surgical precision, immunologic factors, and rehabilitation. FN reinnervation is often achievable but tends to be partial and delayed. Greater use of standardized assessment tools—such as the HB Grading System, FDI, and EMG—could improve comparability across studies. Conventional nerve repair strategies may be adapted to the FVCA setting with thoughtful anatomical and immunologic tailoring. Progress will depend on translational research to understand nerve healing under immunosuppression, optimize coaptation protocols, and validate rehabilitation strategies. Multicenter data, harmonized outcome reporting, and preclinical models will be essential for advancing FN repair and improving long-term function and quality of life after FVCA.

Statements

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

Author contributions

LK: Writing – review & editing, Writing – original draft. TN: Writing – review & editing, Conceptualization, Writing – original draft. RM: Writing – original draft, Investigation, Writing – review & editing. SJ: Writing – review & editing, Software, Writing – original draft. TS: Writing – review & editing, Writing – original draft, Data curation. CC: Writing – review & editing, Methodology. CF: Writing – review & editing, Supervision. AK: Formal analysis, Writing – review & editing. GH: Validation, Writing – review & editing. MH: Visualization, Writing – original draft. SK: Writing – original draft, Project administration. NN: Writing – review & editing, Conceptualization. JV: Writing – review & editing, Supervision. AL: Supervision, Validation, Writing – review & editing.

Funding

The author(s) declared that financial support was not received for this work and/or its publication.

Acknowledgments

The graphical abstract and Figure 2 were created with BioRender.com, and we gratefully acknowledge BioRender for providing their illustration platform.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

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Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fsurg.2026.1738957/full#supplementary-material

References

  • 1.

    DevauchelleBBadetLLengeléBMorelonETestelinSMichalletMet alFirst human face allograft: early report. Lancet. (2006) 368(9531):2039. 10.1016/s0140-6736(06)68935-6

  • 2.

    KnoedlerLHochCCKnoedlerSKlimitzFJSchaschingerTNiedereggerTet alObjectifying aesthetic outcomes following face transplantation—the AI research metrics model (CAARISMA ® ARMM). J Stomatol Oral Maxillofac Surg. (2025) 126(6):102277. 10.1016/j.jormas.2025.102277

  • 3.

    KnoedlerLHochCCSchaschingerTNiedereggerTKnoedlerSFestbaumCet alObjective and automated facial palsy grading and outcome assessment after facial palsy reanimation surgery—a prospective observational study. J Stomatol Oral Maxillofac Surg. (2024) 126:102211. 10.1016/j.jormas.2024.102211

  • 4.

    KnoedlerLKauke-NavarroMKnoedlerSNiedereggerTHofmannEHeilandMet alOral health and rehabilitation in face transplant recipients—a systematic review. Clin Oral Investig. (2025) 29(1):47. 10.1007/s00784-024-06078-3

  • 5.

    KlimitzFJAmanMNeubauerHStolleAZiegenthalerHNiedereggerTet alPost-Traumatic stress disorder (PTSD) is associated with increased physical skin symptom burden following severe burn injuries: subgroup analysis of a multicenter prospective cohort. Eur Burn J. (2025) 6(3):43. 10.3390/ebj6030043

  • 6.

    NiedereggerTSchaschingerTKarakasEAshgarMKnoedlerLKlimitzFet alPsychological impact and stigma after facial burns: a systematic review. J Plast Reconstr Aesthet Surg. (2025). 10.1016/j.bjps.2025.10.010

  • 7.

    AudolfssonTRodríguez-LorenzoAWongCChengAKildalMNowinskiDet alNerve transfers for facial transplantation: a cadaveric study for motor and sensory restoration. Plast Reconstr Surg. (2013) 131(6):123140. 10.1097/PRS.0b013e31828bd394

  • 8.

    HohmanMHDe JesusO. Facial Nerve Repair. StatPearls. StatPearls Publishing Copyright © 2025, StatPearls Publishing LLC (2025).

  • 9.

    GordinELeeTSDucicYArnaoutakisD. Facial nerve trauma: evaluation and considerations in management. Craniomaxillofac Trauma Reconstr. (2015) 8(1):113. 10.1055/s-0034-1372522

  • 10.

    AnderlH. Reconstruction of the face through cross-face-nerve transplantation in facial paralysis. Chirurgia Plastica. (1973) 2(1):1745. 10.1007/BF00280913

  • 11.

    ManktelowRTTomatLRZukerRMChangM. Smile reconstruction in adults with free muscle transfer innervated by the masseter motor nerve: effectiveness and cerebral adaptation. Plast Reconstr Surg. (2006) 118(4):88599. 10.1097/01.prs.0000232195.20293.bd

  • 12.

    KehrerAEngelmannSKnoedlerLKleinSMAnkerAMHeidekruegerPet alThe masseteric nerve for facial reanimation: macroscopic and histomorphometric characteristics in 106 human cadavers and comparison of axonal ratio with recipient nerves. J Craniomaxillofac Surg. (2024) 52(1):813. 10.1016/j.jcms.2023.09.001

  • 13.

    KehrerARueweMPlatz Batista da SilvaNLonicDHeidekruegerPIKnoedlerSet alUsing high-resolution ultrasound to assess post-facial paralysis synkinesis-machine settings and technical aspects for facial surgeons. Diagnostics (Basel). (2022) 12(7):1650. 10.3390/diagnostics12071650

  • 14.

    KnoedlerLBaecherHKauke-NavarroMPrantlLMachensH-GScheuermannPet alTowards a reliable and rapid automated grading system in facial palsy patients: facial palsy surgery meets computer science. J Clin Med. (2022) 11(17):4998. 10.3390/jcm11174998

  • 15.

    KehrerAHollmannKSKleinSMAnkerAMTammERPrantlLet alHistomorphometry of the sural nerve for use as a CFNG in facial reanimation procedures. J Clin Med. (2023) 12(14):4627. 10.3390/jcm12144627

  • 16.

    GeogheganLAl-KhalilMScarboroughAMurrayAIssaF. Pre-transplant management and sensitisation in vascularised composite allotransplantation: a systematic review. J Plast Reconstr Aesthet Surg. (2020) 73(9):1593603. 10.1016/j.bjps.2020.05.010

  • 17.

    MilekDReedLTEchternachtSRShanmugarajahKCetruloCLLellouchAGet alA systematic review of the reported complications related to facial and upper extremity vascularized composite allotransplantation. J Surg Res. (2023) 281:16475. 10.1016/j.jss.2022.08.023

  • 18.

    SiemionowM. The decade of face transplant outcomes. J Mater Sci Mater Med. (2017) 28(5):64. 10.1007/s10856-017-5873-z

  • 19.

    KnoedlerLFenskeJSchaschingerTNiedereggerTGonzalezJCetruloCLet alAnalyzing the candidate pool for vascularized composite allotransplantation—a multi-center OPTN study with a focus on face transplant candidates. J Craniomaxillofac Surg. (2025) 53(9):14317. 10.1016/j.jcms.2025.05.023

  • 20.

    DiazRCCervenkaBBrodieHA. Treatment of temporal bone fractures. J Neurol Surg B Skull Base. (2016) 77(5):41929. 10.1055/s-0036-1584197

  • 21.

    HuelsboemerLKauke-NavarroMBoroumandSParikhNHosseiniHYuCTet alTen-year follow-up after face transplantation—A single-center retrospective cohort study. Am J Transplant. (2025) 25(3):61122. 10.1016/j.ajt.2024.10.007

  • 22.

    PomahacBPribazJJBuenoEMSiskGCDiaz-SisoJRChandawarkarAet alNovel surgical technique for full face transplantation. Plast Reconstr Surg. (2012) 130(3):54955. 10.1097/PRS.0b013e31825dc25c

  • 23.

    SwansonJWYuJWTaylorJAKovachSKanchwalaSLantieriL. The retroauricular approach to the facial nerve trunk. J Craniofac Surg. (2017) 28(2):34751. 10.1097/scs.0000000000003290

  • 24.

    SeixasSFForteGCMagnusGAStanhamVMattielloRSilvaJB. Effect of tacrolimus and cyclosporine immunosuppressants on peripheral nerve regeneration: systematic review and meta-analysis. Rev Bras Ortop (Sao Paulo). (2022) 57(2):20713. 10.1055/s-0041-1736467

  • 25.

    Kauke-NavarroMTchiloembaBHaugVKollarBDiehmYSafiA-Fet alPathologies of oral and sinonasal mucosa following facial vascularized composite allotransplantation. J Plast Reconstr Aesthet Surg. (2021) 74(7):156271. 10.1016/j.bjps.2020.11.028

  • 26.

    KnoedlerLNiedereggerTSchaschingerTFenskeJMuruganVKnoedlerSet alBio-Boosting transplants: a systematic review on biopolymers in vascular composite allotransplantation. Front Immunol. (2025) 16:1645261. 10.3389/fimmu.2025.1645261

  • 27.

    NiedereggerTSchaschingerTBrandtJKnoedlerLKnoedlerSPalackicAet alThe burn repair molecule? Evaluating FGF-21 in thermal injury—a systematic review. Burns. (2025) 52(1):107785. 10.1016/j.burns.2025.107785

  • 28.

    WellsGASheaBO’ConnellDPetersonJWelchVLososMTugwellP. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses (2014).

  • 29.

    HooijmansCRRoversMMde VriesRBMLeenaarsMRitskes-HoitingaMLangendamMW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. (2014) 14(1):43. 10.1186/1471-2288-14-43

  • 30.

    BurnsPBRohrichRJChungKC. The levels of evidence and their role in evidence-based medicine. Plast Reconstr Surg. (2011) 128(1):30510. 10.1097/PRS.0b013e318219c171

  • 31.

    HouseJWBrackmannDE. Facial nerve grading system. Otolaryngol Head Neck Surg. (1985) 93(2):1467. 10.1177/019459988509300202

  • 32.

    KnoedlerLSchaschingerTNiedereggerTHundeshagenGPanayiACCetruloCLet alMulti-Center outcome analysis of 16 face transplantations—a retrospective OPTN study. Original research. Transpl Int. (2025) 38:14107. 10.3389/ti.2025.14107

  • 33.

    La PadulaSPensatoRPizzaCCoianteERoccaroGLongoBet alFace transplant: indications, outcomes, and ethical issues-where do we stand?J Clin Med. (2022) 11(19):5750. 10.3390/jcm11195750

  • 34.

    LongoBAlbertiFBPomahacBPribazJJMeningaudJ-PLengeléBet alInternational consensus recommendations on face transplantation: a 2-step delphi study. Am J Transplant. (2024) 24(1):10414. 10.1016/j.ajt.2023.08.023

  • 35.

    KnoedlerLHochCCBaecherHGeldnerBNiedereggerTLellouchAGet alTherapeutic outcomes in 691 angiosarcomas of the head and neck-A retrospective SEER study. J Craniofac Surg. (2025) 36(5):16616. 10.1097/scs.0000000000010937

  • 36.

    KnoedlerLFestbaumCDeanJBaecherHde LambertyeGMaulMet alDiagnosing facial synkinesis using artificial intelligence to advance facial palsy care. Sci Rep. (2025) 15(1):24686. 10.1038/s41598-025-08548-4

  • 37.

    GrinsellDKeatingCP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int. (2014) 2014:698256. 10.1155/2014/698256

  • 38.

    KaiserRUllasGHavránekPHomolkováHMiletínJTicháPet alCurrent concepts in peripheral nerve injury repair. Acta Chir Plast. Fall. (2017) 59(2):8591.

  • 39.

    PinkiewiczMDorobiszKZatońskiT. A comprehensive approach to facial reanimation: a systematic review. J Clin Med. (2022) 11(10):2890. 10.3390/jcm11102890

  • 40.

    GiatsidisGSinhaIPomahacB. Reflections on a decade of face transplantation. Ann Surg. (2017) 265(4):8416. 10.1097/sla.0000000000001760

  • 41.

    LantieriLHivelinMAudardVBenjoarMDMeningaudJPBellivierFet alFeasibility, reproducibility, risks and benefits of face transplantation: a prospective study of outcomes. Am J Transplant. (2011) 11(2):36778. 10.1111/j.1600-6143.2010.03406.x

  • 42.

    BiglioliFFrigerioAColomboVCollettiGRabbiosiDMortiniPet alMasseteric-facial nerve anastomosis for early facial reanimation. J Craniomaxillofac Surg. (2012) 40(2):14955. 10.1016/j.jcms.2011.03.005

  • 43.

    BiglioliFColomboVRabbiosiDTarabbiaFGiovandittoFLozzaAet alMasseteric-facial nerve neurorrhaphy: results of a case series. J Neurosurg. (2017) 126(1):3128. 10.3171/2015.12.Jns14601

  • 44.

    Dalla ToffolaEPaveseCCeciniMPetrucciLRicottiSBejorMet alHypoglossal-facial nerve anastomosis and rehabilitation in patients with complete facial palsy: cohort study of 30 patients followed up for three years. Funct Neurol. (2014) 29(3):1837.

  • 45.

    YanYMacEwanMRHunterDAFarberSNewtonPTungTHet alNerve regeneration in rat limb allografts: evaluation of acute rejection rescue. Plast Reconstr Surg: (2013) 131(4):499e511E. 10.1097/PRS.0b013e31828275b7

  • 46.

    YanYWoodMDMooreAMSnyder-WarwickAKHunterDANewtonPet alRobust axonal regeneration in a mouse vascularized composite allotransplant model undergoing delayed tissue rejection. Hand (N Y). (2016) 11(4):45663. 10.1177/1558944715620791

  • 47.

    GriffinMFMalahiasMHindochaSWasimSK. Peripheral nerve injury: principles for repair and regeneration. Open Orthop J. (2014) 8:199203. 10.2174/1874325001408010199

  • 48.

    LantieriLGrimbertPOrtonneNSuberbielleCBoriesDGil-VernetSet alFace transplant: long-term follow-up and results of a prospective open study. Lancet. (2016) 388(10052):1398407. 10.1016/s0140-6736(16)31138-2

  • 49.

    KaukeMPanayiASafiAFHaugVPerryBKollarBet alFull facial retransplantation in a female patient—technical, immunologic and clinical considerations. Am J Transplant. (2021) 21(10):347280. 10.1111/ajt.16696

  • 50.

    KaukeMSafiAFPanayiACPalmerWJHaugVKollarBet alA systematic review of immunomodulatory strategies used in skin-containing preclinical vascularized composite allotransplant models. J Plast Reconstr Aesthet Surg. (2022) 75(2):586604. 10.1016/j.bjps.2021.11.003

  • 51.

    KnoedlerLNiedereggerTSchaschingerTHundeshagenGGonzalezJKauke-NavarroMet alImmunosuppressive and antiinfectious regimens in vascular composite allograft recipients–A systematic review. Front Transplant. (2025) 4:1714886. 10.3389/frtra.2025.1714886

  • 52.

    BarretJPGavaldàJBuenoJNuvialsXPontTMasnouNet alFull face transplant: the first case report. Ann Surg. (2011) 254(2):2526. 10.1097/SLA.0b013e318226a607

  • 53.

    KnoedlerLKlimitzFJHuelsboemerLNiedereggerTSchaschingerTBoroumandSet alExperimental swine models for vascularized composite allotransplantation and immunosuppression: a systematic review and case report of a novel heterotopic hemifacial swine model. Transpl Int. (2025) 38:14520. 10.3389/ti.2025.14520

  • 54.

    EisenhardtSUEisenhardtNAThieleJRStarkGBBannaschH. Salvage procedures after failed facial reanimation surgery using the masseteric nerve as the motor nerve for free functional gracilis muscle transfer. JAMA Facial Plast Surg. (2014) 16(5):35963. 10.1001/jamafacial.2014.163

  • 55.

    DeanJNiedereggerTSchaschingerTHundeshagenGJeljeliMCetruloCLJret alThe risk profile of face transplant versus other types of vascularized composite allotransplantation surgery–a retrospective multi-center analysis. Available at SSRN 5165075. 10.2139/ssrn.5165075

  • 56.

    VanSwearingenJMBrachJS. The facial disability Index: reliability and validity of a disability assessment instrument for disorders of the facial neuromuscular system. Phys Ther. (1996) 76(12):128898. 10.1093/ptj/76.12.1288

  • 57.

    NeelyJGCherianNGDickersonCBNedzelskiJM. Sunnybrook facial grading system: reliability and criteria for grading. Laryngoscope. (2010) 120(5):103845. 10.1002/lary.20868

  • 58.

    ZhuABoonipatTCherukuriSBiteU. Defining standard values for FaceReader facial expression software output. Aesthetic Plast Surg. (2024) 48(5):78592. 10.1007/s00266-023-03468-y

  • 59.

    BanksCAJowettNAzizzadehBBeurskensCBhamaPBorschelGet alWorldwide testing of the eFACE facial nerve clinician-graded scale. Plast Reconstr Surg. (2017) 139(2):491e8e. 10.1097/prs.0000000000002954

  • 60.

    BiglioliFBolognesiFTarabbiaFLozzaACupelloSPreviteraAet alEpta-innervation for facial reanimation: seven donor nerves to extremize the concept of multiple innervation and supercharging. J Craniomaxillofac Surg. (2025) 53(9):141721. 10.1016/j.jcms.2025.05.009

  • 61.

    Rodríguez-LorenzoATzouC-HJ. Principles of facial nerve reconstruction. In: TzouC-HJRodríguez-LorenzoA, editors. Facial Palsy: Techniques for Reanimation of the Paralyzed Face. Cham: Springer International Publishing (2021). p. 5569.

  • 62.

    DaeschlerSCFeinbergKHarhausLKneserUGordonTBorschelGH. Advancing nerve regeneration: translational perspectives of tacrolimus (FK506). Int J Mol Sci. (2023) 24(16):12771. 10.3390/ijms241612771

  • 63.

    MiloroMCallahanNFMarkiewiczMRKolokythasAMolesSLChakrabortyK. Immediate Inferior alveolar nerve reconstruction with ablative mandibular resection results in functional sensory recovery. J Oral Maxillofac Surg. (2024) 82(1):12633. 10.1016/j.joms.2023.09.025

Summary

Keywords

face transplantation, facial nerve reconstruction, functional facial reanimation, nerve coaptation, vascularized composite allotransplantation

Citation

Knoedler L, Niederegger T, Munzinger R, Joshi S, Schaschinger T, Cetrulo Jr. CL, Festbaum C, Kehrer A, Hundeshagen G, Heiland M, Koerdt S, Neckel N, Voss JO and Lellouch AG (2026) Rewiring faces: advances and outcomes in facial nerve reconstruction after facial vascularized composite allotransplantation. Front. Surg. 13:1738957. doi: 10.3389/fsurg.2026.1738957

Received

04 November 2025

Revised

16 December 2025

Accepted

02 January 2026

Published

30 January 2026

Volume

13 - 2026

Edited by

Benedetto Longo, University of Rome Tor Vergata, Italy

Reviewed by

Gennaro D'Orsi, University of Rome Tor Vergata, Italy

Kyle Singerman, University of Kansas Medical Center Research Institute, United States

Updates

Copyright

*Correspondence: Alexandre G. Lellouch

† These authors share first authorship

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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