A Systematic Review and Meta-Analysis of Nerve Gap Repair: Comparative Effectiveness of Allografts, Autografts, and Conduits : Plastic and Reconstructive Surgery

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Hand/Peripheral Nerve: Original Articles

A Systematic Review and Meta-Analysis of Nerve Gap Repair: Comparative Effectiveness of Allografts, Autografts, and Conduits

Lans, Jonathan MD, PhD1; Eberlin, Kyle R. MD2; Evans, Peter J. MD, PhD3; Mercer, Deana MD4; Greenberg, Jeffrey A. MD5; Styron, Joseph F. MD, PhD6

Author Information
Plastic and Reconstructive Surgery 151(5):p 814e-827e, May 2023. | DOI: 10.1097/PRS.0000000000010088


Traumatic nerve injuries are common, where 1.5% of trauma and up to 15% of upper extremity and lower extremity trauma results in nerve injury.1–5 Commonly affected nerves are the radial and digital nerves in the upper extremity and the peroneal nerve in the lower extremity, predominantly affecting men of working age.4–6 These peripheral nerve injuries can have detrimental effects on quality of life and function.7

Following nerve transection, Wallerian degeneration occurs distally, as myelin is degraded by Schwann cells and macrophages8; proximally, degeneration may occur up to the first node of Ranvier.1 This is followed by axonal regrowth, where exploratory fibers extend from the proximal nerve end and regenerate down endoneurial tubes toward the distal target.9 In the absence of structural support by endoneurial tubes, axons will regrow in a disorganized fashion forming a neuroma.10 However, restoration of function typically only occurs with proper nerve repair.

The ideal nerve repair involves tensionless direct repair of healthy fascicles, which may not be possible following resection of injured nerve ends and the resulting nerve gap. Thus, bridging a nerve gap with a nerve autograft, allograft, or conduit is necessary.1,2 Although commercially available conduits come in lengths up to 30 mm, conduits are typically used for small gap repair. For gaps larger than 30 mm, autograft or allograft are the only options.11

Despite increasing evidence on nerve repairs using autograft, allograft, or conduit, comparisons of outcomes remain sparse. Therefore, the primary aim of this study was to perform a systematic literature review and meta-analysis comparing the meaningful recovery (MR) rates following autograft, allograft, and conduit repairs in nerve gaps larger than 5 mm, in addition to postoperative complications. A secondary aim was to perform a procedure cost analysis if no difference was seen in MR rates.


Literature Search

To identify relevant peer-reviewed studies, a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. The search was conducted in MEDLINE (by means of PubMed) from January of 1980 to March of 2020. Search terms included the following: “peripheral nerves” [Medical Subject Headings terms] OR peripheral nerve[tiab] OR “nerve injury”[tiab] AND (“nerve allograft”[tiab] OR “nerve conduit”[tiab] OR “nerve autograft”[tiab] OR “nerve repair”[tiab] OR “nerve graft”[tiab]). Inclusion criteria were established a priori and used to identify evaluable studies from the search results. Studies must have reported nerve injury type (sensory, mixed, or motor); nerve repair type [autograft, allograft (Avance Nerve Graft, Axogen Corp.), or conduit]; gap length where the nerve repair could be categorized as short gap (>5 to 30 mm; so only commercially available conduits would be evaluated) or long gap (>30 to 70 mm; so only commercially available allograft would be evaluated); and outcomes reported using static two-point discrimination (S2PD), Semmes-Weinstein monofilament (SWMF) testing, and/or Medical Research Council Classification (MRCC), such that MR rates (≥S3/M3) could be determined. Exclusion criteria included nonnerve graft repairs, previously published data, animal studies, non-English language, case reports with fewer than three subjects (to eliminate anecdotal evidence), nerve gaps less than 5 mm or greater than or equal to 110 mm, and vascularized autografts.

Two independent reviewers (J.L. and J.F.S.) evaluated each study for inclusion and exclusion criteria. Data extraction from evaluable studies followed, which was validated independently by both reviewers.

Data Extraction

The following data were extracted using standardized forms and recorded: study design, nerve location (digit, arm, face, lower extremity), nerve type (motor, sensory or mixed), gap length (in millimeters, mean, standard deviation, and range), age (mean, standard deviation, and range), mean follow-up, the number of nerves repaired, donor nerve for autograft, MRCC data, number of patients with MRCC greater than or equal to S3/M3, number of patients with MRCC greater than or equal to S3+/M4, S2PD data, SWMF test data, and complications. The MRCC data were directly extracted as reported or derived from the SWMF data or the S2PD data, as reported previously (Table 1).12–14 All data were verified by secondary clinical reviewers, and inconsistencies were resolved by discussion. The independent reviewers also assessed the quality of the included studies using the Methodological Index for Nonrandomized Studies criteria, and discrepancies were resolved by discussion.15

Table 1. - Conversion of SMWF and 2PDS to MRCC MR
Force (g) Monofilament No.
100–300 6.10–6.65 S0 Loss of protective sensation
10–60 5.07–5.88 S1
4–8 4.56–4.93 S2
0.6–2 3.84–4.31 S3 >15 mm with recovery of pain and touch sensibility
0.16–0.4 3.22–3.61 S3+ 7–15 mm
<0.7 1.62–2.83 S4 ≤6 mm

Nerve Injury Categorization

Nerve injury type was defined as (1) sensory, if only a sensory nerve was repaired; (2) motor, if only a motor nerve was repaired; and (3) mixed, if a mixed motor nerve and a sensory nerve were repaired. Outcomes for mixed nerve repairs were reported in the sensory and/or motor outcomes and were counted separately if both types of outcomes were reported. Nerve repairs were grouped as “short gap” (>5 to ≤30 mm) or “long gap” (>30 to ≤70 mm). This categorization grouping was determined by the average gap length of the study population; when these data were unavailable, the midpoint (median) of the gap length range was used to categorize the nerve repairs as short gap or long gap. When the gap length range was used to determine the gap length categorization, in short gaps, the upper limit of the range could not exceed 70 mm; and for long gaps, the upper limit of the range could not exceed 110 mm. This minimized the exclusion of relevant data that included longer gaps but where the median gap was representative of the short or long gap range. Nerve injuries were categorized as (1) short gap, sensory; (2) long gap, sensory; (3) short gap, motor; and (4) long gap, motor.


The primary outcome was MR, defined as greater than or equal to S3 and greater than or equal to M3 based on MRCC sensory scales and muscle strength grading (Table 2).16–19 In addition, higher-level MR was assessed and defined as greater than or equal to S3+ and greater than or equal to M4. Outcomes also included complications, consisting of revision surgery, symptomatic neuroma, pain, infection, or altered sensibility (paresthesia, cold intolerance, hyperesthesia). Donor-site complications (symptomatic neuroma or donor-site pain) were also evaluated in studies assessing autograft nerve repairs.

Table 2. - MRCC Sensory and Motor Function Scalea
Level of Recovery Sensory Motor
Not meaningful recovery S0 Absence of sensibility in the autonomous area M0 No contraction
Not meaningful recovery S1 Recovery of deep cutaneous pain sensibility within the autonomous area of the nerve M1 Flicker/trace contraction
Not meaningful recovery S2 Return of some degree of superficial cutaneous pain and tactile sensibility within the autonomous area of the nerve M2 Active movement with gravity eliminated
Meaningful recovery S3 Return of superficial cutaneous pain and tactile sensibility throughout the autonomous area, with disappearance of any pervious over response M3 Active movement against gravity
Higher level meaningful recovery S3+ Return of sensibility as in S3; in addition, there is some recovery of two-point discrimination within the autonomous area (7–15 mm) M4 Moderate movement against resistance
Higher level meaningful recovery S4 Complete recovery (two-point discrimination, 2–6 mm) M5 Normal/full power
aThe British Medical Research Council muscular function grading system includes M4-, slight movement against resistance; M4, moderate movement against resistance; and M4+, strong movement against resistance.

Statistical Analysis

Continuous variables were reported as averages and standard deviations, and categorical variables were reported as frequencies and percentages. Descriptive statistics with weighted averages were calculated for each cohort. The MR rate was compared between the nerve repair techniques along with comparison for each nerve injury category, using bootstrap methods.

A bootstrap using Monte Carlo methodology was performed to generate the distribution under the null hypothesis (MR outcomes of the two compared nerve repair techniques have the same distribution). This avoided type I error inflation attributable to underestimated standard error of the difference between studies.20,21 The P values between pooled data for repair techniques were obtained from comparison of the test statistic: the observed difference in MR rate reported per pooled data by nerve repair technique, with the distribution of the difference under the null hypothesis. A value of P < 0.05 was set as statistically significant for all tests. Forest plots for each repair modality (autograft, allograft, and conduit) were provided for each nerve type (sensory or motor) to demonstrate the mean MRCC, weight, and 95% confidence interval for each study and the pooled average for the study groups. Interstudy heterogeneity was qualified using the Q and I2 statistics, where less than 50% was considered low heterogeneity, 50% to 75% was considered moderate heterogeneity, greater than 75% was considered high heterogeneity, and Cochran Q test was applied for assessing the statistical significance. Statistical analyses were conducted using R version 3.5.2 (The R Foundation for Statistical Computing, Vienna, Austria).

Procedure Cost Analysis

The cost analysis was conducted for nerve graft repair using national Medicare hospital claims data for 2018, as reported in the Standard Analytic File. Autograft and allograft inpatient and outpatient nerve repairs were identified by International Classification of Diseases, 10th Revision, and CPT procedures codes, respectively. Hospital facility cost information was computed separately for inpatient and outpatient nerve repair cases across all gap lengths by applying national cost-to-charge ratios for hospital department charges calculated by the Centers for Medicare and Medicaid Services.


Included Studies

A total of 4143 studies were screened, and 115 studies were identified for review (Fig. 1). Thirty-five studies with a total of 1559 results (mixed nerve repairs had results for sensory and motor outcomes counted separately) were identified that reported MR, gap length, and type of nerve repaired. The analysis included 21 studies with 670 autograft repairs,22–42 nine studies with 711 allograft repairs,43–51 and seven studies with 178 conduit repairs43,44,52–56 (two studies evaluated more than one technique)43,44 (Table 3). Sixteen of these studies26,28–30,37,43,44,46–51,53,54,56 reported postoperative complications (Table 4). All studies reporting the full range of MRCC scores for subjects were presented in forest plots. [See Figure, Supplemental Digital Content 1, which shows forest plots displaying averaged MRCC score results for each clinical study captured in the analysis. Data are divided into five repair types. (Above) Autograft repair of sensory nerve gaps of 5 to 70 mm, (second from above) autograft repair of motor nerve gaps of 5 to 70 mm, (center) allograft repair of sensory nerve gaps of 5 to 70 mm, (second from below) allograft repair of motor nerve gaps of 5 to 70 mm, and (below) conduit-assisted repair of sensory nerve gaps of 5 to 30 mm. Diamonds represent averaged MRCC score subtotal for the five repair types. Edges of diamond represent 95% confidence interval for data. Squares are located at the mean MRCC score of each study. Sizes of squares are proportional to weight of clinical study, which is the number of patients, with the exception of the Ranger Registry clinical study in the allograft sensory plot, where the sample size was so large for this study that the weight was adjusted to fit on plot. For this study, the sample size was divided by 10. **Because of limited accessibility of data in the Leckenby 2019 clinical study, only MRCC scores for mixed or motor nerve injuries in lower limbs were considered in these plots, https://links.lww.com/PRS/F780.] The forest plots provide an overall representation of the data heterogeneity, the pooled mean, and 95% confidence interval.

Table 3. - Characteristics per Nerve Repair Technique
Total (%) Nerve Autograft (%) Nerve Allograft (%) Nerve Conduit (%)
Total no. of repairsa 1559 670 711 178
Nerve injury type
 Sensory 1216 (78.0) 411 (61.3) 627 (88.2) 178 (100.0)
  Short gap 835 (53.6) 245 (36.6) 412 (57.9) 178 (100.0)
  Long gap 381 (24.4) 166 (24.8) 215 (30.2)
 Motor 343 (22.0) 259 (38.7) 84 (11.8)
  Short gap 100 (6.4) 73 (10.9) 27 (3.8)
  Long gap 243 (15.6) 186 (27.8) 57 (8.0)
Location nerve repair
 Digital 834 (53.5) 271 (40.4) 397 (55.8) 166 (93.3)
 Arm 342 (21.9) 209 (31.2) 121 (17.0) 12 (6.7)
 Hand/arm combined 176 (11.3) 176 (26.3)
 Digit/hand/arm/leg combined 156 (10.0) 156 (21.9)
 Head and neck 31 (2.0) 31 (4.4)
 Lower extremity 20 (1.3) 14 (2.1) 6 (0.8)
No. of studies 35b 21 9 7
aSensory and motor results for mixed nerves counted as separate nerves.
bTwo studies evaluated more than one nerve technique. Not all mixed nerves reported motor and/or sensory data.

Table 4. - Complications Noted in Reviewed Literature
Complication Autograft Allograft Conduit
% No. of Studies/Total No. % No. of Studies/Total No. % No. of Studies/Total No.
Revision surgery NR NR/NR 5.96 3/498 6.16 5/146
Symptomatic neuroma NR NR/NR 3.00 1/475 NR NR/NR
Pain 20.59 2/34 19.44 2/36 37.50 2/40
Infection 3.57 1/28 0.94 7/666 4.55 4/88
Altered sensibility 13.33 1/15 33.33 1/18 25.88 3/85
Donor-site neuroma 14.29 1/28 NA NA/NA NA NA/NA
Donor-site pain 14.29 1/7 NA NA/NA NA NA/NA
NR, not reported; NA, not applicable.

Fig. 1.:
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram demonstrating the study screening and selection process.

Nerve Autograft

Twenty-one studies reported on nerve recovery following autograft nerve repair including four comparative studies23,26,30,33 and 17 case series22,24,25,27–29,31,32,34–42 (Table 5). Of the autograft repairs, 271 (40.4%) were in the digit, 209 (31.2%) were in the forearm/arm, 176 (26.3%) were in the hand/arm, and 14 (2.1%) were in the lower extremity (Table 3). The mechanisms of these injuries included, but were not limited to, laceration, blunt trauma, power tool injury, gunshot, and explosive blast. The donor nerves included the sural nerve, anterior/posterior interosseous nerve, lateral/medial antebrachial cutaneous nerve, or digital nerve. Postoperative complications noted in the autograft studies included pain in 20.59% of patients (two studies), infection in 3.57% of patients (one study), and altered sensibility in 13.33% of patients (one study). Revision and symptomatic neuroma rates were not reported in any of the autograft studies. Donor-site complications included donor-site neuromas in 14.29% of patients (one study) and donor-site pain in 14.29% of patients (one study) (Table 4). Patients in the autograft studies were predominantly men (77%), and the mean age was 31.5 years (range, 1 to 79 years). Overall MR for autograft was 71.8% for sensory function and 56% for motor function.

Table 5. - Autograft Clinical Studies
Reference Study Design No. of Results Nerve Location Nerve Types Included Gap Category Gap Length (mm) MINORS Score
Saeki et al., 2018 22 a Retrospective case series 37 Digit Sensory Short 18.7 15
Ahmad et al., 2017 23 Randomized comparative study 9 Arm Motor Short 27.4 12
Sallam et al., 2017 24 Retrospective case series 28 (56) sensory and motor MR results) Arm Mixed Long 30–50b 17
Unal et al., 2017 25 Case series 13 Digit Sensory Short 18.5 12
Flores, 2015 26 Retrospective comparative study 20 Arm Motor Long 57 17
Manoli et al., 2014 27 Retrospective case series 14 Digit Sensory Short 10–20b 10
Long 43.3
Chevrollier et al., 2014 28 Retrospective chart review 16 Digit Sensory Long 38 13
Pilanci et al., 2014 29 Case series 15 Digit Sensory Short 18.1 12
Stang et al., 2013 30 Retrospective comparative study 28 Digit Sensory Short 22 12
Bertelli et al., 2011 31 Prospective case series 5 (10 sensory and motor MR results) Arm Mixed Short 25 13
Long 40
Seidel et al., 2008 32 Retrospective case series 14 Lower extremity Mixed Short 25 8
Long 55.8
Roganovic et al., 2007 33 Prospective comparative study 23 Arm Motor Long 37 11
Amillo and Moro, 1999 34 Retrospective case series 6 Arm Motor Short 25 11
Long 68
Wang et al., 1996 35 a Case series 11 Digit Sensory Short 24 11
Vastamaki et al., 1993 36 Retrospective case series 42 Hand, arm Mixed Short <35b 12
Long 35–75b
Kallio et al., 1993 37 Retrospective case series 77 Digit Sensory Short 10–29b 12
Long 30–49b
Kallio et al., 1993 38 Prospective case series 67 (134 sensory and motor MR results) Hand, arm Mixed Short 20–39b 9
Long 40–69b
Doi et al., 1992 39 Randomized case series 18 (25 sensory and motor MR results) Arm Mixed Long 62.5 12
Digit Sensory Long 56.7
Barrios et al., 1990 40 Case series 33 (66 sensory and motor MR results) Arm Mixed Short 27.5 8
Long 51.8
Nunley et al., 1989 41 Retrospective case series 18 Digit Sensory Short 20.5 11
Long 33.6
Tenny and Lewis, 1984 42 Prospective case series 36 Digit Sensory Short 11.9 8
Long 36.3
MINORS, Methodological Index for Nonrandomized Studies.
aStudies not included in forest plots because of missing MRCC scores.
bGap length range; average gap length unavailable.

Nerve Allograft

The allograft repair studies included one randomized controlled trial43; a prospective case-control study47; six case series44,45,48–51; and an ambispective, multicenter registry study46 (Table 6). Of the allograft repairs, 397 (55.8%) were in the digit, 121 (17.0%) were in the forearm/arm, 156 (21.9%) were in the digit/hand/arm/lower extremities, 31 (4.4%) were in the head/neck, and six (0.8%) were in the lower extremity (Table 3). The mechanisms of these injuries included, but were not limited to, laceration, blunt trauma, power tool injury, amputation, avulsion, gunshot, shrapnel, explosive blast, neuroma resection, surgical transection, and oncologic resection. Postoperative complications noted in the allograft studies included revision surgery in 5.96% of patients (three studies), symptomatic neuromas in 3.0% of patients (one study), pain in 19.44% of patients (two studies), infection in 0.94% of patients (seven studies) infection, and altered sensibility in 33.33% of patients (one study) (Table 4). Patients in the allograft studies were predominantly men (78.2%) with a mean age of 41.5 years (range, 6 to 83 years). Overall MR rate for allograft was 81.9% for sensory function and 58.3% for motor function.

Table 6. - Allograft Clinical Studies
Reference Study Design No. of Nerve Repairs Nerve Location Nerve Types Included Gap Category Gap Length (mm) MINORS Score
Leckenby et al., 2020 45 Retrospective case series 156 Digit, hand, arm Sensory (n = 132) Short 15.1 11
Motor (n = 24) Long 36.3
Safa et al., 2020 50 Ambispective, multicenter 475 Digit, arm, face, lower Motor Long 45.5 13
Digit, arm, face, lower Motor Short 19.1
Digit, arm, face Sensory Long 38.4
Digit, arm, Face Sensory Short 14.
Rbia et al., 2019 44 Single-institution case reports and retrospective case series 18 Digit Sensory Short 18.4 17
Zuniga et al., 2017 47 Prospective, case-controlled, multisite study 18 Face Sensory Long 62.7 13
Means et al., 2016 43 Prospective, multicenter, randomized, double-blinded 6 Digit Sensory Short 12.8 20
Salomon et al., 2016 48 Retrospective, cohort 7 Face Sensory Long 50–70a 11
Guo et al., 2013 49 Retrospective case series 5 Digit Sensory Short 23 13
Taras et al., 2013 50 Prospective case series 18 Digit Sensory Short 11 12
Karabeckmez et al., 2009 51 Retrospective case series 8 Digit Sensory Short 22.3 14
MINORS, Methodological Index for Nonrandomized Studies.
aGap length range, average gap length unavailable.

Nerve Conduit

The seven studies on nerve conduit repairs included one randomized controlled trial43 and six case series44,52–56 (Table 7). Because commercially available conduits are indicated for use only in gaps up to 30 mm, all of the nerve injuries that were included in these studies were short gap, with 166 (93.3%) being repairs in the digit and 12 (6.7%) being in the arm (Table 3). Postoperative complications noted in the conduit studies included revision surgery in 6.16% of patients (five studies), pain in 37.5% of patients (two studies), infection in 4.55% of patients (four studies), and altered sensibility in 25.88% of patients (three studies) (Table 4). Symptomatic neuromas were not reported in any of the conduit studies. Patients in the conduit studies were also predominantly men (78.6%), and the mean age was 41.2 years (range, 11 to 83 years). Overall MR for the conduit group was 62.2% for sensory function. No studies reported on mixed or motor nerve repairs with conduits.

Table 7. - Conduit Clinical Studies
Reference Study Design No. of Nerve Repairs Nerve Location Nerve Types Included Gap Category Gap Length (mm) MINORS Score
Rbia et al., 2019 44 Single-institution case reports and retrospective case series 19 Digit Sensory Short 14 17
Means et al., 2016 43 Prospective, multicenter, randomized, double-blinded 12 Digit Sensory Short 12.2 20
Lohmeyer et al., 2014 52 a Prospective cohort study 40 Digit Sensory Short 12.3 11
Haug et al., 2013 53 a Case series 45 Digit Sensory Short 12 12
Chiriac et al., 2012 54 Case series 28 Digit Sensory Short 10.8 13
Arm Sensory Short 11.3 13
Taras et al., 2011 55 Prospective case series 22 Digit Sensory Short 12 13
Lohmeyer et al., 2009 56 Prospective cohort study 12 Digit Sensory Short 12.7 11
MINORS, Methodological Index for Nonrandomized Studies.
aStudies not included in forest plots because of missing MRCC scores.

Meaningful Recovery Comparisons by Gap Size and Nerve Type

Overall MR for both sensory and motor function was not significantly different between autograft (n = 670) and allograft (n = 711) (sensory, 71.8% versus 81.9%, P = 0.186; motor, 56.0% versus 58.3%, P = 0.500). However, meaningful sensory recovery rates for both autograft and allograft were significantly better than for conduit, which had a meaningful sensory recovery rate of 62.2% (n = 178; P = 0.031 and P = 0.033, respectively) (Fig. 2). In addition, MR rates for autograft and allograft remained comparable across short and long gaps for sensory and motor function [short gap sensory autograft (n = 245) versus allograft (n = 412), 81.6% versus 87.1%, P = 0.186; long gap sensory autograft (n = 166) versus allograft (n = 215), 57.2% versus 72.6%, P = 0.055; short gap motor autograft (n = 73) versus allograft (n = 27), 69.9% versus 70.4%, P = 0.500; long gap motor autograft (n = 186) versus allograft (n = 57), 50.5% versus 52.6%, P = 0.425] (Fig. 3).

Fig. 2.:
Overall meaningful sensory recovery by repair type. Overall meaningful sensory recovery, defined as MRCC greater than or equal to S3, was not significantly different between autograft and allograft. However, both autograft and allograft meaningful sensory recovery were significantly better than that for conduit (P = 0.031 and P = 0.033, respectively).
Fig. 3.:
MR by gap size and nerve type. There were no significant differences in MR between autograft and allograft across both short and long gaps for both sensory and motor function.

Although greater than or equal to S3/M3 on the MRCC scale has historically been the threshold recognized as clinically meaningful, rates of a higher threshold of recovery (defined as ≥S3+/M4 on the MRCC scale) were also assessed. Overall MR rates at the higher threshold for autograft were 52.6% for sensory and 36.3% for motor. For allograft, overall rates were 66.7% for sensory and 36.7% for motor. When evaluated by gap length and nerve type, the autograft and allograft groups were again comparable (short gap sensory, 67.8% versus 75.0%, P = 0.284; long gap sensory, 30.1% versus 47.7%, P = 0.117; short gap motor, 39.7% versus 42.9%, P = 0.400; and long gap motor, 34.9% versus 33.3%, P = 0.542) (Fig. 4).

Fig. 4.:
Higher threshold MR by gap size and nerve type. There were no significant differences in higher threshold MR between autograft and allograft across both short and long gaps for both sensory and motor function.

MR rates were also analyzed by publication date, because 43% of the autograft studies were published before 2000 and 89% of the allograft studies were published after 2010 (Fig. 5, above). The MR rates for autograft by decade were consistent (68.2% versus 70.3% versus 71.4%, respectively) (Fig. 5, below), indicating that surgical technique advancements likely did not have an impact on autograft MR rates, and therefore did not affect the comparison of autograft to allograft in this analysis.

Fig. 5.:
Historical analysis of publications. (Above) Number of studies published per decade by repair type. Forty-three percent of included autograft studies were published before 2000 and 0% of allograft or conduit studies were published then. (Below) MR per decade by repair type. MR for autograft is consistent over the decades, indicating that evolution of technique over this time period did not impact MR rates.

Cost Analysis

As there were no significant differences in the MR rates between autograft and allograft, a cost analysis to determine whether there were cost differences by repair type was performed. Conduits were not included in this analysis because conduit delivered significantly lower MR than autograft and allograft in short gap sensory nerve injuries and were not applicable in the other injury types. Evaluation of the data from the 2018 Standard Analytic File reported 340 hospital nerve graft repair claims, where 293 were outpatient and 47 were inpatient. A total of 25 inpatient autograft, 22 inpatient allograft, 95 outpatient autograft, and 198 outpatient allograft procedures were evaluated. Total inpatient costs for allograft repair were less than autograft, $25,751 and $29,560, respectively (Fig. 6, left). Total outpatient costs were similar for allograft and autograft, $13,143 and $12,635, respectively (Fig. 6, right). The higher inpatient costs for autograft appear to be attributable to operating room costs ($13,227 versus $9742 for allograft). In the outpatient setting, the operating room costs are also higher for autograft ($5352 versus $3717), but this is offset by the higher implant cost for allograft ($5623 versus $2187 for autograft).

Fig. 6.:
Economic analysis for autograft and allograft. Evaluation of the 2018 Standard Analytic File showed that total costs for allograft repair were less than costs for autograft in the inpatient setting (left) and were similar for allograft and autograft in the outpatient setting (right).


This systematic literature review of 35 studies reporting 1559 nerve repair outcomes included 670 autograft repairs, 711 allograft repairs, and 178 conduit repairs. This analysis showed that the MR rates for autograft and allograft repairs of sensory, motor, or mixed motor nerve repairs showed no significant differences. The similarities noted between the motor and mixed motor nerve repairs were unexpected, as historically the standard of care for bridging nerve defects is autograft. Autografts have been considered the standard for bridging nerve gaps because they offer an axonal guidance scaffold through intact endoneurial tubes and are nonimmunogenic.57 However, recent literature suggests that in mixed and motor nerve repairs, autograft and allograft repairs were comparable.46,58 Furthermore, results also showed that autograft and allograft repairs had significantly higher MR rates as compared with conduit repairs. These comparisons were analyzed in short gap (>5 to ≤30 mm) sensory nerve injuries, which was the only category where conduit data were available (81.6% and 87.1%, respectively, versus 62.2%). These results were expected and comparable to a nerve allograft versus conduit study performed by Means et al., which showed that patients with digital nerve gaps repaired with nerve allografts showed more consistent functional sensory outcomes compared with conduits.43 Furthermore, the reported pain rates for conduit as compared with autograft and allograft was 37.5% versus 20.59% and 19.44%, respectively, suggesting that repair with autograft or allograft may improve outcomes with lower complication rates compared with conduit in short gap sensory nerve repairs.

Before the advent of alternative peripheral nerve gap treatments, the historical standard for repair of nerve gap injuries where a tension-free coaptation was not possible was autograft. This study suggests that autograft and allograft results showed comparable outcomes regardless of gap length or nerve type (sensory, 71.8% versus 81.9%; motor, 56.0% versus 58.3%). Furthermore, the complication rates for autograft and allograft were comparable, and with regard to infection, both were in line with the expected surgical rate. Therefore, the tradeoffs between autograft and allograft repairs are worth further consideration.

When evaluating these tradeoffs, it is important to consider autograft donor-site complications and the index procedure costs. Allograft has been noted to eliminate donor-site complications and have reduced operating time.59,60 One study in this analysis reported that 14.3% of patients experienced donor-site neuroma and associated pain.30 Although these data are limited, symptomatic neuromas reduce patient quality of life, increase the risk of developing an opioid misuse disorder, may lead to multiple additional operations, and lead to donor-site allodynia and other complications such as infection.59,61–67 Finally, the procedure cost analysis demonstrated that overall allograft costs are lower than autograft costs in the inpatient setting and comparable in the outpatient setting. This suggests that allograft repair may achieve similar outcomes at similar or lower costs as compared with autograft repair.

Systematic reviews by their nature have some limitations. This analysis included data from studies with various injury types, study designs, populations, study n values, gap lengths, nerve locations, patient follow-up, and disclosed industry funding. Furthermore, studies including mixed motor nerves typically showed limited n values. In addition, no studies compared all reconstructive techniques using a randomized study design. Therefore, a pooled analysis was performed, which did not account for study population differences. In addition, generalization was difficult, as repair techniques offered variable repair numbers and nature of injury. In addition, all surgical treatment groups were not applicable across all gaps and nerve types, as analysis of conduit repairs were limited to only short gap sensory nerve injuries and it is unknown whether follow-up was adequate in the studies, as the distance from the injury to the distal target was not assessed. Lastly, as expected, authors reported industry grant funding of their research in four of nine allograft repair studies43,46,48,50 and in one of seven nerve conduit studies.55 Although the variability introduced because of these limitations should be considered, it is important to note that this analysis offers valuable insight into autograft, allograft, and conduit repair outcomes, complications, and costs that could not be analyzed by limiting this analysis to a specific nerve injury type, gap length, or study design.


Autograft and allograft have MR rates that do not differ significantly regardless of gap length or nerve type and are significantly better than the MR rates reported for conduits in short gap sensory nerves, the only modality in which conduits were used. In addition, the cost analysis performed demonstrates that allograft does not represent an increased economic burden compared with autograft. Further direct comparative clinical studies would be beneficial to confirm these findings and offer additional support.


Drs. Eberlin, Evans, Mercer, Greenberg, and Styron are paid consultants of Axogen Corporation, a producer of peripheral nerve repair technologies discussed in this review. However, the authors of the article had complete and final control of the data collection, analysis, and manuscript composition. Dr. Lans has no financial interests to declare.


This research was financially supported by a grant from Axogen Corporation.


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