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Comparison of sciatic nerve regeneration through silicone tubes and nerve allografts
Abstract
Sciatic nerve regeneration through implanted silicone tubes was compared to allogenic nerve grafting in 30 adult female Sprague-Dawley rats. Regeneration was assessed at 10, 24, and 90 days post-transection. Axonal regrowth through the implanted neural prostheses was evaluated with electromyography and histologic examination.
... Conduits are typically fabricated with either single or multiple lumens [4,5], and the lumen can be filled with a hydrogel (e.g. matrigel, fibrin) [6] or used empty [7]. ...
... Guidance channels have been fabricated from a range of natural and synthetic polymers [1] using a variety of fabrication techniques, including solvent casting, extrusion, freeze drying, and dip molding [10][11][12]. Materials used for fabrication include both natural (e.g., collagen) [13][14][15] and synthetic polymers (e.g., silicone, ethylene vinyl coacetate (EVAc), poly(lactide-co-glycolide) (PLG)) [7,16]. The processing of these materials can provide conduits with a range of degradation rates, porosities, and mechanical properties. ...
Tissue engineering strategies for nerve repair employ polymer conduits termed guidance channels and bridges to promote regeneration for peripheral nerve injury and spinal cord injury, respectively. An approach for fabrication of nerve conduits with single and multiple lumens capable of controlled release of neurotrophic factors was developed. These conduits were fabricated from a mixture of poly(lactide-co-glycolide) (PLG) microspheres and porogen (NaCl) that was loaded into a mold and processed by gas foaming. The porosity and mechanical properties of the constructs were regulated by the ratio of porogen to polymer microsphere. The neurotrophin, nerve growth factor (NGF), was incorporated into the conduit by either mixing the protein with microspheres or encapsulating the protein within microspheres prior to gas foaming. A sustained release was observed for at least 42 days, with the release rate controlled by method of incorporation and polymer molecular weight. Released NGF retained its bioactivity, as demonstrated by its ability to stimulate neurite outgrowth from primary dorsal root ganglion (DRG). In vivo results indicate that conduits retain their original architecture, and allow for cellular infiltration into the channels. Polymer conduits with controllable lumen diameters and protein release may enhance nerve regeneration by guiding and stimulating neurite outgrowth.
... [98] However, many works in rats also reported the formation of scarred tissue, compression of the new axons or even no regeneration at all. [99][100][101] Moreover, researchers also refer that in some patients, silicone tubes had to be removed because of loss of nerve function due to irritation at the implantation site. As this material is non-biodegradable, a chronic inflammation associated to excessive scarred tissue formation can occur during time, in some cases, after one week. ...
Experiments concerning peripheral nerve regeneration have been reported since the end of the 19(th) century. The need to implement an effective surgical procedure in terms of functional recovery has resulted in the appearance of several approaches to solve this problem. Nerve autograft was the first approach studied and is still considered the gold standard. Since autografts require donor harvesting, other strategies involving the use of natural materials have also been studied. Nevertheless, the results were not very encouraging and attention has moved towards the use of nerve conduits made from polymers, whose properties can be easily tailored and which allow the nerve conduit to be easily processed into a variety of shapes and forms. Some of these materials are already approved by the US Food and Drug Administration (FDA), as is presented here. Furthermore, polymers with conductive properties have very recently been subject to intensive study in this field, since it is believed that such properties have a positive influence in the regeneration of the new axons. This manuscript intends to give a global view of the mechanisms involved in peripheral nerve regeneration and the main strategies used to recover motor and sensorial function of injured nerves.
... Ces premiers conduits nerveux étaient construits en os, silicone, veine, artère (Cataltepe et al., 1993), amnion (Ozcan et al., 1993), polyglactine 910 (Molander et al., 1982) et collagène (Mackinnon et Dellon, 1990b). De nombreux matériels d'origine biologique ou synthétiques imperméables ou semiperméables , résorbables ou non résorbables (polyéthylène, polyvinyle,…) ont été utilisés par la suite (Dahlin et al., 1988 ; Danielsen et al., 1988a Danielsen et al., , 1988b Danielsen et al., , 1988c Danielsen et al., , 1988d Gibson et al., 1989 ; Merle et al., 1989a Merle et al., , 1989b Keeley et al., 1991 ; Den Dunnen et al., 1993 ; Nicoli-Aldini et al., 1993 ; den Dunnen et al., 1995 den Dunnen et al., , 1996a den Dunnen et al., , 1996b Doolabh et al., 1996 ; Meek et al., 1996 ; den Dunnen et al., 1997 ; Meek et al., 1997 ; Meek et al., 1999a Meek et al., , 1999b Meek et al., , 1999c Lundborg, 2000c). Ils évitent de prélever un nerf autologue et d'entraîner un neurome et une perte de fonction au niveau du site donneur. ...
Introduction
Nerve injury compromises sensory and motor functions. Techniques of peripheral nerve repair are based on our knowledge regarding regeneration. Microsurgical techniques introduced in the late 1950s and widely developed for the past 20 years have improved repairs. However, functional recovery following a peripheral mixed nerve injury is still incomplete.
State of art
Good motor and sensory function after nerve injury depends on the reinnervation of the motor end plates and sensory receptors. Nerve regeneration does not begin if the cell body has not survived the initial injury or if it is unable to initiate regeneration. The regenerated axons must reach and reinnervate the appropriate target end-organs in a timely fashion. Recovery of motor function requires a critical number of motor axons reinnervating the muscle fibers. Sensory recovery is possible if the delay in reinnervation is short. Many additional factors influence the success of nerve repair or reconstruction. The timing of the repair, the level of injury, the extent of the zone of injury, the technical skill of the surgeon, and the method of repair and reconstruction contribute to the functional outcome after nerve injury.
Conclusion
This review presents the recent advances in understanding of neural regeneration and their application to the management of primary repairs and nerve gaps.
... [93][94][95][96] Both permanent and synthetic resorbable materials have been proposed as nerve conduits and cuffs, including Gore-Tex, NeuraGen, silicon, polyglycolic acid, and collagen. [97][98][99][100][101] An indication for surgical intervention is dysesthesia, although even after operation some patients still present severe symptoms. 81 When this occurs, a pharmacologic approach is appropriate, although currently available drugs at best seem to produce only partial relief of symptoms. ...
The removal of mandibular third molars is probably the most frequently performed procedure in oral and maxillofacial surgery, and it is the most common surgical procedure associated with lingual nerve deficit. Lingual sensory impairment remains a clinical problem in oral and maxillofacial surgery and has serious medical and legal implications. In fact, damage to the lingual nerve is a common cause of litigation in dentistry. The purpose of this article was to review the literature about lingual nerve deficit following mandibular third molar removal and discuss the associated medicolegal aspects.
... Silikon ist eines der meist verwendeten Konduitmaterialien (Chen et al. 1989, Gibson et al. 1989, Longo et al. 1983a, Lundborg et al. 1982, Williams et al. 1983 (Cha und Pitt 1990, Domb et al. 1994, Pitt et al. 1981 Ha 1998). ...
In der vorliegenden Arbeit erfolgte eine Analyse der neuronalen Regeneration in Poly-Caprolacton (PCL)-Nervenleitschienen bei Applikation von Schwann-Zellen, einer Fibrin-Matrix und des neurotrophen Faktors LIF (Leukemia Inhibitory Factor). Hierzu wurden Schwann-Zellen aus dem N. ischiadicus neonataler Ratten kultiviert. Als Läsionsmodell diente ein 10mm langer Defekt im bukkalen Ast des N. facialis der Ratte, der überbrückt wurde mit PCL-Konduiten. Nach 4 Wochen wurden die Implantate histologisch und morphometrisch innerhalb von 4 Schnittebenen untersucht (S1=2,5mm, S2=5mm, S3=7,5mm, S4=10mm). Zur Darstellung des Regenerationsprozesses dienten als Methoden: Immunhistochemie gegen Neurofilament (S200) und Cholinacetyltransferase (ChAT), Toluidinblau Färbung der Myelinscheide und retrograde Markierung der zentralen Nervenzellkerne mittels FAST BLUE. Eine erfolgreiche Regeneration über alle Segmente wurde in den Fibrin/Schwann-Zellen-Matrix gefüllten PCL-Konduiten mit und ohne LIF beobachtet. In der dreidimensionalen Fibrin-Matrix waren die Schwann-Zellen homogen verteilt und zeigten eine hohe Vitalität.
... Synthetic guides are usually made with polymeric materials, and may be nonresorbable (9,10) or resorbable (11,12). Non resorbable conduits remain foreign bodies around the regenerated nerve, hence impairing function recovery. ...
Two different types of conduits, one biological, obtained with homologous glutaraldehyde preserved vein segments and the other synthetic bioabsorbable, made with Poly [L-lactide-co-6-caprolactone], were evaluated as guides for nerve repair in alternative to autologous grafts in an experimental animal model. Under general anesthetic, the ischiatic nerve of a number Wistar rats was transected to create a 1 cm gap, which was then repaired by means of the conduits or autologous grafts. Controls were performed at 1, 3 and 6 months; nerve regeneration was effective with both conduits, but the count of myelinated axons showed a significant difference between the synthetic and biological tubes (p < 0.001). The Poly [L-lactide-co-6-caprolactone] guide was still intact 30 days after implant; progressive signs of degradation were present at 90 and 180 days. These results show that the synthetic conduits are better than those obtained with preserved vein segments and might be considered in alternative to autologous grafts in peripheral nerve reconstruction.
... These tubes, typically referred to as nerve guides or nerve guidance channels, act to sequester chemotrophic and chemotactic molecules while reducing the formation of scar tissue around the reforming nerve. Tubular nerve guides have been constructed from a variety of materials, including silicone rubber (Lundborg et al., 1982b; Williams et al., 1983; Gibson and Daniloff, 1989; Danielsen et al., 1993; Dahlin et al., 1995), collagen (Archibald et al., 1991; Li et al, 1992; Chamberlain et al., 1998), and bioresorbable polymer tubes made of poly(L-lactide) acid (PLLA) (Seckel et al., 1984; da Silva et al., 1985), poly(glycolic acid; PGA) (Dellon and Mackinnon, 1988; Mackinnon and Dellon, 1990; Keeley et al., 1991), polyglactin (Molander et al., 1983), or blends of these components (den Dunnen et al., 1995, 1996, 1997; Aldini et al., 1996; Rodriguez et al., 1999). The latter group has the advantage of degrading ...
After injury, axonal regeneration occurs across short gaps in the peripheral nervous system, but regeneration across larger gaps remains a challenge. To improve regeneration across extended nerve defects, we have fabricated novel microfilaments with the capability for drug release to support cellular migration and guide axonal growth across a lesion. In this study, we examine the nerve repair parameters of non-loaded filaments. To examine the influence of packing density on nerve repair, wet-spun poly(L-Lactide) (PLLA) microfilaments were bundled at densities of 3.75, 7.5, 15, and 30% to bridge a 1.0-cm gap lesion in the rat sciatic nerve. After 10 weeks, nerve cable formation increased significantly in the filament bundled groups when compared to empty-tube controls. At lower packing densities, the number of myelinated axons was more than twice that of controls or the highest packing density. In a consecutive experiment, PLLA bundles with lower filament-packing density were examined for nerve repair across 1.4- and 1.8-cm gaps. After 10 weeks, the number of successful regenerated nerves receiving filaments was more than twice that of controls. In addition, nerve cable areas for control groups were significantly less than those observed for filament groups. Axonal growth across 1.4- and 1.8-cm gaps was more consistent for the filament groups than for controls. These initial results demonstrate that PLLA microfilaments enhance nerve repair and regeneration across large nerve defects, even in the absence of drug release. Ongoing studies are examining nerve regeneration using microfilaments designed to release neurotrophins or cyclic AMP.
... Thus, a 10 mm gap in the facial nerve is a larger distance to overcome than a 10 mm gap in the sciatic nerve. This explains why a 10 mm nerve gap in the rat´s sciatic nerve regenerates within an empty silicone conduit or even without bridging (36,37). In the model presented no regeneration has been observed either when the defect was left unbridged or if it was bridged with an empty PCL conduit. ...
The goal of this study was to investigate if a three dimensional matrix, loaded homogeneously with Schwann cells and the neurotrophic factor LIF (leukemia inhibitory factor), enhances regeneration in a biodegradable nerve guidance channel as compared to non-structured cell suspensions. Therefore a 10 mm nerve gap in the buccal branch of the rat's facial nerve was bridged with tubular PCL (poly-epsilon-caprolactone) conduits filled with no matrix, Schwann cells, the three dimensional fibrin/Schwann cell matrix or the fibrin/Schwann cell matrix added with LIF Four weeks after the nerve defects were bridged histological and morphometric analyses of the implants were performed. In conclusion, the three dimensional fibrin/Schwann cells matrix enhanced the quantity and the quality of peripheral nerve regeneration through PCL conduits. The application of LIF prevented hyperneurotization. Therefore, tissue engineered fibrin/Schwann cells matrices are new invented biocompatible and biodegradable devices for enhancing peripheral nerve regeneration as compared to non-structured cell suspensions without neurotrophic factors.
... Ces premiers conduits nerveux étaient construits en os, silicone, veine, artère (Cataltepe et al., 1993), amnion (Ozcan et al., 1993), polyglactine 910 (Molander et al., 1982) et collagène (Mackinnon et Dellon, 1990b). De nombreux matériels d'origine biologique ou synthétiques imperméables ou semiperméables , résorbables ou non résorbables (polyéthylène, polyvinyle,…) ont été utilisés par la suite (Dahlin et al., 1988 ; Danielsen et al., 1988a Danielsen et al., , 1988b Danielsen et al., , 1988c Danielsen et al., , 1988d Gibson et al., 1989 ; Merle et al., 1989a Merle et al., , 1989b Keeley et al., 1991 ; Den Dunnen et al., 1993 ; Nicoli-Aldini et al., 1993 ; den Dunnen et al., 1995 den Dunnen et al., , 1996a den Dunnen et al., , 1996b Doolabh et al., 1996 ; Meek et al., 1996 ; den Dunnen et al., 1997 ; Meek et al., 1997 ; Meek et al., 1999a Meek et al., , 1999b Meek et al., , 1999c Lundborg, 2000c). Ils évitent de prélever un nerf autologue et d'entraîner un neurome et une perte de fonction au niveau du site donneur. ...
Nerve injury compromises sensory and motor functions. Techniques of peripheral nerve repair are based on our knowledge regarding regeneration. Microsurgical techniques introduced in the late 1950s and widely developed for the past 20 years have improved repairs. However, functional recovery following a peripheral mixed nerve injury is still incomplete.
Good motor and sensory function after nerve injury depends on the reinnervation of the motor end plates and sensory receptors. Nerve regeneration does not begin if the cell body has not survived the initial injury or if it is unable to initiate regeneration. The regenerated axons must reach and reinnervate the appropriate target end-organs in a timely fashion. Recovery of motor function requires a critical number of motor axons reinnervating the muscle fibers. Sensory recovery is possible if the delay in reinnervation is short. Many additional factors influence the success of nerve repair or reconstruction. The timing of the repair, the level of injury, the extent of the zone of injury, the technical skill of the surgeon, and the method of repair and reconstruction contribute to the functional outcome after nerve injury.
This review presents the recent advances in understanding of neural regeneration and their application to the management of primary repairs and nerve gaps.
Background:
Many rehabilitative attempts have been made to prevent or reduce residual deficits in patients with established and long-term facial palsy (FP). In many clinical settings in-situ injection of collagen-based medical devices (MDs) have been demonstrated to provide nutritional support for tissues.
Aim:
To test the effectiveness of a collagen-based treatment for patients complaining of long standing FP, who are following a proprioceptive neuromuscular facilitation protocol (Kabat method) (Group A), compared to a FP group only undergoing the Kabat method (Group B).
Design:
Randomised controlled trial.
Setting:
Tertiary referral outpatient center and University Hospital.
Population:
41 patients with a medical diagnosis of long-term unilateral peripheral FP.
Methods:
Twenty-one Group A patients were compared, after randomization, to nineteen matched Group B patients after 8 weeks of treatment. The outcomes were electromyographic findings, validated questionnaires (Facial Disability Index, FDI and General health-related quality of life assessment, QOL) and clinical grading (House-Brackmann, HB, and synkinesis grading scale). A correlation analysis was performed between pre-/post-treatment differences (Δ) in outcome and clinical-demographic measures.
Results:
A significant within-subjects improvement, both in electrophysiological and questionnaire scores, was found in both groups. When compared with Group B, Group A patients exhibited a significant reduction of post-treatment polyphasic potentials of voluntary activity of orbicularis oculi (p = 0.017) and oris (p = 0.015) and a significant increase in post-treatment duration of voluntary activity of orbicularis oris (p = 0.018). Group A subjects demonstrated a significant improvement in questionnaire subscales regarding overall disease perception. Although positive correlations between the ΔFDI and Δpercentage of polyphasic potentials of voluntary activity were found in both groups, negative correlations in Group A were found between disease duration and Δduration of voluntary activity of orbicularis oculi and oris.
Conclusions:
The combination of physical rehabilitative procedures with in-situ collagen injections, possibly acting in redirecting the phenomena of reinnervation/reorganization, demonstrated encouraging results in patients affected by long term FP.
Clinical rehabilitation impact:
In-situ collagen injection could be a safe option enlarging the 'window of opportunity' to improve the voluntary muscle contraction pattern and general and specific disability referred by patients affected by long standing FP.
Carbon nanotubes (CNTs), with their unique and outstanding properties, such as strong mechanical strength and high electrical conductivity, have become very popular for the repair of tissues, particularly for those requiring electrical stimuli. Polydimethylsiloxane (PDMS)-based elastomers have been used in a wide range of biomedical applications because of their optical transparency, physiological inertness, blood compatibility, non-toxicity, and gas permeability. In present study, most of artificial nerve guidance conduits (ANGCs) are not transparent. It is hard to confirm the position of two stumps of damaged nerve during nerve surgery and the conduits must be cut open again to observe regenerative nerves after surgery. Thus, a novel preparation method was utilized to produce a transparent sheet using PDMS and multi-walled carbon nanotubes (MWNTs) via printing transfer method. Characterization of the PDMS/MWNT (PM) sheets revealed their unique physicochemical properties, such as superior mechanical strength, a certain degree of electrical conductivity, and high transparency. Characterization of the in vitro and in vivo usability was evaluated. PM sheets showed high biocompatibility and adhesive ability. In vivo feasibility tests of rat brain tissue and sciatic nerve revealed the high transparency of PM sheets, suggesting that it can be used in the further development of ANGCs. This article is protected by copyright. All rights reserved.
Purpose:
This report describes the results of using a Gore-Tex (Gore Company, Flagstaff, AZ) tube as a conduit for repair of continuity defects in the inferior alveolar or lingual nerves.
Patients and methods:
Seven nerve repairs were performed in five patients (M:F = 1:4) with an age range of 16 to 56 years. The duration from injury to repair ranged from 4 to 30 months. Two inferior alveolar and five lingual nerves were repaired.
Results:
All seven patients had anesthesia by objective testing preoperatively and had a continuity defect at the time of operation. The size of the defects ranged from 2 to 15 mm. Two of the seven patients had some return of sensation, occurring in defects of 3 mm or smaller.
Conclusion:
The results of this pilot study indicate that Gore-Tex tubing may not be effective in the repair of continuity defects except in those defects 3 mm or smaller, in which it may act as a protective barrier membrane rather than as a conduit.
Peripheral nerve injury may cause gaps between the nerve stumps. Axonal proliferation in nerve conduits is limited to 10-15 mm. Most of the supportive research has been done on rat or mouse models which are different from humans. Herein we review autografts and biomaterials which are commonly used for nerve gap repair and their respective outcomes. Nerve autografting has been the first choice for repairing peripheral nerve gaps. However, it has been demonstrated experimentally that tissue engineered tubes can also permit lead to effective nerve repair over gaps longer than 4 cm repair that was previously thought to be restorable by means of nerve graft only. All of the discoveries in the nerve armamentarium are making their way into the clinic, where they are, showing great potential for improving both the extent and rate of functional recovery compared with alternative nerve guides.
This study describes the results of using NeuraGen (Integra LifeSciences, Plainsboro, NJ) as a nerve cuff for repair of lingual and inferior alveolar nerve injuries following third molar surgery.
Eight female patients received a total of 9 NeuraGen cuffs for repair of lingual (6) or inferior alveolar (3) nerves. All injuries were treated within 3 to 7 months following injury. All patients were evaluated by mechanoceptive and nociceptive testing via brush directional discrimination, pin-prick pressure and thermal sensation. Lateral trap-door osteotomy of the mandible was utilized to access the inferior alveolar nerve. The lingual nerve was approached via a lingual gingival sulcus incision. Following external neurolysis and primary neurorrhaphy, NeuraGen was split longitudinally, and encased the nerve with at least a 1.5 cm margin. One or 2 6-0 prolene horizontal mattress sutures were used to reapproximate the NeuraGen edges and Healon (hyaluronic acid; Advanced Medical Optics, Santa Ana, CA) was applied to the perineural tissues.
Five injuries resulted in objective anesthesia preoperatively with the other 4 having varying degrees of hypoesthesia. Six of the nerve injuries also resulted in dysesthesia. Four patients were followed for at least 1 year and the other 4 patients for about 2.5 years. The most recent data was used for this study. Postsurgical outcome was assessed utilizing some of the criteria proposed by Pogrel to classify patients as having good improvement, some improvement, no improvement, or worsening of symptoms. Four cases were found to have good improvement, 4 with some improvement and 1 had no improvement. None of the cases had worsening of symptoms.
While reports of the use of other alloplastic materials for nerve repair were found to be variable, NeuraGen seems to have good preliminary results. Bioresorption is complete which decreases the likelihood of interneural scarring. Also, NeuraGen is not associated with episodes of compression neuropathy reported with other rigid non biodegradable materials. Its use in hand surgery literature and in experimental animal studies showed no statistical significance in outcome when compared to end-to-end anastomosis or nerve grafts. The reported advantage of NeuraGen was the elimination of problems associated with graft harvesting. In this small series, 8 out of 9 nerve repairs showed sensory improvement which suggests a favorable role of NeuraGen as a nerve cuff and protective barrier around the nerve injury site. While primary end-to-end anastomosis has comparable results, a nerve cuff has the advantage of preventing axonal escape at suture lines, it minimizes scar ingrowth and nerve entrapment, and it concentrates growth factors at the injury site.
The passage of molecules into the endoneurial environment of the axons of normal peripheral nerve is regulated by two permeability barriers, the perineurial-nerve barrier and the endoneurial blood-nerve barrier. These barriers exist because of the presence of tight junctions between adjacent perineurial cells and adjacent endothelial cells. In the present study we investigated whether permeability barriers form in nerve cables, which develop inside silicone chambers. The sciatic nerves of adult rats were cut, and the proximal and distal ends sutured into opposite ends of silicone chambers that were filled with dialyzed plasma. The presence of barriers was determined with the tracer horseradish peroxidase (HRP), which was injected intravenously and detected histochemically in tissues by light and electron microscopy. At four weeks, a regenerated nerve cable extended across the 10 mm length of each chamber. However, no permeability barriers were present since the reaction product for HRP was visible throughout the cable. At twenty-six weeks, all the axons in cables were gathered into minifascicles. Each minifascicle of axons was surrounded by perineurial cells. Blood vessels were excluded from the minifascicles by the perineurial cells and the vessels were permeable to HRP, thus indicating that their endothelial cells had not formed tight junctions. Despite the leakage of HRP from the excluded vessels, the tracer did not reach the axons because the perineurial cells encircling the minifascicles developed tight junctions. In some animals, the chambers were removed at four weeks to determine whether the chamber influenced barrier development. This manipulation had no effect since cables, with or without chambers, exhibited similar findings at twenty-six weeks. Our results indicate that nerve cables regenerate a perineurial but not an endoneurial permeability barrier. We conclude that axons in long-term cables are protected by only a perineurial permeability barrier.
Tubes containing specific monoclonal antibodies to the neural cell adhesion molecule (N-CAM) were applied to transected sciatic nerves to attempt to perturb the recovery of muscle function. Physiological recordings were used to estimate the return of function. The decline of implanted antibody over 28 days was estimated and negatively correlated with the degree of functional recovery. No significant immune responses were detected in response to the implanted material. The data implicated N-CAM as a significant component of nerve regeneration.
This study evaluated the ability of Schwann cell transplants to enhance the recovery of function in injured nerves and compared the results to those produced by sural nerve grafts. Schwann cells were isolated from sciatic nerves, prelabeled with gold fluorescent dye admixed with collagen gel, and placed in resorbable collagen tubes. Twenty-four adult rats underwent severing of the bilateral sciatic nerves, with a 10-mm gap between the nerve stumps. The rats were then divided into two groups. A collagen tube with implanted Schwann cells was implanted in one leg of the Group I rats, and the contralateral leg served as a control and was repaired with a collagen tube filled with collagen gel only. The Group II animals received conduits packed with labeled Schwann cells in one leg to bridge the 10-mm gap; the contralateral leg was repaired with an autogenous sural nerve graft. Recovery of function was assessed physiologically and morphologically.
Nerve conduction velocity and nerve action potential amplitude measurements showed that the Schwann cell implants induced return of function comparable to that of the sural nerve grafts. Morphological assessments of myelination suggested a tendency toward greater numbers of myelinated axons in Schwann cell implants than in sural nerve grafts. Anatomical analyses of gold fluorescent dye showed both high viability of prelabeled Schwann cells at 120 days after transplantation and migration as far as 30 mm away from the implant site.
Positive results of tubulization in peripheral nerve reconstruction have been established in animals by many investigators. Clinically, tubulization by means of a venous tubulus is accepted as a reliable technique, but histological results are not known and functional analysis is limited. The aim of this investigation was to study the histological effect of venous tubuli in peripheral nerve reconstruction.
In 20 rabbits the saphenous nerves were transected and anastomosed. In ten rabbits (series 1) a venous tubulus was placed around the nerve suture. In another ten rabbits (series 2) a venous tubulus was sutured over a 3 mm nerve gap. Conventional suturing was done in ten contralateral saphenous nerves (series 3, controls). Epineurial stitching was performed. The healing was studied after 3 months and after that histological analysis was performed by means of monoclonal antibody staining.
The results of our experiments show that covering a nerve anastomosis with a venous tubulus did not enhance healing in comparison to the conventional end-to-end anastomosis, but in contrast evoked extensive fibrous tissue, thereby hampering regeneration of axons.
A variety of materials have been evaluated as potential nerve grafts. To date, none has been shown to be consistently equal with regard to functional outcome when compared to standard autogenous nerve grafts. In this study, nerves stored in glycerol were evaluated for their peripheral nerve regenerative capacity. Femoral nerves were harvested from Fischer rats and stored for a minimum of 100 days in 98% glycerol at 4 degrees C. They were grafted into femoral nerve gaps of Lewis rats. After 3 months, histologic, electrophysiologic, and morphometric (axon diameter) analyses revealed less regenerative response than nerve gaps grafted with fresh, syngeneic controls. The differences disappeared by 6 months, although neither graft technique achieved recovery comparable to unoperated nerves. Immunohistochemical evaluation demonstrated a modest immune response at 3 months, which subsided by 6 months. These findings are encouraging for the development of glycerol-preserved nerve graft banking.
The recovery of the mechanosensitive afferent fibres in the lingual branch of the trigeminal nerve has been studied using electrophysiological techniques in cats, after two methods of nerve repair. After nerve section the lingual nerve was repaired by either epineurial sutures or by entubulation. 12 weeks after either method of repair the properties of the regenerated fibres were significantly different from normal, but following repair with epineurial suture they were closer to normal than after repair by entubulation. After entubulation the fibres had a greater reduction in conduction velocity, a greater increase in force threshold, and the adaptation times were faster. The results suggest that epineurial suture should be preferred clinically.
A new conduit made with a bioabsorbable copolymer, poly (L-lactide-co-6-caprolactone), was evaluated in an animal model as a guide for nerve regeneration. The conduit had an inner diameter of 1.3 mm and a wall thickness of 175 microns. Segments of length 1.2 cm were interposed between the proximal and distal stumps of transected ischiatic nerves in Wistar rats, bridging a nerve gap of 1 cm. All of the procedure was performed under general anaesthesia using microsurgical techniques. Controls were performed at 1, 3 and 6 months and it was demonstrated that the conduit was still undamaged after 30 d. Progressive signs of degradation appeared at 90 and 180 d. Nerve regeneration in the lumen was effective as confirmed by histological and electron microscopical investigations. These preliminary results emphasize the interesting properties of the conduit with regard to the achievement of a neural prosthesis.
This study analyses the interest of isologous venous grafts filled with saline or with Schwann cells versus nerve grafts as guides for regeneration of the sciatic nerve in 35 Wistar rats. Electrophysiological parameters (conduction velocities and distal latencies of motor responses) and the functional index of De Medinacelli were measured several times from 1 month to 1 year after surgery. An histological analysis was performed on 2 control rats and on 3 rats killed 6 or 12 months after surgery: the total number of fibers was counted on a montage photoprint of the whole nerve, and the diameters of axons and the thickness of the myelin sheath were measured on digitized images. With a portion of nerve as guide, the regeneration is faster than with a vein. However, regeneration after 6 months is at least as good with a venous graft filled with Schwann cells, as assessed by electrophysiological, functional, and histological analysis. The addition of Schwann cells in grafted veins allows the nerve to regenerate through longer gaps than previously described (25 vs 15 mm). In order to assess the quality of nerve regeneration, functional, electrophysiological, and histological analysis are complementary.
Injuries to peripheral nerves innervating a limb cause paralysis, and can necessitate amputation. The inability of the nerves to regenerate spontaneously and the limitations of autograft procedures led to the development of treatments involving insertion of the nerve ends into prosthetic tubular devices. Previous work showed that 'entubulation' of the nerve ends in a silicone tube containing a specific porous, resorbable collagen-GAG (CG) copolymer, serving as an analog of extracellular matrix, improved regeneration compared to an empty silicone tube. However, long-term treatment with silicone tubes produced constriction that caused partial degradation of the regenerated axons; for this and other reasons, implementation of a nondegradable tube may require a second surgical procedure for removal. In this study the silicone tube was replaced with porous and non-porous collagen tubes in order to produce fully degradable devices. CG-filled collagen tubes and controls (CG-filled silicone tubes and empty collagen and silicone tubes) were implanted in a 10-mm gap in the rat sciatic nerve, with three rats in each group. The regeneration was evaluated after six weeks using light microscope images of cross sections of the nerve that were digitized and analyzed. Histograms of the diameters of the axons were generated and compared. The cellular response to the implanted biomaterials was assessed histologically, and immunohistochemistry was performed using an antibody to alpha-smooth muscle actin in order to determine the presence of myofibroblasts (contractile cells). Axonal regrowth was comparable in porous collagen, non-porous collagen, and silicone tubes filled with a CG matrix. These results support the implementation of a degradable collagen tube in place of a silicone device. Confirming earlier work, regeneration through the silicone and collagen tubes was enhanced by the CG copolymer, compared to empty tubes. A notable finding was a continuous layer of myofibroblasts on the surfaces of all of the six silicone tube prostheses, but on the inner surface of only one of six collagen tubes (Fisher's exact tests; P < 0.01). This is the first report of contractile capsules around silicone tubes, and supports the use of degradable collagen tubes in peripheral nerve regeneration. Macrophages were found bordering both the silicone and collagen tubes, and in the case of the collagen tubes, appeared to be participating in the regulation of the tubes.
Cellular channels during development and after peripheral nerve injury are thought to provide guidance cues to growing axons. In tissue culture where these cues are absent, neurites from dorsal root ganglion neurons grow with a radial distribution. To induce directional axonal growth and to enhance the rate of axonal growth after injury, we have designed microfilaments of poly(L-lactide). We demonstrate that dorsal root ganglia grown on these filaments in vitro extend longitudinally oriented neurites in a manner similar to native peripheral nerves. The extent of neurite growth was significantly higher on laminin-coated filaments compared with uncoated and poly-L-lysine-coated filaments. As high as 5.8 +/- 0.2 mm growth was observed on laminin-coated filaments compared with 2.0 +/- 0.2 mm on uncoated and 2.2 +/- 0.3 mm on poly-L-lysine-coated filaments within 8 days. Schwann cells were found to grow on all types of filaments. They were, however, absent in the leading edges of growth on laminin-coated filaments. Photolysis of Schwann cells caused a significant reduction in the neurite length on all types of filaments. Laminin-coated filaments, however, induced significantly longer neurites compared with uncoated and/or poly-L-lysine-coated filaments even in the absence of Schwann cells. Our results suggest that laminin-coated poly(L-lactide) filaments are suitable for inducing directional and enhanced axonal growth. Implants designed by arranging these microfilaments into bundles should aid regenerating axons by providing guidance cues and channels to organize matrix deposition, cell migration, axon growth, and improve functional recovery.
Silicone rubber (polydimethyl siloxane) tubes are used clinically in peripheral nerve reconstruction. A disadvantage of this procedure is that the material often has to be removed owing to its mechanical properties. The aim of our study was to investigate the healing of reconstructed sensory nerves tubulized by silicone rubber in an animal model. In our experiments, we reconstructed the saphenous nerves in 27 rabbits. In series 1 (n = 12), silicone rubber tubes were slid over a nerve suture without a gap. In series 2 (n = 12), silicone rubber tubes were slid over a 10-mm nerve gap. In series 3 (n = 12), conventional suturing was performed in the collateral saphenous nerves of the animals of the series 1. Epineurial suturing was performed. Three other collateral nonoperated saphenous nerves served as controls. The healing was studied after 3, 6, and 12 months. Morphometric analysis of the regenerating axons was performed by using our new method for quantification of nerve fibers in cross sections stained by immunohistochemistry and using confocal laser scanning microscopy. Data analysis was carried out using a software program especially developed for this purpose. Our results showed in the silicone procedures that at 12 months significantly fewer axons per fascicle area were present compared with conventional suturing. However, mean axon diameters in the distal nerve stump of the silicone procedures did not differ significantly compared with the conventional suturing procedure. The ratio of total axon area to total fascicle area in the distal nerve stumps of the silicone procedure without gap was significantly smaller compared with the conventionally sutured nerve. The percentage outgrowing axons from the proximal nerve stump into the distal one in the silicone rubber procedure without gap was 57%. This was significantly higher than in the silicone rubber procedure with 10-mm gap (48%). However, in conventional suturing, the percentage of outgrowing axons (99%) was significantly higher than in both tubulization procedures. It appeared that tubulization by silicone rubber of sutured nerves without gap did not enhance axon regeneration. Conventional suturing gave significantly better results. If a gap was present, the use of a silicone rubber tube was preferable to non-suturing.
The epineural repair technique, which is the gold standard of peripheral nerve injuries, is still far from being ideal. The purpose of this study was to investigate the effects of the turnover epineural sheath tube (TEST) when used over the primary nerve repair site to improve nerve regeneration. Twenty-five Wistar rats were divided into three groups and were operated. In the sham control group, the sciatic nerve was dissected from the sciatic notch to its bifurcation and was left intact. In the primary epineural repair group an incision was made on the nerve and it was repaired using six epineural sutures. In the TEST group, after the incision was made the nerve ends were approximated with two epineural sutures. A proximal circular epineural incision was then made to enable the epineurium to be turned and slid over the repair site. Functional recovery was evaluated by walking tract analysis, and the sciatic functional index was calculated. Histomorphometric studies of the sciatic nerves and gastrocnemius muscles were also performed 3 months postoperatively. Three months postoperatively, functional analysis and nerve and muscle histomorphometric studies revealed similar results in the primary repair and TEST groups. There was no significant difference (p > 0.05) between the results of the TEST and the primary nerve repair groups. However, during the microscopic examination, a decrease in both foreign material reaction and an inflammatory response with less fibrosis were observed in the TEST group. The TEST has a nerve-healing property similar to primary epineural repair, with the advantage of a reduced number of sutures, which decreases the fibrosis around the repair site. The TEST is an alternative treatment modality among other techniques, especially for polyfascicular peripheral nerves.
The management of peripheral nerve injury continues to be a major clinical challenge. The most widely used technique for bridging defects in peripheral nerves is the use of autologous nerve grafts. This technique, however, necessitates a donor nerve and corresponding deficit. Many alternative techniques have thus been developed. The use of skeletal muscle tissue as graft material for nerve repair is one example. The rationale regarding the use of the skeletal muscle tissue technique is the availability of a longitudinally oriented basal lamina and extracellular matrix components that direct and enhance regenerating nerve fibers. These factors provide superiority over other bridging methods as vein grafts or (non)degradable nerve conduits. The main disadvantages of this technique are the risk that nerve fibers can grow out of the muscle tissue during nerve regeneration, and that a donor site is necessary to harvest the muscle tissue. Despite publications on nerve conduits as an alternative for peripheral nerve repair, autologous nerve grafting is still the standard care for treatment of a nerve gap in the clinical situation; however, the use of the skeletal muscle tissue technique can be added to the surgeon's arsenal of peripheral nerve repair tools, especially for bridging short nerve defects or when traditional nerve autografts cannot be employed. This technique has been investigated both experimentally and clinically and, in this article, an overview of the literature on skeletal muscle grafts for bridging peripheral nerve defects is presented.
A number of evaluation methods that are currently used to compare peripheral nerve regeneration with alternative repair methods and to judge the outcome of a new paradigm were hypothesized to lack resolving power. This would too often lead to the conclusion that the outcome of a new paradigm could not be discerned from the outcome of the current gold standard, the autograft. As a consequence, the new paradigm would incorrectly be judged as successful.
An overview of the methods that were used to evaluate peripheral nerve regeneration after grafting of the rat sciatic nerve was prepared. All articles that were published between January 1975 and December 2004 and concerned grafting of the rat sciatic nerve (minimum graft length 5 mm) and in which the experimental method was compared with an untreated or another grafted nerve were included. The author scored the presence of statistically significant differences between paradigms.
Evaluation of nerve fiber count, nerve fiber density, N-ratio, nerve histological success ratio, compound muscle action potential, muscle weight, and muscle tetanic force are methods that were demonstrated to have resolving power.
A number of evaluation methods are not suitable to demonstrate a significant difference between experimental paradigms in peripheral nerve regeneration. It is preferable to apply a combination of evaluation methods with resolving power to evaluate nerve regeneration properly.
Lewis rats (RT1(1] were the recipients of 3-cm nerve grafts from syngeneic Lewis donors or allogeneic ACI (RT1a) donors. Microneurosurgical repair of the nerve graft to the transected sciatic nerve of the recipient animal was performed with 10-0 epineurial sutures. Recipients were randomly allocated to cyclosporin A (CsA) immunosuppressed or untreated groups. Cyclosporin A was administered in the minimal effective dosage to prevent nerve allograft rejection across this major histocompatibility disparity (5 mg/kg per day). Nerve regeneration across the nerve grafts was assessed by sciatic function index (SFI) and toe spread index (TSI) determinations serially and by electrophysiologic, histologic, and morphologic assessments 14 weeks after engraftment. Sciatic nerve regeneration across allogeneic nerve grafts in cyclosporin A immunosuppressed recipients was significantly superior compared to the untreated controls (p less than 0.008) and not significantly different from that across the syngeneic control animals.
Internal neurolysis (intraneural neurolysis) remains controversial. While it seems that operating within a nerve might be detrimental, because of the possibility of creating increased scarring, there are both clinical and experimental reports suggesting that where significant intraneural fibrosis already exists, e.g. in chronic compression neuropathies, internal neurolysis improves nerve function. It is anticipated that the number of surgeons using internal neurolysis as a therapeutic adjunct will be increasing. Although the techniques for teaching microvascular anastomoses have been extensively worked out, a technique for teaching microsurgical intraneural neurolysis has not been described. The goal of this paper is to present an acceptable animal model for practicing the techniques of intraneural neurolysis in the laboratory rather than in the operating room.
Cross-sectional areas at different levels, number of axons, maximal diameters, and number and maximal diameters of vessels were measured comparing autologous transplants with synthetic implants and nonlesion controls in a rat nerve regeneration model. The corresponding electrophysiologic data have been reported earlier in this journal. Although similar in many aspects, transplants led to the overall more reliable and slightly superior results, still lacking a substantial percentage of numerical qualities found in normal nerve, at least within the 3-month regeneration in this study.
This article describes a model of chronic nerve compression in the rat. The sciatic nerve of adult male Sprague Dawley rats was banded with a 1-cm Silastic tube for varying periods of time. Morphometric analysis, electrodiagnostic studies, and histological evaluation were carried out 3, 5, 8, and 12 months after banding. Histological evaluation at 3 months was normal. At 5 months perineurial thickening was demonstrated. In the periphery of the fascicles, segmental demyelination was noted; central fibers appeared normal. At 8 months there was further epineurial and perineurial thickening. Marked thinning of the myelin was noted in all fibers and evidence of Wallerian degeneration was apparent. Progressive connective tissue and nerve fiber changes were noted at 12 months. Nerve conduction studies after 3 months of compression demonstrated an increase in conduction velocity compared to the normal unbanded control nerves. Progressive slowing of conduction velocity was noted from 5 through 12 months.
These experiments present quantitative data concerning peripheral nerve regeneration in vivo. We used entubulation repair as a model to compare two different types of tubular prostheses, one nonbiodegradable and the other biodegradable. We modified the microenvironment of the regenerating axons within the tubular prostheses by adding a laminin-containing gel to the interior of the tube at the time of initial implantation. The data demonstrate that specific manipulations to the microenvironment of regenerating peripheral axons have quantitative effects on the rate and extent of nerve regeneration. Such effects were dependent on the composition of the tubular prosthesis and varied according to the survival time of the animals. For instance, the laminin gel within the biodegradable tubes enhanced nerve regeneration at 2 weeks but was inhibitory at 6 weeks. Furthermore, such manipulations may have different effects on the number of myelinated axons found within the regenerating nerve cable versus the number of primary motor and sensory neurons giving rise to such axons. We concluded that: the presence of a laminin-containing gel significantly increased the initial rate at which axons from primary sensory and motor neurons cross a transection site; an initial delay in axonal outgrowth at early time points did not necessarily predict diminished outgrowth at later times; and because of the potential for axonal branching the number of myelinated axons found in the midportion of a tubular prosthesis did not always correlate with the number of primary motor and sensory neurons which gave rise to those axons.
The sciatic nerve of adult mice was transected and proximal and distal nerve stumps were sutured into a nontoxic bioresorbable nerve guide. Nerve guide lumens were either empty or filled with a gel containing 80% laminin and additional extracellular matrix components. Two weeks later cells in the L3 through L5 dorsal root ganglia and the ventral horn of the spinal cord were retrogradely filled with horseradish peroxidase. All animals with the laminin-containing gel but none with empty nerve guides displayed labeled cells. This suggests that the laminin-containing gel significantly hastened axonal regeneration in vivo.
An in vivo preparation is presented to study the rate and time course of motor and sensory axonal regeneration. The cut ends of a transected sciatic nerve were inserted into each end of a 5-6 mm non-toxic and bioresorbable nerve guide tube to create a 4 mm nerve gap in adult mice. Subsequently, cell bodies in the ventral spinal cord and L3-L5 dorsal root ganglia that had regenerated axons across the gap were retrogradely labeled with horseradish peroxidase (HRP). The HRP was applied 3 mm distal to the nerve guide and was accessible only to axons that had regenerated through the nerve guide. Labeled cells were counted in 40 micron serial sections at 2, 4 and 6 weeks after initial nerve transection. The results indicate a significant increase in the number of labeled motor and sensory cell bodies over time. By 6 weeks after transection, approximately two thirds as many ventral horn motor cells and one third as many dorsal root ganglion sensory cells were labeled as in control non-transected animals. These data serve as a baseline to compare differential effects of additives to the nerve guide lumen in terms of sensory and motor neuron response.
Peripheral compression neuropathy is a common clinical entity but little human nerve material has been available for study. It has been difficult to develop an experimental model of chronic nerve compression which is reliable and reproducible, making it difficult to assess the various treatment modalities currently in use to manage this problem. In a recent study using a rat model, connective tissue and nerve fiber changes associated with chronic nerve compression were described by the authors. The present study expands this same model of chronic nerve compression to the multifascicular median nerve of the cynomolgus monkey, using this model to test whether or not current surgical treatment modalities for nerve entrapment will alter the course of chronic nerve compression. Using histologic and morphometric parameters, there did not appear to be a difference between nerves treated by decompression alone or by decompression and internal neurolysis. Total number of nerve fibers remained constant, as did axon size, but a demyelinating process was demonstrated which is a significant component of chronic nerve compression. Although the small number of experimental animals (7) makes precise evaluation of the clinical modalities impossible, the authors expect that further study of the multifascicular median nerve of the cynomolgus monkey will prove to be a useful source of future experimental evidence and will help to interpret the diverse therapeutic and operative techniques currently in use.
Defects in a sectioned tibial nerve were bridged by a new method using a polyglactin mesh-tube and compared with conventional nerve grafting in the rabbit. The capability of healing was evaluated by morphometrical observations and repeated EMG-recordings. Only minor differences between the two different techniques were observed and the possible advantage of the polyglactin method is discussed.
This study was performed to determine whether vein grafts might serve as a conduit for nerve regeneration. A 1 cm segment of sciatic nerve was removed bilaterally in 12 Sprague-Dawley rats. On one side the gap was not repaired, and on the other side a segment of femoral vein was used to bridge the nerve gap. Nerve conduction studies and necropsies were performed at intervals. Reconstitution of nerve trunk continuity and healing of plantar ulcers occurred only in the vein-grafted side. Histologic examination revealed orderly growth of nerve fibers within the lumen of the vein grafts as early as 1 month after repair. Most regenerating nerve fibers passed through the proximal junction in an orderly pattern and reached the distal stumps within 2 months after repair. Results of nerve conduction study at 4 months after operation demonstrated restoration of conduction through the vein-grafted sciatic nerves with muscle reinnervation. Nearly normal muscle fibers in the gastrocnemius on the repaired side were confirmed at necropsy. This study demonstrated that autogenous vein grafts can serve as a conduit for nerve regeneration in rodents.
The range of growth-promoting influences from a distal nerve stump on a regenerating proximal stump was determined using an experimental system in which a gap between cross-anastomosed rat sciatic nerves was encased by a cylindrical silicone chamber. Two arrangements were examined after 1 month in situ: A proximal-distal (PD) system in which both proximal and distal stumps were introduced into the ends of the chamber, and a proximal-open (PO) system in which the distal stump was omitted. When the gap was 6 mm long, a regenerated nerve extended all the way through the chamber in both the PD and PO systems. When the gap was increased to 10 mm, a similar regrowth occurred in the PD chamber, whereas in the PO chamber proximal regrowth was partial or nonexistent. When the gap was increased to 15 mm, no regeneration occurred, even in the presence of the distal stump. These observations confirm that the distal stump influences proximal regeneration and indicate that this influence can act only over a limited distance or volume. Such an influence could consist of humoral agents which support nerve growth and/or outgrowth from the distal stump.
We have compared the anatomic and functional regeneration of a transected sciatic nerve following regrowth from its proximal stump through either preformed empty mesothelial chambers or autologous nerve grafts bridging a 10 mm gap. Within the mesothelial chambers an organized multifascicular nerve trunk forms between the proximal and distal stumps. After 3 months, distal segment cross sections from the mesothelial chamber and nerve graft groups did not differ with respect to axonal density or distribution of axonal diameters. Mean conduction velocities across the gaps were also similar, although the nerve graft group had a wider distribution of velocities. Little or no regeneration was evident when the gap between the nerve stumps was left empty. These results suggest that if the regrowing proximal stump is in an appropriate environment, it can form a well organized and oriented nerve trunk. In the mesothelial chambers, the regenerating nerve is surrounded by a loose cellular stroma and a small amount of interstitial fluid, which was found to contain trophic activity for cultured rodent sensory neurons. Such factors may also support nerve regeneration in vivo.
In a two-stage procedure the pseudosynovial sheath, formed around a silicone rubber rod placed in the back of rats, was used as a free "tube-graft" to bridge freshly cut gaps of 12 mm length in the sciatic nerve. The tube was kept open by a thin metal spiral, originally implanted around the silicone rubber rod. In this model the regenerating nerve fibers grew into an "open" space formed inside the pseudosynovial tube. The tissue formed in the tube was analyzed after 3 months by light and electron microscopy. Within the tube a new nerve trunk was formed, comprising closely packed myelinated and nonmyelinated fibers organized in fascilcles. The fascicles were surrounded by regenerated perineurim, and the new nerve was surrounded by an epineurium-like sheath. An electromyogram recorded from the flexor muscles of the foot confirmed motor reinnervation. The findings are discussed in view of current concepts of nerve regeneration.
Mackinnon nerve compression 13 Mackinnon SE. model for chronic 194 Bain JR. Mackinnon Peripheral nerve allograft: allograftsin rats immunosuppressed constr An in vivo model to quantify peripheralnerve regeneration
- Ii Klinedg
- Kahn
- Schneider
- Dellonal
- Seiler
- Wa
- R Crosurgicalintraneural
- P Dikkes
II. KlineDG.Kahn Schneider RC (ed): 506-527. 11. O'BrienJP, Mackinnon nerve compression 13. DellonAL, Seiler WA, Jiranek crosurgicalintraneural 1987. 14. Mackinnon SE. model for chronic 194, 1985. 15. Bain JR. Mackinnon Peripheral nerve allograft: allograftsin rats immunosuppressed constr Surg 82:1051-1064, R. Dikkes P. et al.: An in vivo model to quantify peripheralnerve regeneration Brain Res 342:307-315. H. Engkvist0,Hagglund J. et ai.: 'crye tube and nerve graft: An experirnenul 4:276-280,1983
Freidrich H: \'c,'e regeneration in synthetic and autogenous interfascicular gr:?f:s
- H Muller
- K Shibib
- M Modrack
Muller H. Shibib K. Modrack M. Freidrich H: \'c,,'e regeneration in
synthetic and autogenous
interfascicular
gr:?f:s. Exp Neurol 98:
161-169, t987.
An in vivo model to quantify motor and sensory peripheral nerve regeneration using biorcsorbable nerve guide tubes
- I Dasilva
- Cf Madison
- R Dikkes
I. daSilva CF. Madison R. Dikkes P. et al.: An in vivo model to quantify
motor and sensory peripheral nerve regeneration using biorcsorbable
nerve guide tubes. Brain Res 342:307-315. t9:;5.
Surgical repair of acute peripheral nerve injuries: Timing and technique
- Dg Kline
- Ar Hudson
Kline DG. Hudson AR: Surgical repair of acute peripheral nerve injuries: Timing and technique. in Morley TP (ed): Current Controversies in Neurosurgery.
Philadelphia.
W.B. Saunders,
1976. pp
184-197.
The surgery of peripheral nerve injuries
- Ii Kline
- Dg Kahn
II. Kline DG. Kahn EA: The surgery of peripheral nerve injuries. in
Schneider RC (ed): Correlative Neurosurgery,
Tnomas,
1981. pp
506-527.