Effect of tension on nerve regeneration in rat sciatic nerve transection model

Excessive tension across a nerve repair is known to impair nerve regeneration. However, it is uncertain whether nerve grafting is necessary when end-to-end repair would result in only mild to moderate tension. This study investigated the effect of tension on nerve regeneration. Sciatic nerves of 48 Lewis rats were transected and then repaired primarily after resection of 0-, 3-, 6-, or 9-mm lengths of nerve. Postoperative tension levels were quantified using a tensometer. Robust nerve regeneration was observed at 4 weeks in all except the 9-mm repair group, which showed lower nerve fiber counts, percent neural tissue, and nerve density (P < 0.05) and decreased functional recovery. These data indicate that modest levels of tension are well tolerated, but nerve regeneration drops precipitously once a critical tension threshold is exceeded. This threshold was between 0.39 and 0.56 N in the model studied, corresponding to a nerve defect between 6 mm and 9 mm.     

Electrophysiological studies of various graft lengths and lesion lengths in repair of nerve gaps in primates

Electrophysiological studies were used to evaluate neurological recovery in 14 rhesus monkeys with different nerve lesion lengths and graft lengths. After exposure of both sciatic nerves in each animal, baseline evoked nerve action potentials, muscle action potentials, and muscle strength values were determined for the posterior tibial nerves. Each nerve was then crushed over a measured distance. Three weeks later, the crushed segments were resected and the defects repaired with sural nerve grafts. In seven animals, 20-mm resection sites were repaired by 4 x 20-mm grafts in one leg and by 4 x 40-mm grafts contralaterally. In the other seven animals, the lengths of resection sites were 10 mm in one leg and 30 mm contralaterally; both nerve defects in these animals were repaired by 4 x 30-mm grafts. Electrophysiological studies were repeated at one interval of either 4, 7, or 12 months after repair. Postoperative electrophysiological values were compared to baseline values and described by the mean values and by percent recovery. Muscle strength recovery was significantly better in limbs with short lesions. In animals with identical lesion lengths, lesions repaired with shorter grafts (the same length as the defect) did significantly worse than did lesions repaired with longer grafts. This may suggest that any degree of tension at the graft repair site has a deleterious effect on functional nerve regeneration. Nevertheless, it was generally found that nerve lesion length had the greatest negative effect on functional nerve regeneration.     

Experimental study of polarity in reversing cable nerve grafts

To evaluate the effect of cable nerve graft polarity, the bilateral common peroneal nerves in 12 rabbits were excised to create 20-mm nerve gaps. These gaps were repaired with cable grafts using three strands of 20-mm ipsilateral sural nerves. In the left leg, the sural nerves were grafted with the original orientation. In the right leg, the nerve graft polarity was reversed 180 degrees. Six months later, motor conduction velocities were evaluated, and the bilateral anterior tibial muscles and extensor digitorum longus muscles were measured. The nerves were harvested and analyzed histologically. Motor conduction velocity was 37.4+/-4.1 m/s in the reversed group, and 36.6+/-5.5 m/s in the control group. The weight of the muscles was 7.2+/-0.8 g in the reversed orientation, and 7.0+/-1.0 g in the original orientation. None of the differences was statistically significant. Histologically, the axon counts and the axonal density distal to the nerve graft also showed no differences between groups. The sural nerves used did not have a major branch and their diameter was almost the same throughout its length. Reversing nerve graft polarity of a cable graft did not affect nerve regeneration electrophysiologically or histologically.     

Repair of nerve defect with acellular nerve graft supplemented by bone marrow stromal cells in mice

The acellular nerve graft that can provide internal structure and extracellular matrix components of the nerve is an alternative for repair of peripheral nerve defects. However, results of the acellular nerve grafting for nerve repair still remain inconsistent. This study aimed to investigate if supplementing bone marrow mesenchymal stromal cells (MSCs) could improve the results of nerve repair with the acellular nerve graft in a 10-mm sciatic nerve defect model in mice. Eighteen mice were divided into three groups (n = 6 for each group) for nerve repairs with the nerve autograft, the acellular nerve graft, and the acellular nerve graft by supplemented with MSCs (5 × 10(5)) fibrin glue around the graft. The mouse static sciatic index was evaluated by walking-track testing every 2 weeks. The weight preservation of the triceps surae muscles and histomorphometric assessment of triceps surae muscles and repaired nerves were examined at week 8. The results showed that the nerve repair by the nerve autografting obtained the best functional recovery of limb. The nerve repair with the acellular nerve graft supplemented with MSCs achieved better functional recovery and higher axon number than that with the acellular nerve graft alone at week 8 postoperatively. The results indicated that supplementing MSCs might help to improve nerve regeneration and functional recovery in repair of the nerve defect with the acellular nerve graft.     

Functional assessment of misdirected axon growth after nerve repair in the rat

Age, late repair, loss of nerve tissue, tension, and other factors are now known to influence axon regeneration and the quality of recovery after nerve repair. Many of the factors cannot be controlled by surgery. However, a few important ones depend on surgical technique, and some could be minimized, e.g., suture with tension, scarring due to foreign material, and misdirected axon growth. In this study, the authors tried to assess the functional consequences of misdirected axon growth in the sciatic nerve of the rat. They used a strainless coaptation nerve-repair technique with bioabsorbable plate support (polylactic acid), permitting them to study only the consequences of misdirected axon growth, without tension or suture in the area of nerve repair. Sixty rats were divided into three groups. In Group 1, 20 sciatic nerves were repaired without rotation of the distal nerve stump. In Group 2, 20 sciatic nerves were repaired with a 90-degree rotation of the distal nerve stump. In Group 3, 20 sciatic nerves were repaired with a 180-degree rotation of the distal nerve stump. Functional analyses were performed with the sciatic functional index. The results showed the poor consequences of incorrect nerve-end alignment in nerve repair (p < 0.05). Nerve repair with bioabsorbable plate support is known to allow good stump coaptation, without tension and without foreign material. The authors suggest an adaptation or modification of this technique, which might minimize misdirected axon growth, one of the factors whose effects can be mitigated by surgical technique.     

预变神经段修复神经缺损的实验研究

目的探讨不同预变时间组移植神经对神经再生的影响。方法以ＳＤ大鼠的不同预变时间组的尺神经作为移植神经，修复其正中神经的缺损。实验侧按移植神经预变时间的不同分为０、１、２、３、４、８周共６组，每组６只ＳＤ大鼠。移植后１２周，检测实验侧趾屈肌群的张力、最大收缩力、再生神经的形态及神经轴突的截面积。结果用预变１周的尺神经修复正中神经后，其趾屈肌群的张力及最大收缩力的恢复率达到正常对照组的８１．１％及８５．９％。显微镜下观察，预变１周组和其它各时间组相比，其再生的神经轴突最多，发育最成熟。结论用预变１周的神经段修复神经缺损，其神经再生能力最佳     

Sciatic nerve regeneration through alginate with tubulation or nontubulation repair in cat

A novel material for nerve regeneration, alginate, was employed in both tubulation and nontubulation repair of a long peripheral nerve defect injury. Twelve cats underwent severing of the right sciatic nerve to generate a 50-mm gap, which was treated by tubulation repair (n = 6) or nontubulation repair (n = 6). In the tubulation group, a nerve conduit consisting of polyglycolic acid mesh tube filled with alginate sponge was implanted into the gap and the tube was sutured to both nerve stumps. In the nontubulation group, the nerve defect was repaired by a simple interpolation of two pieces of alginate sponge without any suture. The animals in both groups exhibited similar recovery of locomotor function. Three months postoperatively, successful axonal elongation and reinnervation in both the afferent and efferent systems were detected by electrophysiological examinations. Intracellular electrical activity was also recorded, which is directly indicative of continuity of the regenerated nerve and restoration of the spinal reflex circuit. Eight months after operation, many regenerated myelinated axons with fascicular organization by perineurial cells were observed within the gap, peroneal and tibial branches were found in both groups, while no alginate residue was found within the regenerated nerves. In morphometric analysis of the axon density and diameter, there were no significant differences between the two groups. These results suggest that alginate is a potent material for promoting peripheral nerve regeneration. It can also be concluded that the nontubulation method is a possible repair approach for peripheral nerve defect injury.     

Regeneration of peripheral nerve gaps with a polyglycolic acid-collagen tube

OBJECTIVE: The aim of this study was to report by means of objective methods on the effectiveness of a nerve reconstruction procedure using a bioresorbable tube in two patients. Our previous successes in regenerating canine peripheral nerves across long distances (80-mm gaps) using a bioabsorbable tube have led us to investigate the value of such a tube for the treatment of human patients with chronic nerve injuries. METHODS: The device was made from a cylindrically woven polyglycolic acid tube filled with a collagen sponge. It was designed to be resorbed after nerve regeneration. Peripheral sensory nerve defects in two patients with neuroma and pain were reconstructed using this tube. Patient 1 (a 62-year-old man) had a 20-mm defect of the proper digital nerve, and Patient 2 (a 56-year-old woman) had a 65-mm defect of the superficial peroneal nerve. RESULTS: After surgery, both patients recovered from the unpleasant sensations and intolerable pain. In Patient 1, functional recovery was objectively identified at 2 months, and conduction velocity of the nerve recovered to 49.1 m/s. In Patient 2, conduction velocity of the nerve was determined to be 16.9 m/s at 5 months. Current perception threshold testing indicated that sensory nerve function had been recovered by 65 days after surgery. CONCLUSION: This work represents the first precise clinical evaluation, performed under objective evaluation criteria, of sensory recovery achieved using a nerve tube, suggesting that the use of a polyglycolic acid-collagen tube has the potential to become a viable alternative to conventional autografting for the repair of peripheral nerve defects.     

优化法去细胞大鼠神经同种异体移植修复坐骨神经缺损

[目的]以优化法去细胞大鼠神经移植,修复同种异体坐骨神经缺损,观察术后动物的免疫排斥、早期功能恢复及神经再生情况。[方法]以优化去细胞方法处理新鲜取材的成年SD大鼠坐骨神经,移植修复同种异体1.0cm坐骨神经缺损,以自体神经和新鲜异体神经移植为对照,术后1个月行坐骨神经功能指数评价、神经电生理和组织学检查,观察动物在功能恢复、免疫排斥及神经再生方面的情况。[结果]自体神经和去细胞异体神经移植组动物的坐骨神经功能指数无显著差异(P>0.05),大体观察均可见神经连续性良好。电生理检测表明2组动物移植神经均已恢复电传导能力,在传导速度(CV)上无显著差异(P>0.05),但均未达到正常神经水平(P<0.05)。组织学观察则显示2组再生神经纤维均已长入移植段远端。S-100免疫组化显示两者在雪旺氏细胞数、形态和排列等方面无明显差异。2组在CD8 T细胞和巨噬细胞免疫组化染色阳性面积百分比上差异无统计学意义(P>0.05)。计算移植神经中段轴突密度后表明两者无显著差异(P>0.05),但都比正常神经小(P<0.05),比新鲜异体神经移植组大(P<0.05)。[结论]优化去细胞神经移植组与自体神经移植组在免疫排斥、功能恢复及神经再生方面无显著差异。优化法去细胞神经在移植修复同种异体神经缺损时,可以达到免疫耐受,其早期功能恢复和神经再生情况良好,在修复周围神经缺损时可以作为自体神经移植的一种替代疗法。     

Correlation between functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury: experimental study

An experimental study on the correlation between functional and morphologic recovery of crushed sciatic nerves was carried out in rats. The sciatic nerve of 33 rats, divided into three groups, was submitted to controlled crushing injury on a 5-mm long segment, in a universal testing machine for 10 min with three different loads (100, 500, and 15,000 g, respectively). Functional recovery was evaluated, using a modified sciatic functional index (SFI) at weekly intervals up to the 60th postoperative day, at which time, the animals were sacrificed for histologic and morphometric studies of the nerves. Results were compared with those of normal untouched nerves and nerves submitted to segmentary resection without repair. Initial loss of function was observed in all animals with crush injury, but recovery to a nearly normal SFI occurred after progressively longer intervals (25, 39, and 53 days), as a function of load. Nerve-fiber density was increased in the groups submitted to lower loads, but statistically significantly decreased in the animals submitted to the 15,000-g crush. The authors conclude that the SFI is directly correlated with nerve-fiber density and, therefore, is an adequate tool for evaluating sciatic functional deficiency in the rat.     

Vein conduits for repair of nerves with a prolonged gap or in unfavorable conditions: An analysis of three failed cases

Clinical failure of vein conduits for repair of four nerves in three cases is reported. Two digital nerves with gaps of 5.0 cm and 5.8 cm, respectively, and two median nerves with gaps of 4.0 cm and 5.0 cm were repaired with vein conduits. The digital nerves were repaired secondarily with insertion of nerve tissue slices. The median nerve lacerations were associated with compound soft tissue injuries and were repaired primarily by interfascicular vein conduits. There was no detectable recovery of sensibility in autonomous areas of these nerves and no sign of recovery of the innervated muscles during follow-up. Re-exploration revealed that the vein conduits used for repair of the median nerves were constricted by surrounding scar tissue and axon regeneration was precluded. The critical length for nerve regeneration in human beings and wound conditions unfavorable to nerve regeneration are discussed. This report suggests that vein conduits are not indicated in nerve gaps over 5.0 cm or in primary repair of nerves with compound injuries. © 1995 Wiley-Liss, Inc.     

First place--Resident Basic Science Award 1990. Fibronectin-laminin combination enhances peripheral nerve regeneration across long gaps

An exogenous fibronectin-laminin (FN-LAM) solution was added into silicone chambers to determine the effects on peripheral nerve regeneration across 18-mm long gaps. The sciatic nerves of adult rats were sutured into silicone chambers 20 mm in length, creating an 18-mm gap between the proximal and distal nerve stumps. The chambers were filled with either a mixture of fibronectin and laminin (500 micrograms/ml each) or a solution of cytochrome C (1 mg/ml) as the control. After six weeks, the animals were killed and the chambers were examined for regeneration. Seventy percent of the animals from the FN-LAM group demonstrated regeneration across the 18-mm gaps, compared to only 30% in the control group. The combination of FN-LAM significantly increased the number of axons that grew into the distal end of the chamber (FN-LAM, 1325 +/- 522; cytochrome C, 153 +/- 104; p = 0.03). Examination of the distal tributaries of the sciatic nerve revealed axons only in the FN-LAM group; none were found in the control group. Quantitative analysis of neurons, retrogradely labeled with horseradish peroxidase via injection of the sciatic nerve distal to the regenerated segment, revealed a greater number of sensory and motor neurons in the FN-LAM group compared to the control group. Morphometric studies revealed that the mean area of the regenerated segment in the FN-LAM group was 37% larger than the controls, and ultrastructural analysis demonstrated a more mature regenerated nerve. This is the first in vivo demonstration that this combination of fibronectin and laminin significantly enhances the regeneration of myelinated axons across a long nerve gap in the rat sciatic nerve.     

Experimental study on tension and stretching to peripheral nerve

As to the suturing large peripheral nerve defects under tension, several questions have not yet been answered. How long is the critical gap for functional recovery, and how can these gaps be overcome? In order to resolve these questions, an experimental study was undertaken using sciatic nerves of the 83 mongrel adult dogs. A Two Stage Procedure for the neurorrhaphy was invented to overcome the large nerve defect. This method consists of the following two stages. The first stage operation is done by gradual approximation of both stumps against tension with a single and thick suture material. The second stage operation is done three weeks following the first stage operation, consisting of epineural suture under the microscope after refreshment of both stumps. The longest nerve defect in which axonal regeneration was accomplished by this Two Stage Procedure ranged 5 cm (proximal: 5.2% elongation, distal: 12% elongation) in the sciatic nerve of dogs.     

Effects of tension at the site of coaptation on recovery of sciatic nerve function after neurorrhaphy: evaluation by walking-track measurement, electrophysiology, histomorphometry, and electron probe X-ray microanalysis.

The effects of tension at the site of coaptation on recovery of sciatic nerve function after neurorrhaphy were studied by evaluating walking-track measurements, nerve conduction velocity measurements, histomorphometry, and electron probe X-ray microanalysis. Forty adult male Lewis rats underwent right sciatic nerve (SN) transection followed by one of four different nerve repair procedures (N = 10 rats per group). In Group 1, the gap was repaired by end-to-end epineural coaptation. In Group 2, a 5-mm segment of SN was resected, and the defect was repaired under high tension by epineural neurorrhaphy. In Group 3, a 5-mm segment of SN was resected, and the defect was repaired with a 5-mm interposition nerve graft. In Group 4, a 5-mm segment of SN was resected. Then, to lessen the tension that follows neurorrhaphy, an anchoring suture was added. Finally, end-to-end coaptation was performed. Walking-track analysis showed better functional recovery in Group 1 than in Group 2, and better recovery in Group 3 than in Group 2. Group 4 showed a tendency toward better recovery comparing with Group 2. Electron probe X-ray microanalysis revealed higher Na, Cl, and K peaks in axoplasm accompanied by increase in the endoneural fluid pressure (EFP) in Group 2 than those of Group 1. This higher level of Na, Cl and K may be due to impairment of axonal sodium and potassium transport mechanism in Group 2. Increase in EFP may affect nerve regeneration.     

Isogenic venous graft supported with bone marrow stromal cells as a natural conduit for bridging a 20 mm nerve gap

In this study, we introduce a technique for bridging large neural gaps, using an isogenic vein graft supported with isogenic bone marrow stromal cells (BMSC). In three groups a nerve defect of 20 mm was bridged with a vein graft. Our first experimental group comprized an empty venous graft, in group II the venous nerve graft was filled with saline where as in group III the venous nerve graft was filled with BMSC. The animals were tested for functional recovery up to 3 months post repair. Our results show that the BMSC filled venous graft resulted in significantly better regeneration of the nerve defect compared to controls, as confirmed by the functional recovery measured by somatosensory evoked potentials, toe spread, pin prick, and gastrocnemius muscle index. Conclusively, the results confirm that the vein graft supported with BMSC is associated with better functional nerve regeneration. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.     

The single-fascicle method of nerve grafting

In this study a single-fascicle technique for neural deficits repair was evaluated using a rat sciatic nerve model. Twenty-four Lewis rats were divided into 4 groups: group 1, 1.5-cm deficit without repair; group 2, conventional autograft; group 3, large-fascicle autograft; and group 4, small-fascicle autograft. Nerve regeneration was evaluated by pin-prick and toe-spread tests. Nerve samples were estimated by histomorphometry. Group 1 presented no recovery. Groups 3 and 4 demonstrated significantly better pin-prick results compared with those from conventional repair. Histology revealed a significantly higher number of axons and myelin thickness in the small-fascicle (2.8 +/- 0.4 x 10(3) axons, 4.22 +/- 0.41 microm) and large-fascicle (5.1 +/- 1.7 x 10(3) axons, 4.62 +/- 0.28 microm) groups compared with the conventional autograft group (2.1 +/- 0.3 x 10(3) axons, 2.93 +/- 0.20 microm). The small-fascicle group had a significantly greater mean axon area (58.59 +/- 15.81 microm2) than the large-fascicle group (29.66 +/- 12.67 microm2) and the conventional group (25.35 +/- 7.52 microm2). In this study, peripheral nerve repair using a single-fascicle graft resulted in faster functional recovery and better morphometric outcome compared with conventional nerve repair.     

The effect of androgen status on the structural and functional success of cavernous nerve grafting in an experimental rat model

PURPOSE: Iatrogenic erectile dysfunction following radical prostatectomy is primarily neurogenic in origin. Attempts to improve postoperative potency aim to preserve or regenerate the autonomic cavernous nerves. Testosterone is integral for erectile function and it has profound positive effects on nerve regeneration. Androgen ablation impairs nerve regeneration. In this animal study we evaluated whether testosterone deprivation effects axonal regeneration in cavernous nerve grafts or the erectile response to cavernous nerve graft stimulation. MATERIALS AND METHODS: A total of 45 male Sprague-Dawley rats underwent bilateral cavernous nerve neurotomy, followed by unilateral nerve graft using the genitofemoral nerve. Rats were then randomized to castrate, intact and testosterone treated arms. At 3 months grafts were explored and electrostimulation was performed with intracavernous pressure responses recorded. Grafted nerves were then harvested for immunohistochemical analysis. RESULTS: Univariate analysis demonstrated a significant difference in the maximal intracavernous pressure response between groups. Mean +/- SEM maximal intracavernous pressure was 47 +/- 7.9, 23.7 +/- 4.9 and 59 +/- 7.4 mm Hg in the intact, castrate and testosterone treated groups, respectively (p = 0.003). Total axon counts did not differ between treatment groups with a mean total axon count of 789 +/- 97, 706 +/- 134 and 726 +/- 111, respectively. Castrate animals had lower neuronal nitric oxide synthase axon counts compared to intact animals (p = 0.089). The mean axon count was 480 +/- 78, 285 +/- 53 and 435 +/- 71 in the intact, castrate and testosterone treated groups respectively. CONCLUSIONS: Castration resulted in a decreased erectile response to electrostimulation following nerve grafting. This may be due to decreased graft neuronal nitric oxide synthase positive axonal regeneration. This has important implications in patients in whom cavernous nerve grafting could be considered.     

Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats

BACKGROUND: Citicoline has been shown to have beneficial effects in a variety of CNS injury models. The aim of this study was to test the effects of citicoline on nerve regeneration and scarring in a rat model of peripheral nerve surgery. METHODS: Seventy adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve section and epineural suturing. Rats were assigned to the control or experiment groups to receive a topical application of 0.4 mL of saline or 0.4 mL (100 micromol/L) of citicoline, respectively. Macroscopic, histological, functional, and electromyographic assessments of nerves were performed 4 to 12 weeks after surgery. RESULTS: In the control versus citicoline-treated rats, SFI was -90 +/- 1 versus -84 +/- 1 (P < .001), -76 +/- 4 versus -61 +/- 3 (P < .001), and -66 +/- 2 versus -46 +/- 3 (P < .001) at 4, 8, and 12 weeks after surgery, respectively. At 12 weeks after surgery, axon count and diameter were 16400 +/- 600 number/mm(2) and 5.47 +/- 0.25 microm versus 22250 +/- 660 number/mm(2) (P < .001) and 6.65 +/- 0.28 microm (P < .01) in the control and citicoline-treated groups, respectively. In citicoline-treated rats, histomorphological axonal organization score at the repair site was (3.4 +/- 0.1) significantly better than that in controls (2.6 +/- 0.3) (P < .001). Peripheral nerve regeneration evaluated by EMG at 12 weeks after surgery showed significantly better results in the citicoline group (P < .05). Nerves treated with citicoline demonstrated reduced scarring at the repair site (P < .001). CONCLUSION: Our results demonstrate that citicoline promotes regeneration of peripheral nerves subjected to immediate section suturing type surgery and reduces postoperative scarring.     

Tubulation repair of peripheral nerves in the rat using an inside-out intestine sleeve

This study compared the regeneration of peripheral nerves in the Sprague-Dawley rat through a nerve guide prepared from rat small intestine to nerve regeneration using a standard autogenous nerve-graft repair strategy. In one experimental group (n = 15), inside-out rat intestine sleeves were used as nerve guides to bridge a 10-mm defect created in the right sciatic nerve. These nerve guides were prepared by harvesting 14-mm segments of small intestine from Sprague-Dawley rats not otherwise used in the study. The segments were turned inside-out to expose the serosa as the lumen of the guide, and transected nerve stumps were secured 2 mm into the guide on each end with an epineural-to-guide stitch. The control group (n = 15) had an identical gap repaired with a standard autologous nerve graft. Five animals from each group were sacrificed at 4, 8, and 12 weeks. The extent of axonal regeneration was assessed by axon-counting, retrograde tracer analysis, electromyography, and qualitative histologic assessment. The inside-out intestine sleeve group exhibited faster conduction velocities and greater axon counts when compared to the autologous nerve-graft controls. These novel nerve guides proved simple to manufacture and were completely absorbed by 12 weeks.     

Recovery of muscle contractile function following nerve gap repair with chemically acellularized peripheral nerve grafts

Acellular nerve grafts have emerged as a possible alternative for reconstruction of short (<2 cm) peripheral nerve gaps. Axonal regeneration has been demonstrated within the nerve constructs. However, very little work has been done to demonstrate both axonal regeneration and recovery of motor function following peripheral nerve gap repair with acellular nerve constructs. The authors hypothesized that chemically acellularized nerve grafts can support axonal regeneration and provide functional reinnervation of rat hindlimb muscles with equivalent efficiency to peripheral nerve autografts. Peroneal nerves were harvested from adult rats and chemically acellularized. Two- and 4-cm peroneal nerve gaps were reconstructed with either a cellular autograft or an acellular isograft. Functional recovery was evaluated with walking-track analyses and measurement of maximum tetanic isometric force (F 0 ) of the extensor digitorum longus (EDL) muscle. Walking-track analysis revealed no statistically significant difference in functional recovery in rats undergoing reconstruction of 2-cm nerve gaps with acellular isografts or cellular autografts. Maximum tetanic isometric force measurements revealed a 60 percent force deficit in EDL muscles reinnervated by 2-cm acellular nerve grafts, compared to cellular autografts. Four-centimeter acellular grafts failed to support any significant EDL muscle reinnervation. This study demonstrates that chemically acellularized peripheral nerve supports axonal regeneration and functional reinnervation across 2-cm nerve gaps, and may potentially serve as an appropriate scaffold for reintroducing cellular elements, adhesion molecules, or growth factors for repair of longer nerve gaps.