Autogenous Nerve Grafts Research Articles

Platelet gel does not improve peripheral nerve regeneration: An electrophysiological, stereological, and electron microscopic study

Although use of platelet gel (PG) for promoting tissue regeneration is a popular approach because of its capacity to accelerate tissue regeneration, to our knowledge, its effects on peripheral nerve have still not been elucidated. Therefore, the aim of this study was to investigate effects of PG on sciatic nerve regeneration using electrophysiology, stereology, and electron microscopy. The study was performed using five groups of rats: sham operated (Sham), collagen tube conduit (CT), collagen tube conduit plus platelet gel (CT + PG), autogenous nerve graft (ANG), and primary repair (PR) groups. Gap length for CT and CT + PG groups is 1 cm. Electrophysiology showed that nerve conduction velocity was not different among experimental groups; the amplitude of compound action potential of PR group was significantly higher than other groups. Examination of the nerves showed that Sham group not only had a larger axon diameter but also a thicker myelin sheath. A higher number of myelinated axon was found in both ANG and PR groups in comparison to Sham, CT, and CT+PG groups. There is no significant difference between morphological quantities of CT+PG and CT group. It was expected that regeneration degree of the nerve fibers of CT+PG group would be better than CT group, which was the control group permitting to disclose the presence of a positive effect of PG on nerve regeneration, but this was not the case. Therefore, our results suggest that PG does not improve axon regeneration after microsurgical reconstruction of a nerve gap by collagen tubes.

Comparison of regeneration results of prefabricated nerve graft, autogenous nerve graft, and vein graft in repair of nerve defects

The purpose of this study was to evaluate the effectivity of prefabricated nerve grafts in the repairing nerve defect and to compare them with the autogenous nerve graft and vein graft. Four groups were created, each containing 10 rats. First, nerve prefabrication was carried out in groups I and II during 8 weeks. For this purpose, jugular vein graft was sutured to the epineural windows on the peroneal and tibial nerve at the right side in an end-to-side fashion. To create neurotrophic stimulus, partial incision was performed on the nerves in group I, and gene therapy was performed by plasmid injecting to the adjacent muscles in group II. At the end of the eighth week, prefabricated nerve grafts, jugular vein, and the axons passing through it were taken. Then, gap was created on the left peroneal nerve in all groups. Defect on the peroneal nerve was repaired by using the prefabricated nerve grafts in groups I and II, the autogenous nerve graft in group III, and the vein in group IV. Assessment of nerve regeneration was performed by using electromyography. Morphological assessment was performed after follow-up period. According to electrophysiological and morphological results, the results of first three groups were similar. There was no statistically significant difference between three groups. Prefabricated nerve graft is as effective as autogenous nerve graft, and it can be used in the repair of nerve defects as autogenous nerve graft as an alternative.

Artificial nerve tubes and their application for repair of peripheral nerve injury: an update of current concepts

Over the last 20 years, an increasing number of research articles have reported on the use of artificial nerve tubes to repair nerve defects. The development of an artificial nerve tube as an alternative to autogenous nerve grafting is currently a focus of interest for peripheral nerve repair. The clinical employment of tubes as an alternative to autogenous nerve grafts is mainly justified by the limited availability of donor tissue for nerve autografts and the related morbidity. Numerous studies indicate that short-distance defects in humans can be successfully treated by implantation of artificial nerve guides. This review provides a brief overview of various preclinical and clinical trials conducted to evaluate the utility of artificial nerve tubes for the regeneration of peripheral nerves. This review is also intended to help update hand surgeons on the rapid advances in tubulization techniques, and to provide them with indications of the various directions toward which future research can proceed. Future studies need to provide us with as much comparative information as possible on the effectiveness of different tubulization techniques, in order to guide the surgeon in choosing the best indications for their optimal clinical employment. Future progress in implant development can be expected from interdisciplinary approaches involving both materials and life sciences, leading to advances in neuro-tissue engineering that will be needed to effectively treat larger nerve defects.

Histomorphometric Characteristics of the Facial Nerve

With the development of microsurgery, autogenous nerve grafting is being used widely in the treatment of the injured facial nerve. To use a donor graft for repair of the facial nerve, fascicular area and fascicular number should be considered in the selection of the donor site. This study demonstrated a detailed morphologic description of the facial nerve, including a microscopic assessment of nerve size and shape, and fascicular number and diameters. 40 embalmed hemi-sectioned head specimens from Korean adult cadavers were dissected to identify the facial nerve branches and nerve samples for histologic examination were cut from the anterior margin of the parotid gland. At the border of the parotid gland, the facial nerve specimens were found to have an average of 11 branches (ranging from 8 to 16). The branches were distributed among the five distinct branches, the buccal branch had the greatest number of branches (3.47), and the zygomatic branch had the largest diameters (0.93㎜), The number of fascicles varied from one to 9 over the course of the nerve, the trunk had the greatest number of fascicles (4.36), and averages indicated a tendency for fascicular numbers to decrease distally, from trunk (4.36) to upper division (3.72) to lower division (3.60) to marginal mandibular branch (2.37). The total fascicular area was averaging 2.72㎟, 1.88㎟, and 1.04㎟ at trunk, upper division, and lower division, respectively. However no significant differences of the fascicular diameter could be shown between five branches. This results of detailed facial nerve microanatomy should help in the treatment of the injured facial nerve.

A Comparison of Polyglycolic Acid Versus Type 1 Collagen Bioabsorbable Nerve Conduits in a Rat Model: An Alternative to Autografting

Severe nerve injury with segmental loss requires nerve graft or conduit repair. We compared 2 synthetic, bioabsorbable nerve conduits with the gold standard of autogenous nerve grafting using histopathologic and neurophysiologic analyses. A 10-mm segment of the sciatic nerve of 45 Sprague-Dawley rats was resected, leaving a gap defect. Three experimental groups were used: 15 coaptations using type I collagen nerve conduits, 15 coaptations using polyglycolic acid (PGA) nerve conduits, and 15 coaptations using the excised segments as autogenous nerve grafts. The contralateral legs were used as unoperated controls. After 15 weeks, nerve regeneration was evaluated by measuring isometric muscle contraction force, axonal counting, wet muscle weights, and histology. Statistically significant differences in the isometric muscle contraction force, axonal counts, and wet muscle weights were found between type I collagen conduit and nerve graft compared to the PGA conduit. Axonal sprouting was less organized and less dense with the PGA conduits when compared to nerve reconstruction with the type I collagen conduits and nerve grafts. Type I collagen conduits and autografts produced comparable results, which were significantly better than PGA conduits. The use of type I collagen conduit is a reliable alternative to nerve grafting for gaps up to 10 mm in length.

Estudo comparativo entre enxerto autógeno e enxerto muscular coberto com tubo de veia autógeno em nervos tibiais de ratos wistar, utilizando o fluoro-gold® como marcador neuronal

Este trabalho teve como objetivo o estudo da regeneração nervosa através da contagem de neurônios comparando duas técnicas cirúrgicas no tratamento da perda de substância nervosa nos membros inferiores em 15 ratos. Inicialmente obteve-se tubo de veia de 12mm de comprimento retirado da jugular externa esquerda. A seguir, opera-se os dois membros inferiores, expondo o nervo tibial de cada lado e ressecando um segmento de 8 mm do nervo, simulando, ao mesmo tempo, a perda de substância e a obtenção do enxerto nervoso autógeno. A reparação da perda de substância do lado esquerdo consistiu numa enxertia convencional simples para a reparação de lesão nervosa por meio de sutura microcirúrgica. A do membro inferior direito foi pela tubulização com 8 mm de enxerto de músculo quadríceps denaturado com nitrogênio líquido coberto com veia jugular. Após quatro meses, os animais foram submetidos à nova cirurgia para exposição dos nervos tibiais ao marcador neuronal Fluoro Gold®. Após 48 horas, foram perfundidos e o segmento medular entre L3 e S1 foi removido e posteriormente cortado em secções de 40 µm. Houve contagem neuronal de todos os cortes e não foram verificadas diferenças estatísticas entre as duas técnicas cirúrgicas.

Nerve Grafting in the Upper Extremity by Using the Microscope and Microscopic Techniques: A Long-Term Follow-Up of 130 Cases

The purpose of the study was to demonstrate that autogenous nerve grafting can give rewarding results providing that certain techniques can be applied. There were 130 cases in all; 70 involved the median nerve, 40 the ulnar nerve, and 20 the radial nerve. There were 85 males and 45 females, ranging in age from 20 to 60 years. The time of the injury to grafting was from 6 months to 5 years. Follow-up ranged from 2 to 15 years. The procedure consisted of exploring the injured peripheral nerve, with excision of neuromas and insertion of autogenous nerve grafts that were taken from the lower extremities. The grafts were approximated to the proximal and distal ends of the injured nerve under the microscope by using fine instruments and microsurgical techniques. Motor recovery for median nerve low lesions, i.e., recovery of the thenar muscles to the M3–M4 level was excellent in 38%, for M2–M3 was good in 40%, and for M1–M2 was fair in 20%. Ulnar nerve motor recovery for intrinsics to level M3–M4 was excellent in 38%; for level M2–M3 was good in 40%; for level M1–M2 was fair in 22%. Motor recovery for radial nerve extensors of the wrist, fingers, and thumb to level M3–M4 was excellent in 38%; for level M2–M3 was good in 38%; for level M1–M2 was fair in 20%. In a large number of patients, this method has considerably improved the function of the extremity. It has provided superior results to those before the use of the microscope and microsurgical instruments. By doing nerve grafting, one avoids excessive mobilization of nerve ends, stretching, suturing under tension, and immobilizing of joints.

The Use of Synthetic Polycaprolactone Filaments with and without Sheath to Bridge a Peripheral Nerve Defect

Although autogenous nerve grafting is the main choice for nerve gap management, the use of synthetic nerve tube to bridge a short nerve gap is still a promising alternative for nerve repair. Polycaprolactone (PCL) filaments (30-50 in number) was used as a nerve guide in this study because of good biocompatibility, high permeability as well as low cost. Thirty Sprague-Dawley rats were divided into four groups in this study: group 1, the PCL filaments enveloped by the full sheath; group 2, the PCL filaments held together with autogenous vein grafts at both ends; group3, the PCL filaments held together with a sheath cuff at each end; group 4, the control group, 10 mm in length autogenous nerve graft. Right sciatic nerve was used as the experimental model. Soleus and tibialis anterior muscle's action potentials, muscle contractility test, and histology studies were used for result assessment after six months regeneration period. The results showed that the presence of a sheath around the filament column was the worst. The regenerating nerve fibers most grew along the outer border of the filaments column and very few in the inter-filament space. A nerve guide of PCL filaments without sheath and containing only a few filaments as the supporting frame seems to be the most advantageous for encouraging nerve regeneration. A modified advice with coiling of the PCL sheath instead of a full sheath is prospective to improve the functional outcome.

Radial Sensory Neurotization of the Thumb and Index Finger for Prehension After Proximal Median and Ulnar Nerve Injuries

Proximal median nerve injuries are functionally disabling, secondary to both motor and sensory deficits. Reestablishment of sensation relies on slow axonal regeneration originating from the site of injury after either primary nerve repair or the use of autogenous nerve grafts. This regeneration can take 2 or more years to restore sensation to the hand, depending on injury location. Distal sensory nerve transfers shorten the recovery time by decreasing the required regeneration distance. The authors present two case reports of patients with proximal median nerve injury, who underwent radial sensory nerve transfers to the ulnar digital nerve of the thumb and the radial digital nerve of the index finger. Protective sensation returned to the index and thumb fingertips at 3 months. By 6 months, both patients attained sufficient sensation to permit active lateral key pinch. At 9 months, each patient had moving sensation; and by 14 months, each patient attained proper localization. Successful digital nerve transfers of the dorsal radial sensory nerves in patients with high proximal median nerve injuries return sensation faster than traditional median nerve repairs. Use of this technique will significantly reduce the insensate time in patients with this unfortunate injury.

A Practical Approach to Nerve Grafting in the Upper Extremity

In this era of tissue bioengineering an autogenous nerve graft may be considered the ultimate biocompatible, resorbable nerve conduit, with a basil lamina, preformed guidance channels, a reserve of viable Schwann cells, and nerve growth factors. In addition, it is capable of developing an intrinsic circulation. The nerve graft provides a regenerating axon with a means for passage to the distal nerve stump, while protecting it from the surrounding environment. There is no foreign body reaction and no graft-versus-host response. An enterprising biotechnology company undoubtedly would have no difficulty marketing this product. The results obtained with nerve autografts constitute the gold standard by which nerve conduits are designed and measured. Despite this seemingly utopian picture, the donor site morbidity and the limitations of nerve grafting have led to a search for alternate methods. This search has been addressed eloquently by Strauch and Chui and their coauthors elsewhere in this issue. This article focuses on the ways in which the nerve responds to injury and how it regenerates, followed by some practical considerations for autologous nerve grafting.

Nerve repair by means of tubulization: Literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair

Nerve repair is usually accomplished by direct suture when the two stumps can be approximated without tension. In the presence of a nerve defect, the placement of an autologous nerve graft is the current gold standard for nerve restoration. However, over the last 20 years, an increasing number of research articles reported on the use of non-nervous tubes (tubulization) for repairing nerve defects. The clinical employment of tubes (both biological and synthetic) as an alternative to autogenous nerve grafts is mainly justified by the limited availability of donor tissue for nerve autografts and the related morbidity. In addition, tubulization was proposed as an alternative to direct nerve sutures in order to create optimal conditions for nerve regeneration over the short empty space intentionally left between two nerve stumps. This paper outlines recent important advances in this field. Different tubulization techniques proposed so far are described, focusing in particular on studies that reported on the employment of tubes with patients. Our personal clinical experience on tubulization repair of sensory nerve lesions (digital nerves), using both biological and synthetic tubes, is presented, and the clinical results are compared. In our case series, both types of tubes led to good clinical results. Finally, we speculate about the prospects in the clinical application of tubulization for peripheral nerve repair.

Diagnosis and management of trigeminal nerve disorders

Diagnosis and management of trigeminal nerve disorders

Nerve conduits for nerve reconstruction

Although autogenous nerve grafting remains the gold standard for repair of peripheral nerve defects, the use of various conduits can be a substitute provided these conduits meet the above-mentioned prerequisites. For the moment, autogenous vein grafts or denatured muscle grafts can be used to bridge short defects, especially in distal sensory nerves. Incorporation of muscle into a vein graft expands its application to longer defects in bigger nerves. PGA conduits have also been clinically proven to be reliable in reconstruction of digital nerve defects. Although nonabsorbable conduits cause irritation and nerve compression that necessitates secondary surgery removal, silicone tubes or Goretex tubes can be used in selected cases until absorbable conduits large enough for major peripheral nerves are available. To date, 3 cm seems to be the barrier for conduits. Incorporation of trophic factors and Schwann cells into the conduits will make their way into the clinic if problems like controlled release of trophic factors, obtaining and sustenance of an appropriate number of viable Schwann cells, are solved.

Autogenous venous graft with one-stage prepared Schwann cells as a conduit for repair of long segmental nerve defects.

The use of autogenous venous graft with intraluminal injection of Schwann cells to enhance nerve regeneration of long segmental nerve defects was evaluated in a rabbit tibial nerve-repair model. Schwann cells were isolated from the excised rabbit tibial nerve by using the polylysine differential adhesion method. The cultured cells were identified by immunocytochemical labeling for S-100 protein. Tibial nerve defects in 4-cm segments were created in 24 animals, which were then divided into three groups. In Group 1, the tibial nerve defect was repaired with interposition vein graft alone; in Group 2, the nerve defect was repaired with a vein graft with intraluminal injection of Schwann-cell suspension; in Group 3, the nerve defect was repaired by autogenous nerve graft alone. At 2 months postoperatively, electrophysiologic evaluation showed that an evoked muscle action potential was recorded for the animals in Group 2, with vein grafting plus Schwann cells, and for those in Group 3, with autogenous nerve grafting, but not for those in Group 1, where vein grafting alone was used. The average motor nerve conduction velocity in the group with vein grafting and Schwann cells was 3.4 +/- 1.5 m/sec, which was slower than the nerve grafting group (7.8 +/- 1.8 m/sec). Histologic analysis confirmed there was formation of new nerve fascicles with myelination in the vein graft filled with Schwann cells. No nerve regrowth was found in the vein grafts without Schwann cells. These results suggested that isolated Schwann cells are able to survive in a vein graft, and that the vein graft with intraluminal seeded Schwann cells could be an alternative for repairing injured nerves with long gaps.

Prefabrication of a free peripheral nerve graft following implantation on an arteriovenous pedicle.

Extensive nerve injuries frequently necessitate the use of long autografts, and sources of expendable donor nerves are limited. It is for these cases that nerve transplantation would have its greatest potential. However, regeneration in the rejected allograft fails because of a lack of the positive neurotropic and neurotrophic influences physiologically provided by viable Schwann cells. This report aims to show the feasibility of vascularization of the peripheral nerve by prefabrication. The study was designed to vascularize an autogenous nerve graft segment by using an arteriovenous bundle in the rabbit. A 3.5-cm segment of sciatic nerve was harvested and implanted in between the femoral vessels, and was isolated from secondary revascularization by a custom-made tube. A peripheral nerve graft was prefabricated by implantation on the vascular pedicle, and neovascularization was evaluated by microangiography and histology. The graft exhibited early neovascularization on day 2, and numerous new capillaries were noted to restore primarily perineurial blood flow on day 7, then all along the graft on day 14. The viability of the Schwann cells was preserved, and the structural integrity of the graft was maintained. This is a preliminary report on secondary vascularization of a segment of an autogenous nerve to maintain the viability of Schwann cells and the integrity of the conduit. In the future, with the concomitant use of host immunosuppression or with more advanced pre-treatment methods, nerve allografts could be revascularized by vascular bundles. The current tempo of medical research will hopefully enable the use of fresh nerve allografts that are rendered less immunogenic by more refined techniques.

Bioactive poly( l-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration

This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously tested poly( l-lactic acid) (PLLA) conduits by incorporating them with allogeneic Schwann cells (SCs). The SCs were harvested, cultured to obtain confluent monolayers and two concentrations (1×10 4 and 1×10 6 SC/ml) were combined with a collagen matrix (Vitrogen) and injected into the PLLA conduits. The conduits were then implanted into a 12 mm right sciatic nerve defect in rats. Three control groups were used: isografts, PLLA conduits filled with collagen alone and empty silicone tubes. The sciatic functional index (SFI) was calculated monthly through four months. At the end of second and fourth months, the gastrocnemius muscle was harvested and weighed for comparison and the graft/conduit and distal nerve were harvested for histomorphologic analysis. The mean SFI demonstrated no group differences from isograft control. By four months, there was no significant difference in gastrocnemius muscle weight between the experimental groups compared to isograft controls. At four months, the distal nerve demonstrated a statistically lower number of axons/mm 2 for the high and low SC density groups and collagen control. The nerve fiber density was significantly lower in all of the groups compared to isograft controls by four months. The development of a “bioactive” nerve conduit using tissue engineering to replace autogenous nerve grafts offers a potential approach to improved patient care. Although equivalent nerve regeneration to autografts was not achieved, this study provides promising results for further investigation.

Gene expression of transforming growth factor beta isoforms in interposition nerve grafting.

Scar production and neuroma formation at nerve graft coaptation sites may limit axonal regeneration and impair functional outcome. Transforming growth factor beta (TGF-beta) is a family of growth factors that is involved in scar formation, wound healing, and nerve regeneration. Fifteen adult Sprague-Dawley rats underwent autogenous nerve grafting. The nerve grafts were analyzed by in situ hybridization to determine the temporal and spatial expression of TGF-beta1 and TGF-beta3 messenger RNA (mRNA). The grafted nerves showed increased expression of TGF-beta1 and TGF-beta3 mRNA in the nerve and the surrounding connective tissue during the first postoperative week. These data suggest that modulation of TGF-beta levels in the first postoperative week may be effective in helping to control scar formation and improve nerve regeneration.

In reply:

We thank Drs Meek and Coert for their comments and critical review of our study. They have an obvious interest in the use of conduits to repair peripheral nerve gap defects. The purpose of our investigation was simply to introduce a potential alternative technique for repairing nerve gap defects; therefore, the review of the use of conduits was intentionally limited for one fundamental reason. There is an evolving and interesting body of literature that investigates various conduits, with and without growth factors and Schwann cells, but in the clinical setting the use of autogenous nerve grafts to repair nerve gap defects is the current standard.1 A number of studies from Dr Meek's laboratory using a rat model in addition to a lone clinical study that does not evaluate motor function are referenced. We do not dispute the results of these investigations; however, all must agree that the use of artificial conduits has not displaced autogenous nerve grafting and therefore we stand by our comments. Clearly, the ideal nerve conduit will include Schwann cells and growth factors in a manner that reproduces autogenous nerve grafts. There have been no studies of nerve conduits crossing joints and bridging gaps of greater than 4.0 cm, situations in which autogenous grafts are routinely used. In the clinical setting there have been problems with nerve conduits eroding through skin, which have not reported for autogenous nerve grafts.

Nerve Harvesting Procedures

Autogenous nerve grafts currently set the standard for reconstruction of motor and sensory nerve injuries that cannot be repaired by mobilization, advancement, and approximation, and suturing without tension. Donor nerves such as the GAN and SN are easily accessible and frequently used in maxillofacial microneurosurgery. Other nerves (MACN, LCNF, LTN) may serve well in special nerve reconstruction situations. In the future, availability of biodegradable nerve conduits with neurotrophic factors may render obsolete the reconstruction of the short-span nerve gap (< 3 cm) by autogenous nerve grafts.

Facial nerve repair with expanded polytetrafluoroethylene and collagen conduits: An experimental study in the rabbit

Purpose: This study evaluated autogenous nerve grafts and expanded polytetrafluoroethylene (e-PTFE) and collagen tubes as conduits for the repair of continuity defects in the facial nerve of rabbits. Materials and Methods: The buccal division of 24 facial nerves was isolated, transected, and separated 10 mm. The gap between the 2 nerve ends was then repaired with an autologous nerve graft or an e-PTFE or collagen conduit. Fifteen days and 1, 2, and 4 months after the procedure, the animals were subjected to electrophysiologic tests, killed, and the nerves were removed for histologic examination. Results: At 15 days postsurgery, no regeneration was observed through the e-PTFE and collagen tubes or accross the autologous nerve grafts at the midpoint of the specimens. However, regeneration across the chambers and autologous nerve grafts was seen in the following 4 months, although the number of axons regenerated was small. Conclusions: The results of the study indicate that e-PTFE and collagen tubing may be effective in the repair of continuity defects in peripheral nerves. However, further research will be necessary for generalization of this procedure. © 2000 American Association of Oral and Maxillofacial Surgeons