The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 94, Issue 22

Scientific Articles | November 21, 2012

The Effect of Collagen Nerve Conduits Filled with Collagen-Glycosaminoglycan Matrix on Peripheral Motor Nerve Regeneration in a Rat Model

Joo-Yup Lee, MD, PhD¹; Guilherme Giusti, MD²; Patricia F. Friedrich, AAS²; Simon J. Archibald, PhD³; John E. Kemnitzer, PhD³; Jignesh Patel, BS, MS³; Namrata Desai, BS, MS³; Allen T. Bishop, MD²; Alexander Y. Shin, MD²

¹ Department of Orthopedic Surgery, St. Vincent’s Hospital, The Catholic University of Korea, 93 Ji-dong, Paldal-gu, Suwon 442-723, South Korea. E-mail address: jylos1@gmail.com
² Microvascular Research Laboratory (G.G. and P.F.F.) and Department of Orthopedic Surgery (A.T.B. and A.Y.S.), Mayo Clinic, 200 First Street S.W., Rochester, MN 55905. E-mail address for G. Giusti: guigiusti@hotmail.com. E-mail address for P.F. Friedrich: friedrich.patricia@mayo.edu. E-mail address for A.T. Bishop: bishop.allen@mayo.edu. E-mail address for A.Y. Shin: shin.alexander@mayo.edu
³ Integra LifeSciences Corporation, 103 Morgan Lane, Plainsboro, NJ 08536. E-mail address for S.J. Archibald: simon.archibald@integralife.com. E-mail address for J.E. Kemnitzer: john.kemnitzer@integralife.com. E-mail address for J. Patel: jignesh.patel@integralife.com. E-mail address for. N. Desai: namrata.desai@integralife.com

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Investigation performed at the Microvascular Research Laboratory, Mayo Clinic, Rochester, Minnesota

J Bone Joint Surg Am, 2012 Nov 21;94(22):2084-2091. doi: 10.2106/JBJS.K.00658

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Abstract

Background:

Bioabsorbable unfilled synthetic nerve conduits have been used in the reconstruction of small segmental nerve defects with variable results, especially in motor nerves. We hypothesized that providing a synthetic mimic of the Schwann cell basal lamina in the form of a collagen-glycosaminoglycan (GAG) matrix would improve the bridging of the nerve gap and functional motor recovery.

Methods:

A unilateral 10-mm sciatic nerve defect was created in eighty-eight male Lewis rats. Animals were randomly divided into four experimental groups: repair with reversed autograft, reconstruction with collagen nerve conduit (1.5-mm NeuraGen, Integra LifeSciences), reconstruction with collagen nerve conduit filled with collagen matrix, and reconstruction with collagen nerve conduit filled with collagen-GAG (chondroitin-6-sulfate) matrix. Nerve regeneration was evaluated at twelve weeks on the basis of the compound muscle action potential, maximum isometric tetanic force, and wet muscle weight of the tibialis anterior muscle, the ankle contracture angle, and nerve histomorphometry.

Results:

The use of autograft resulted in significantly better motor recovery compared with the other experimental methods. Conduit filled with collagen-GAG matrix demonstrated superior results compared with empty conduit or conduit filled with collagen matrix with respect to all experimental parameters. Axon counts in the conduit filled with collagen-GAG matrix were not significantly different from those in the reversed autograft at twelve weeks after repair.

Conclusions:

The addition of the synthetic collagen basal-lamina matrix with chondroitin-6-sulfate into the lumen of an entubulation repair significantly improved bridging of the nerve gap and functional motor recovery in a rat model.

Clinical Relevance:

Use of a nerve conduit filled with collagen-GAG matrix to bridge a motor or mixed nerve defect may result in superior functional motor recovery compared with commercially available empty collagen conduit. However, nerve autograft remains the gold standard for reconstruction of a segmental motor nerve defect.

Figures in this Article

Introduction

Introduction | Materials and Methods | Results | Discussion

Since the introduction of the concept of nerve entubulation by Lundborg and Hansson¹, bioabsorbable nerve conduits have been commonly applied to bridge short (<2-cm) segmental nerve defects. Although there are many potential advantages of using nerve conduit, the indications are generally limited to the digital sensory nerves, and the outcomes of repair with nerve conduit to date remain inferior to those of the gold standard, use of nerve autograft². To expand the clinical application of nerve conduit to the repair of larger mixed or motor nerve defects and to improve the outcome, many investigations have focused on improving the hollow nerve conduit³.

Collagen-glycosaminoglycan (GAG) matrices have been developed as analogs of the extracellular matrix, and these are currently being used for skin regeneration in patients with massive, full-thickness skin loss^4-6. As wound-healing processes in nerves are similar to those in skin⁷, application of collagen-GAG matrix for peripheral nerve regeneration would be ideal. Previous studies have shown that use of collagen or silicone tubes filled with collagen-GAG matrix across a 10-mm gap in the rat sciatic nerve resulted in enhanced structural and electrophysiological properties, with results comparable with those resulting from use of autograft^8,9.

As functional recovery does not necessarily correlate with electrophysiology and nerve histomorphometry results¹⁰, it is unknown whether use of a conduit filled with collagen-GAG matrix would improve functional motor recovery compared with use of a hollow conduit. Isometric tetanic muscle force measurement is a direct measure of effective recovery of an individual muscle after reinnervation, and this technique has been used successfully to demonstrate the difference in peroneal motor nerve recovery after use of various commercially available hollow nerve conduits¹¹.

The purposes of this study were (1) to determine the effect of collagen conduit filled with collagen-GAG matrix on functional motor nerve recovery as measured by isometric tetanic force in a rat sciatic nerve defect model, and (2) to determine the effect of the GAG component in conduit filled with collagen-GAG matrix on the histological morphology of the regenerated nerve bridge between the proximal and distal stumps of the nerve defect.

Materials and Methods

Introduction | Materials and Methods | Results | Discussion

This study was approved by our Institutional Animal Care and Use Committee. A unilateral 10-mm sciatic nerve defect model was created in male Lewis rats weighing 250 to 300 g. Eighty-eight rats were randomly divided into four experimental groups: group I underwent repair with a bridging autograft by reversing the excised nerve segment, group II underwent reconstruction with an empty collagen conduit (1.5-mm NeuraGen; Integra LifeSciences, Plainsboro, New Jersey), group III underwent reconstruction with a conduit filled with collagen matrix without GAG, and group IV underwent reconstruction with a conduit filled with collagen-GAG matrix. After twelve weeks, nerve regeneration was evaluated with use of the compound muscle action potential (CMAP), maximum isometric tetanic force, and wet muscle weight of the tibialis anterior muscle; the ankle contracture angle; and nerve histomorphometry. Although the value at twelve weeks may not reflect the ultimate motor strength that would be achieved with a longer duration of follow-up, it was expected to allow detection of differences between groups in isometric tetanic force measurement, histology, and nerve histomorphometry.

Fabrication of Collagen Conduits and Collagen-GAG Matrices

The collagen conduits were fabricated from highly purified type-I collagen derived from bovine deep flexor tendon and cross-linked by gaseous formaldehyde treatment¹². The conduits had an inner diameter of 1.5 mm and were made of collagen layers arranged in a loosely packed laminar fashion⁹. The cross-linking treatment of the collagen conduit was modified to facilitate early degradation that would promote nerve regeneration¹³. The collagen-GAG matrix was prepared according to a process similar to that of Yannas et al.⁵. To prepare the matrix, a collagen and chondroitin-6-sulfate proteoglycan suspension was dispensed into the collagen conduits. The filled conduits were frozen under controlled conditions and then lyophilized to produce a highly porous matrix with an axially oriented pore structure (Fig. 1). The conduits for group IV contained collagen-GAG matrix, and the conduits for group III contained only type-I collagen matrix without a GAG component. The implants were sterilized with ethylene oxide and supplied ready for use.

Fig. 1

Transverse (A) and longitudinal (B) sections of the conduit filled with collagen-glycosaminoglycan (GAG) matrix viewed by scanning electron microscopy (SEM). The pore channels in the collagen-GAG matrix are axially aligned to mimic the Schwann cell basal lamina as a mechanism to effectively support bridging across a critical-sized nerve defect. The bar is 0.5 mm long.

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Surgical Procedures

The sciatic nerve on the experimental side of the anesthetized rat was fully exposed from the inferior margin of the piriformis muscle to a point 5 mm distal to the bifurcation of the peroneal and distal tibial branches of the nerve. A 10-mm segment of the sciatic nerve was excised with sharp microsurgical scissors under an operating microscope. The mean length of the rat sciatic nerve from the sciatic notch to the bifurcation point has been reported to be 19.8 mm (range, 15 to 23 mm; standard error of the mean, 2.8 mm)¹⁴. The resected segment of 10 mm thus represents approximately 50% of the whole sciatic nerve in the rat. In group I, the excised sciatic nerve segment was reversed and repaired between the proximal and distal stumps using 10-0 nylon epineural interrupted sutures. In group II, a 12-mm empty collagen nerve conduit was used to bridge the gap; two 8-0 nylon epineural sutures were used to keep the nerve ends 1 mm inside the conduit at each side. In groups III and IV, a conduit filled with collagen matrix with or without GAG was used to bridge the nerve defect. The conduit was cut to a 12-mm length before soaking, and the matrix filling at both ends of the conduit was gently removed with jeweler’s forceps to create an atrium approximately 1 mm in length into which each nerve stump could be inserted. Bridging of the defect was performed with the same technique used in group II.

Compound Muscle Action Potential

The sciatic nerve was exposed through a previously made lateral skin incision. A miniature bipolar stimulating electrode (Harvard Apparatus, Holliston, Massachusetts) was clamped around the exposed sciatic nerve. Two recording electrodes were placed through the skin onto the tibialis anterior muscle surface. The CMAP in the tibialis anterior muscle was measured with a VikingQuest portable electromyography (EMG) system (CareFusion, San Diego, California). The stimulation duration was 0.02 ms, and the intensity was the minimum necessary to elicit a maximal CMAP signal. The responses were analyzed on the basis of the CMAP amplitude. The same evaluations were performed for the contralateral side, and the CMAP results were normalized using the data from the contralateral side.

Maximum Isometric Tetanic Force and Wet Muscle Weight

The maximum isometric tetanic muscle force was measured as previously described¹⁵. After the CMAP study, the incision was extended distally to access the peroneal nerve distal to the graft, and another skin incision was made anterior to the ankle to expose the tibialis anterior tendon. The tibialis anterior tendon was transected distally, protecting its innervation and blood supply. The knee and ankle joints were immobilized to a platform with Kirschner wires, and the tibialis anterior tendon was connected to a force transducer (MDB-50; Transducer Techniques, Temecula, California) using a custom clamp. The same miniature bipolar stimulating electrode used for CMAP measurement was placed around the peroneal nerve distal to the repair site. A bipolar stimulator (SD9; Grass Instrument Company, Quincy, Massachusetts) was used to generate the stimulus, and the signal acquired from the force transducer was processed on a computer with use of LabVIEW software (National Instruments, Austin, Texas). All contractions were generated at supramaximal voltage to ensure maximal activation of all tibialis anterior motor units. The highest force plateau of the force-frequency curve was defined as the maximum isometric tetanic force. At the end of the procedure, the tibialis anterior muscle was carefully dissected off the surrounding tissues and weighed (in grams) after removal of the tendon. The same evaluations were performed for the contralateral side, and the muscle force and weight were normalized using the data from the contralateral side.

Ankle Contracture Angle

The degree of ankle contracture was also used to compare the outcomes of the different methods of repairing the sciatic nerve defect¹⁶. The ankle contracture angle was measured between the lines representing the anterior aspect of the tibia and the dorsal aspect of the foot with the ankle in maximal passive plantar flexion.

Nerve Histology and Morphometric Analysis

The sciatic nerve and any accompanying conduit were exposed, and in situ fixation was performed for five minutes using 2% Trump fixative. Four segments of the regenerated nerve were harvested, two from the midportion of the graft and one each from the proximal and the distal repair site. Tissue segments from the proximal repair site, midportion of the graft, and distal repair site were embedded in paraffin and cut into either a cross-section or a longitudinal section. The sections were stained with Masson trichrome to evaluate the changes in the collagen conduits and the nerve growth patterns in the conduits.

Another segment from the midportion of the graft was postfixed in 1% osmium tetroxide and embedded in epoxy resin. The nerve tissue sample was cut into 1-μm-thick sections and stained with toluidine blue. The nerve sections were digitized for image analysis using a video camera connected to a light microscope. Histomorphometric analysis was performed with use of Image-Pro software (Image-Pro Plus version 7.0; Media Cybernetics, Bethesda, Maryland). Low-magnification (×40) images were used to measure the total area of the regenerated nerve. Fields in the high-magnification (×400) images were randomly selected and morphometric measurements were obtained. This was repeated twice to decrease the selection bias, and the results were averaged. The selected morphometric parameters were the total number of axons, the myelinated fiber area, the N ratio, and the nerve fiber density. The number of axons in each high-magnification image was counted, and the calculated nerve fiber density was multiplied by the total tissue cable area to obtain the total number of axons. The myelin area was determined by manually selecting the dark area of the field, and this area was added to the axon area to calculate the myelinated fiber area. The N ratio was calculated by dividing the total myelinated fiber area by the total tissue cable area. The N ratio represents the total mass of the regenerating nerve in the conduit, and it provides information regarding the number of sprouting events¹⁷.

Statistical Analysis

The number of rats required in each group had been determined on the basis of the results of isometric tetanic muscle force tests obtained during a previous study¹⁵. It was estimated that seventeen rats in each group would provide 80% power to detect a 10% difference in mean muscle force between the groups (standard deviation = 10 g; α = 0.05, two-sided). In order to guard against potential attrition, the sample size was increased to twenty-two in each group. Maximum isometric tetanic force was selected as the primary outcome measurement. One-way analysis of variance (ANOVA) corrected by a Bonferroni post-hoc test was used to assess the statistical differences between groups. All results were reported as the mean and the standard deviation, and the level of significance was set at α ≤ 0.05.

Source of Funding

This study was supported by a research grant from Integra LifeSciences Corporation. Some of the authors are employees of Integra LifeSciences, and all of the conduits were donated by Integra LifeSciences.

Results

Introduction | Materials and Methods | Results | Discussion

Six of the eighty-eight rats died as a result of anesthesia complications. The repair sites in one rat each from groups I, III, and IV pulled out, and the data from these rats were excluded from the analysis. In total, twenty rats in group I, nineteen in group II, twenty in group III, and twenty in group IV were therefore available for analysis (Fig. 2). Complications such as postoperative wound dehiscence or infection were not observed. Almost complete resorption of the conduits was frequently observed in groups III and IV; the conduits in group II were still present at twelve weeks.

Fig. 2

Compound muscle action potential (CMAP), isometric tetanic force, and muscle weight of the tibialis anterior and ankle contracture angle for the four test groups. GAG = glycosaminoglycan. The asterisks indicate significant differences (p < 0.05).

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Compound Muscle Action Potential

The mean normalized CMAP amplitude (and standard deviation) was 49.7% ± 7.7% for group I, 26.6% ± 6.9% for group II, 32.4% ± 7.6% for group III, and 39.8% ± 8.8% for group IV. The CMAP amplitude in group I was significantly greater than that in the other experimental groups (p < 0.001 compared with groups II and III, and p = 0.001 compared with group IV). Group IV had a better result than group II (p < 0.001) and group III (p = 0.023).

Maximum Isometric Tetanic Force

The normalized mean maximum isometric tetanic force was 46.1% ± 7.9% in group I, 22.1% ± 8.6% in group II, 28.9% ± 8.6% in group III, and 37.5% ± 9.9% in group IV. Group I showed significantly better motor recovery than the other experimental groups (p < 0.001 compared with group II, p < 0.001 compared with group III, and p = 0.017 compared with group IV). Group IV had a better result than group II (p < 0.001) and group III (p = 0.017).

Wet Muscle Weight

The normalized mean wet muscle weight of the tibialis anterior muscle was 62.0% ± 7.9% in group I, 40.4% ± 8.1% in group II, 46.1% ± 7.8% in group III, and 53.6% ± 6.6% in group IV. The mean weight was significantly greater in group I than in the other experimental groups (p < 0.001 compared with groups II and III, and p = 0.004 compared with group IV). The results in group IV were better than those in group II (p < 0.001) and group III (p = 0.017).

Ankle Contracture Angle

The ankle contracture angle was 133.5° ± 7.8° in group I, 97.2° ± 8.0° in group II, 103.3° ± 9.2° in group III, and 115.9° ± 7.9° in group IV. The angle was significantly greater in group I than in the other experimental groups (p < 0.001 for all). The result in group IV was better than those in groups II and III (p < 0.001 for both).

Nerve Histology

Longitudinal sections of the proximal segment showed a clear distinction between group II and group IV. In group II, the end of the conduit was not absorbed, and the regenerated nerve was less dense compared with the proximal stump. In contrast, in group IV, the conduit was absorbed and this had allowed the proximal stump to regenerate smoothly. The regenerated nerve in group IV was denser than that in group II (Fig. 3). In cross-sections of the middle segments, the conduits in groups III and IV were smaller in size than those in group II. The endoneurial contents of myelinated axons and cell bodies were denser and more uniformly distributed in group IV than in group II or group III (Fig. 4).

Fig. 3

Histological findings at the proximal nerve repair site for groups II and IV (Masson trichrome, ×40). The end of the empty conduit used in group II was not absorbed, and the regenerated nerve was less dense compared with the proximal stump. The conduit with collagen-GAG matrix used in group IV was absorbed and allowed the proximal stump to regenerate smoothly.

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Fig. 4

Histological findings of the mid-graft transverse section for the four groups (Masson trichrome, ×40). The conduits in groups III and IV were decreased in size compared with those in group II. The regenerated nerve in the mid-graft was more compact in group IV than in groups II and III. The bar is 0.5 mm long.

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Morphometric Analysis

The total number of axons was 13,216 ± 2496 in group I, 5568 ± 1572 in group II, 8144 ± 2885 in group III, and 11,303 ± 2755 in group IV. Although group I had more axons than group II and group III (p < 0.001 for both), there was no significant difference in the total axon population between group I and group IV (p = 0.105). The myelinated fiber area was 31.1 ± 3.9 μm² in group I, 10.3 ± 2.7 μm² in group II, 16.8 ± 5.2 μm² in group III, and 24.2 ± 5.6 μm² in group IV. All differences between groups were significant (p < 0.001). The N ratio was 0.44 ± 0.05 in group I, 0.10 ± 0.03 in group II, 0.24 ± 0.07 in group III, and 0.34 ± 0.08 in group IV. All differences between groups were significant (p < 0.001). The nerve fiber density was 20,693 ± 3908 axons/mm² in group I, 4903 ± 1384 axons/mm² in group II, 14,343 ± 5081 axons/mm² in group III, and 19,908 ± 4852 axons/mm² in group IV. Group I had greater nerve fiber density than group II and group III (p < 0.001 for both), but no difference was found between group I and group IV (p = 1.000) (Fig. 5). Group IV had significantly more axons than group II (p < 0.001) and group III (p = 0.002). Group IV had greater nerve fiber density than group II and group III (p < 0.001 for both).

Fig. 5

Histological findings of the mid-graft transverse sections for the four groups (toluidine blue, ×40). The regenerated axons were more dense and organized in the autograft (group I) and in the conduit with collagen-GAG matrix (group IV) compared with the empty conduit or conduit with collagen matrix (groups II and III).

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Discussion

Introduction | Materials and Methods | Results | Discussion

Bioabsorbable nerve conduit is potentially effective in aiding motor nerve regeneration, but clinical studies on motor nerve repair with use of synthetic conduits are limited in number and most are limited in sample size, which has so far precluded wide acceptance of its use in bridging motor or mixed nerve defects^18,19. To be used in the repair of motor or mixed nerve defects, the nerve conduits should be improved and their effect on motor recovery should be proven in animal studies. Few animal studies comparing nerve conduits have focused on evaluating the recovery of muscle function^20,21.

In this study using a critical-sized nerve defect model, we demonstrated that the conduit filled with collagen-GAG matrix was more effective than an empty conduit or a conduit filled with collagen matrix in terms of functional motor recovery, although it remained inferior to nerve autograft. Collagen-GAG matrix has been developed as an analog of the Schwann cell extracellular matrix, and its use as an internal framework in the nerve conduit to facilitate axonal growth has been investigated previously^6,8,9. Collagen is the major structural protein in humans and it has been utilized in the biomedical field because of its low antigenicity, its biodegradability, and its good mechanical properties^22,23. Addition of GAG to collagen matrix modulates growth factors and cytokines by its involvement in adhesion, migration, proliferation, and differentiation of cells^24,25. The three-dimensional structure of the collagen-GAG matrix influences cell migration behavior and collagen and growth factor production from fibroblasts^26,27. Since the collagen-GAG matrix is axially aligned, Schwann cells can migrate along the linear paths and form long, linear columns to support axon elongation and myelination²⁸.

We found that conduits containing collagen matrix with or without GAG were absorbed earlier than empty collagen conduits. It is well known that degradable conduits induce a higher quality of regeneration compared with nondegradable conduits^17,29. Harley et al.¹³ studied the optimal degradation rate of collagen conduits used for regeneration of the rat sciatic nerve and found that the maximal quality of regeneration corresponded to a degradation rate with a half-life of approximately three weeks following implantation. Ellis and Yannas³⁰ demonstrated that long-term electrophysiological results were significantly better for the rapidly degrading collagen-GAG matrices. However, the degradation rate of regenerative matrices should appropriately match the rate of tissue regeneration since premature collapse of the implant could adversely affect tissue regeneration⁶. This complication was reported in polyglycolic acid nerve conduits¹¹.

The cross-sectional diameters of the matrix-filled conduits were reduced. One possible explanation for this effect is related to myofibroblast function. The transected peripheral nerve is subject to wound-healing processes largely similar to those observed in skin⁷. Myofibroblasts have also been identified in the regenerating peripheral nerve after six weeks³¹. The function of the axially aligned myofibroblasts is not fully understood. Axially aligned myofibroblasts may facilitate nerve regeneration by shortening the nerve gap³². These cells may be responsible for aligning newly synthesized collagen fibers and possibly regenerated axons during the healing process³¹. Since circumferential contractile forces could cause the constriction of the stump and the regenerating nerve³³, it is hypothesized that two competing forces should be balanced to regenerate the nerve across a tube. The presence of collagen-GAG matrix may promote early axonal elongation within the gap prior to confluence of the contractile tissue capsule³⁴.

Although nerve histomorphometry does not necessarily correlate with functional recovery¹⁰, the results from the morphometric analysis showed similar trends to those from the functional evaluation. The use of conduit filled with collagen-GAG matrix significantly increased every morphometric parameter compared with use of empty conduit or conduit filled with collagen matrix. The number of axons and the nerve fiber density obtained from conduit with collagen-GAG matrix were comparable with those from autograft. These results are corroborated by other studies^8,9. However, the myelinated fiber area and the N ratio, which are influenced by the degree of myelination, were inferior compared with those from autograft. This might explain the inferior functional results, such as compound muscle action potential and isometric tetanic force measurement, in conduits with collagen-GAG matrix compared with autograft.

We found that the GAG component of the collagen-GAG matrix played an important role in peripheral nerve regeneration. It is unclear why the GAG in the collagen-GAG matrix acts differently than the GAGs in the central nervous system. One possible explanation is that GAGs are heterogeneous in nature and the GAG composition varies among anatomic locations. The peripheral nerve is a distinctly different environment than the central nervous system, and it has an innate regenerative capacity that the central nervous system lacks almost entirely. Another study has demonstrated that the nerve gap can be effectively bridged by Schwann cells, fibroblasts, and blood vessels in the complete absence of axons, reestablishing the histological architecture of the peripheral nerve³⁵. Therefore, the collagen-GAG matrix may be acting as a preferential substrate not for axons but for Schwann cells migrating into the deficit from both the proximal and distal nerve stumps. The Schwann cells then provide a living and supporting pathway for axon regeneration in the same way that they do through the distal pathway following nerve transection and repair. Chondroitin-6-sulfate proteoglycan is present in the normal Schwann cell basal lamina, and its expression is upregulated by Schwann cells following nerve injury and plays an important role in Schwann cell migration³⁶.

The relative relationships among the experimental groups were remarkably consistent across all of the parameters tested. Autograft showed the best results compared with all other experimental groups, and conduit filled with the collagen-GAG matrix showed superior results compared with the empty conduit and the conduit with collagen matrix. This study is limited by the single end point of twelve weeks, which may not have been long enough to evaluate motor recovery in a sciatic nerve defect model. However, we believe that it is long enough to show the difference in the early functional motor recovery among groups, as was demonstrated in our previous study¹¹. Acellular nerve allograft, which is currently clinically available, could also be assessed using similar measurements. The proprietary nature of the commercially available acellular nerve allograft prevented its direct comparison in this study.

In conclusion, autologous nerve grafting remains the gold standard in the reconstruction of critical-sized segmental motor nerve defects. However, the conduit filled with collagen-GAG matrix gave superior results with respect to isometric tetanic force generation compared with empty conduit or conduit filled with collagen matrix in this rat sciatic nerve model. The potential benefit of synthetic bioabsorbable conduit would include an unlimited supply that could be provided in a variety of lengths, diameters, and configurations; avoidance of complications of allograft tissue transplantation; elimination of donor site morbidity; and the ability to bridge short nerve motor nerve deficits in all peripheral nerve injuries. We believe that the first clinical trial for collagen-GAG matrix conduit may have been to bridge a small median nerve defect (<2 cm) about the wrist³⁷. However, further investigation of the effects of greater defect length and diameter and comparison with commercially available acellular nerve grafts in a larger animal study will be required prior to translation to human use.

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Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, one or more of the authors has had another relationship, or has engaged in another activity, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Topics

conduit implant ; collagen ; glycosaminoglycans ; neurons ; motor nerve

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Joo-Yup Lee, Guilherme Giusti, Patricia F. Friedrich, Simon J. Archibald, John E. Kemnitzer, Jignesh Patel, Namrata Desai, Allen T. Bishop, Alexander Y. Shin; The Effect of Collagen Nerve Conduits Filled with Collagen-Glycosaminoglycan Matrix on Peripheral Motor Nerve Regeneration in a Rat Model. The Journal of Bone & Joint Surgery. 2012 Nov;94(22):2084-2091.

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