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

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

Graphical Abstract.

1 Introduction

Facial vascularized composite allografts (FVCA), encompassing both full and partial facial transplants, represents an advanced reconstructive technique for selected patients (1–6). 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 (7).

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 (8). Recent advancements have introduced innovative techniques such as cross-FN grafts and the use of motor nerve transfers (9–15).

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 (16–19). 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 (20–23). 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 (24, 25).

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 (26, 27). 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

Figure 1. PRISMA 2020 flowchart highlighting the study selection process.

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 (28). 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 (29), 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

Table 1. Patient demographics.

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

Table 2. Nerve reconstruction details.

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

Table 3. Complications after facial nerve reconstruction.

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

Table 4. Preclinical evidence on facial nerve reconstruction in facial VCA.

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

Figure 2. Facial-nerve repair in facial VCA—techniques, recovery arc, and clinical impact: direct branch-to-branch coaptation is attempted when feasible, but autografts bridge gaps in roughly two-thirds of facial VCAs; most repairs target the main trunk or its buccal/zygomatic/marginal-mandibular/frontal branches. EMG activity typically returns within 1–6 months, voluntary motion follows by 3–6 months, and function plateaus at 30–38 months—typically improving two to three House-Brackmann grades (ending at III–IV). Benefits include better oral continence, intelligible speech and social reintegration, yet complications—acute rejection, synkinesis and revision surgery—remain common and might blunt overall gains.

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 (2–4, 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 (37–39). 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 (18, 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 (42–44). 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 (22, 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 (56–58). 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.

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

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