Use Of Autologous Nerve Grafts Research Articles

Transplantation of peripheral nerve tissueoid based on a decellularized optic nerve scaffold to restore rat hindlimb sensory and movement functions

Peripheral nerve injury (PNI) involving the loss of sensory and movement functions is challenging to repair. Although the gold standard of PNI repair is still the use of autologous nerve grafts, the destruction of the donor side is inevitable. In the present study, peripheral nerve tissueoids (PNTs) composed of a Schwann cell (SC)-based neurotrophin-3 (NT-3) delivery system and a decellularized optic nerve (DON) with naturally oriented channels were engineered to investigate the mechanism of PNTs in nerve regeneration. Proteomic analysis and mRNA sequencing revealed that PNTs have the advantage of promoting nerve regeneration by the three mechanisms of chemotaxis, adhesion and intrinsic mobilisation. The results demonstrated that a local NT-3-enriched pool was constructed by laminin γ3 (LAMC3) in PNTs, creating a niche for the colonization of TrkC-positive SCs, attraction of axons to the defect/graft area, and remyelination. In addition, LAMC3 in PNTs can rapidly promote axon adhesion through integrin aVβ6 and can precisely guide long projecting axons to target tissues. Furthermore, the interactions among the NT-3/TrkC, LAMC3/integrin aVβ6 and the scaffold synergistically activate the PI3K-AKT signalling pathway in damaged neurons, further stimulating the intrinsic regenerative drive within the neurons to ultimately achieve the rapid reinnervation and the improvement of sensory and movement functions in the hindlimb.

Electrospun PCL Nerve Wrap Coated with Graphene Oxide Supports Axonal Growth in a Rat Sciatic Nerve Injury Model.

Background/Objectives: Peripheral nerve injuries (PNIs) are a debilitating problem, resulting in diminished quality of life due to the continued presence of both chronic and acute pain. The current standard of practice for the repair of PNIs larger than 10 mm is the use of autologous nerve grafts. Autologous nerve grafts have limitations that often result in outcomes that are not sufficient to remove motor and sensory impairments. Bio-mimetic nanocomposite scaffolds combined with mesenchymal stem cells (MSCs) represent a promising approach for PNIs. In this study, we investigated the potential of an electrospun wrap of polycaprolactone (PCL) + graphene oxide (GO), with and without xenogeneic human adipose tissue-derived MSCs (hADMSCs) to use as a platform for neural tissue engineering. Methods: We evaluated, in vitro and in vivo, the potential of the nerve wrap in providing support for axonal growth. To establish the rat sciatic nerve defect model, a 10 mm long limiting defect was created in the rat sciatic nerve of 18 Lewis rats. Rats treated with the nanocomposites were compared with autograft-treated defects. Gait, histological, and muscle analyses were performed after sacrifice at 12 weeks post-surgery. Results: Our findings demonstrate that hADMSCs had the potential to transdifferentiate into neural lineage and that the nanocomposite successfully delivered hADMSCs to the injury site. Histologically, we show that the PCL + GO nanocomposite with hADMSCs is comparable to the autologous nerve graft, to support and guide axonal growth. Conclusions: The novel PCL + GO nerve wrap and hADMSCs used in this study provide a foundation on which to build upon and generate future strategies for PNI repair.

Use of acellular dermal matrix in peripheral nerve reconstruction: an experimental study on rat sciatic nerve defect

Background In patients with nerve tissue defects, the use of autologous nerve grafts is the standard method of treatment. Alternatives to autologous, nerve grafts have attracted the attention of reconstructive surgeons. In this study, the results of nerve repairs using acellular dermal matrix (ADM) in an experimental rat sciatic nerve defect model are presented. Methods Thirty-six Sprague-Dawley rats were randomized into 5 groups: Group 1: control group, Group 2: negative control group (n = 6), Group 3: autologous nerve graft group (n = 10), Group 4: donor site entubulated with ADM group (n = 10); and Group 5: nerve graft entubulated with ADM group (n = 10). The animals in each group were evaluated for electrophysiologic functions, gastrocnemius muscle weight and histomorphology on the 3rd and 6th month. Results The compound muscle action potential was observed to be distinctly lower in Groups 3, 4 and 5 in comparison to the control group. In Group 4, the gastrocnemius ratio (GCR) values on the 6th month were statistically significantly lower than the GCR values in Group 3 and Group 5, The histological scores and myelinated axonal counts in Group 5 were statistically significantly higher than the values in Group 3 and Group 4. Conclusion The results of this study showed that wrapping ADM around nerve grafts resulted in better outcomes with respect to nerve healing.

Decellularized sciatic nerve matrix as a biodegradable conduit for peripheral nerve regeneration.

The use of autologous nerve grafts remains the gold standard for treating nerve defects, but current nerve repair techniques are limited by donor tissue availability and morbidity associated with tissue loss. Recently, the use of conduits in nerve injury repair, made possible by tissue engineering, has shown therapeutic potential. We manufactured a biodegradable, collagen-based nerve conduit containing decellularized sciatic nerve matrix and compared this with a silicone conduit for peripheral nerve regeneration using a rat model. The collagen-based conduit contains nerve growth factor, brain-derived neurotrophic factor, and laminin, as demonstrated by enzyme-linked immunosorbent assay. Scanning electron microscopy images showed that the collagen-based conduit had an outer wall to prevent scar tissue infiltration and a porous inner structure to allow axonal growth. Rats that were implanted with the collagen-based conduit to bridge a sciatic nerve defect experienced significantly improved motor and sensory nerve functions and greatly enhanced nerve regeneration compared with rats in the sham control group and the silicone conduit group. Our results suggest that the biodegradable collagen-based nerve conduit is more effective for peripheral nerve regeneration than the silicone conduit.

Cell-free artificial implants of electrospun fibres in a three-dimensional gelatin matrix support sciatic nerve regeneration in vivo.

Surgical repair of larger peripheral nerve lesions requires the use of autologous nerve grafts. At present, clinical alternatives to avoid nerve transplantation consist of empty tubes, which are only suitable for the repair over short distances and have limited success. We developed a cell-free, three-dimensional scaffold for axonal guidance in long-distance nerve repair. Sub-micron scale fibres of biodegradable poly-ε-caprolactone (PCL) and collagen/PCL (c/PCL) blends were incorporated in a gelatin matrix and inserted in collagen tubes. The conduits were tested by replacing 15-mm-long segments of rat sciatic nerves in vivo. Biocompatibility of the implants and nerve regeneration were assessed histologically, with electromyography and with behavioural tests for motor functions. Functional repair was achieved in all animals with autologous transplants, in 12 of 13 rats that received artificial implants with an internal structure and in half of the animals with empty nerve conduits. In rats with implants containing c/PCL fibres, the extent of recovery (compound muscle action potentials, motor functions of the hind limbs) was superior to animals that had received empty implants, but not as good as with autologous nerve transplantation. Schwann cell migration and axonal regeneration were observed in all artificial implants, and muscular atrophy was reduced in comparison with animals that had received no implants. The present design represents a significant step towards cell-free, artificial nerve bridges that can replace autologous nerve transplants in the clinic. Copyright © 2017 John Wiley & Sons, Ltd.

The role of exosomes in peripheral nerve regeneration.

Peripheral nerve injuries remain problematic to treat, with poor functional recovery commonly observed. Injuries resulting in a nerve gap create specific difficulties for axonal regeneration. Approaches to address these difficulties include autologous nerve grafts (which are currently the gold standard treatment) and synthetic conduits, with the latter option being able to be impregnated with Schwann cells or stem cells which provide an appropriate micro-environment for neuronal regeneration to occur. Transplanting stem cells, however, infers additional risk of malignant transformation as well as manufacturing difficulties and ethical concerns, and the use of autologous nerve grafts and Schwann cells requires the sacrifice of a functioning nerve. A new approach utilizing exosomes, secreted extracellular vesicles, could avoid these complications. In this review, we summarize the current literature on exosomes, and suggest how they could help to improve axonal regeneration following peripheral nerve injury.

Nerveninterponate zur Wiederherstellung der erektilen Funktion bei radikalen Beckenoperationen

Iatrogenic cavernous nerve lesions occurring during radical pelvic surgery often lead to irreversible erectile dysfunction. The nerve defects after excision of the neurovascular bundles must be reconstructed by interposition grafting to supply a permissive scaffold for oriented axonal regrowth. The use of autologous nerve grafts for the repair of human cavernous nerves during radical prostatectomy has been controversial regarding the limited success achieved with bilateral nerve grafting. Artificial nerve guides consisting of natural or synthetic materials have been successfully used for bridging peripheral nerve defects. The combination with Schwann cells, neurotrophic factors and extracellular matrix components has been shown to promote cavernous nerve regeneration.

The Use of Degradable Nerve Conduits for Human Nerve Repair: A Review of the Literature

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, has some disadvantages. Many alternative experimental techniques have thus been developed, such as degradable nerve conduits. Degradable nerve guides have been extensively studied in animal experimental studies. However, the repair of human nerves by degradable nerve conduits has been limited to only a few clinical studies. In this paper, an overview of the available international published literature on degradable nerve conduits for bridging human peripheral nerve defects is presented for literature available until 2004. Also, the philosophy on the use of nerve guides and nerve grafts is given.

Use of skeletal muscle tissue in peripheral nerve repair: review of the literature.

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.

Alternatives to autologous nerve grafts.

The use of autologous nerve grafts for bridging defects in nerve continuity requires the sacrifice of healthy nerves. Development of alternatives to autologous nerve grafts is therefore well motivated. Such "bioartificial nerve grafts" can be tissue-engineered on the basis of the use of a stroma/matrix/scaffold acting in concert with cells and neurotrophic factors. Such a scaffold can be of synthetic or biological nature and can be resorbable or non-resorbable. It should act together with Schwann cells which can be pre-cultured or acutely dissociated. Neurotrophic factors, stimulating axonal growth, can be incorporated in the scaffold and can also be supplied by cells which are seeded into the stroma. So far, tissue-engineered nerve conduits have been used mainly for experimental purposes in experimental animals. However, an increasing amount of experience from the clinical use of alternatives to nerve grafts now exists, mainly tubes made of silicone or poly-glycolic acid (PGA), veins, collagen and muscle basal laminae.

Use of Tubes in Peripheral Nerve Repair

The use of tubes as an alternative to primary nerve suture in fresh nerve transections has been introduced as a biologic approach to nerve injuries, creating optimal conditions for axonal regeneration over a short empty space intentionally created between the proximal and distal nerve ends. The idea may seem controversial and has been criticized using the arguments that silicone in itself may create problems like inflammation and the tube may compress the nerve ends. With the use of appropriately sized tubes for bridging a maximum 5-mm gap in human median and ulnar nerves, the authors have found the technique to be useful and persistent at follow-up examinations for up to 4 to 5 years. In addition, from the intellectual point of view, the principle illustrates the concept by which emphasis is placed on the intrinsic healing capacities of the nerve rather than on the technical skill of the surgeon. The thin mesothelial lining found around the silicone tube lacks primary inflammatory signs at follow-up after 1 year, and no signs of compression are seen. It may be an advantage because it allows sliding of the repair site against the surrounding tissues. Tubes made of bioresorbable material may seem ideal, but they may introduce new problems associated with the resorption process in terms of a substantial unrestricted macrophage invasion, fibrosis, and disorganized axonal growth. For an extended nerve defect, the use of autologous nerve grafts is still the gold standard, because no tubular conduit or other conduit has so far proved equal to autologous nerve grafts, at least not for reconstruction of human median and ulnar nerve trunks. Alternatives other than tubes are currently being developed and investigated. For the future, the use of tubes for repair and reconstruction of nerves may have interesting potentials, because such a structure allows several types of tissue engineering. Various matrices containing, for instance, appropriate cells, factors, or other stimulating agents can be introduced in the tube lumen and can also be incorporated in a slow-release form in the walls of the tube and manipulated. Cultured Schwann cells or other cellular components, with or without manipulated production machinery, are probably the cells of choice for introduction in the tubes. Tubes may thus prove to be interesting alternatives to conventional repair techniques for primary repair of nerves and for reconstruction of segmental defects and for neuroma treatment in the future.

The Use of Degradable Nerve Conduits for Human Nerve Repair: A Review of the Literature

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, has some disadvantages. Many alternative experimental techniques have thus been developed, such as degradable nerve conduits. Degradable nerve guides have been extensively studied in animal experimental studies. However, the repair of human nerves by degradable nerve conduits has been limited to only a few clinical studies. In this paper, an overview of the available international published literature on degradable nerve conduits for bridging human peripheral nerve defects is presented for literature available until 2004. Also, the philosophy on the use of nerve guides and nerve grafts is given.

INTERPOSITION OF SURAL NERVE RESTORES FUNCTION OF CAVERNOUS NERVES RESECTED DURING RADICAL PROSTATECTOMY

Purpose The permanent loss of erectile function when both neurovascular bundles are widely resected at radical prostatectomy as well as the successful use of autologous nerve grafts in reconstructive surgery led us to perform bilateral nerve grafts in an effort to restore erectile function in potent patients treated for prostate cancer who underwent radical retropubic prostatectomy and resection of both neurovascular bundles. Materials and Methods Radical retropubic prostatectomy with deliberate resection of both neurovascular bundles was recommended for high grade, locally extensive prostate cancer in 9 select, sexually active men who reported normal erectile function. After the prostate was removed but before vesicourethral anastomosis an autologous sural nerve graft was interposed between the divided ends of the cavernous nerves bilaterally. Erectile function was monitored by patient interview, questionnaire and nocturnal penile tumescence testing after the operation. Results Four to 5 months postoperatively patients noticed slowly improving spontaneous erections, as manifested by mild tumescence regularly every several hours. Nocturnal penile tumescence testing with the RigiScan * * UroHealth Systems, Inc., Laguna Niguel, California. device at 4 to 6 months in 2 cases revealed erections that approached minimal criteria for normalcy. Approximately 14 months after surgery a rigid erection sufficient for penetration and intercourse developed in 1 patient. He described this event as “an erection of substance-hard, not just fluffy.” Conclusions We have developed a technique using sural nerve grafts to restore continuity of the cavernous nerves, which are resected during radical prostatectomy. The early return of spontaneous partial erections in our patients suggests that interposition nerve grafts may enhance the recovery of erectile function when the neurovascular bundles are resected.

Neural repair in facial paralysis: clinical and experimental studies.

Acute facial nerve injuries involving the total facial nerve (n = 202) and its segmental branches (n = 63) were repaired with a variety of neural (n = 225) and myofascial transfer (n = 40). A system for evaluating results based on facial symmetry and tone at rest, recovery of voluntary mimetic activity, synkinesis, and recovery of selective function in discrete facial nerve divisions is presented. The best results were achieved with immediate direct end-to-end neural-epineural anastomotic repairs. The least favorable results were seen with myofascial transpositions and long extratemporal rerouted autologous nerve grafts. A series of tissue culture and animal experiments were used to examine structural changes in neural repair. The requirements for successful motoneuron regeneration, causes of synkinesis and methods for nerve stump coaptation are elucidated. Tubulation experiments demonstrated the need for neurotrophic and neuropromotive factors. Problems associated with the use of autologous nerve grafts are discussed.