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Autogenous vein graft as conduit for nerve regeneration
Abstract
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.
... Peripheral nerve injury repair is challenging in reconstructive surgery. Autogenous nerve grafts are the gold standard for repairing peripheral nerve defects; however, there are some associated problems, such as loss of function and sensation in the donor area and mismatched nerve tube diameter (Chiu et al., 1982;Rinkel et al., 2013;Wang et al., 2018). Artificial nerve guide conduits can also be used to repair nerve defects (Griffin et al., 2013;Lin et al., 2017;Sun et al., 2018;Quan et al., 2019). ...
... Moreover, the outer membrane of veins is rich in collagen, and the middle membrane is rich in laminin, which can promote nerve regeneration (Wang et al., 1993;Tseng et al., 2003). Chiu et al. (1982) showed that autogenous vein grafts can be used as effective conduits for nerve regeneration. Since then, a series of clinical studies have demonstrated that autologous vein grafts can be used to repair peripheral nerves, with satisfactory results (Chiu and Strauch, 1990;Tang et al., 1993). ...
... Vein tubes have been widely used as nerve conduits for nerve regeneration for many years (Chiu et al., 1982;Manoli et al., 2014;Eren et al., 2018). Veins are nonimmunogenic, with less pronounced inflammatory responses, and can be obtained in a variety of sizes. ...
Veins are easy to obtain, have low immunogenicity, and induce a relatively weak inflammatory response. Therefore, veins have the potential to be used as conduits for nerve regeneration. However, because of the presence of venous valves and the great elasticity of the venous wall, the vein is not conducive to nerve regeneration. In this study, a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats. Compared with rats given the vein graft alone, rats given the tissue engineered nerve graft had an improved sciatic static index, and a higher amplitude and shorter latency of compound muscle action potentials. Furthermore, rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone. However, the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation. In summary, although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects, it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects. This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2016-x9-07) on September 7, 2016.
... short nerve gaps experimentally in the rat(Chiu, Janecka et al. 1982) and in rabbit(Li and Cao 2000). Vein grafts can be harvested in different sizes and lengths and so they can be used for repair of nerves with good matching whatever the caliber of the nerve trunk or the length of the nerve gap to be reconstructed. ...
... Results to date are encouraging(Zhang, Blain et al. 2002), with good axonal regeneration could been demonstrated through autologous vein grafts of up to 6 cm in a rabbit model(Strauch, Rodriguez et al. 2001). In rat experimental model, the most commonly used vein is the femoral vein graft(Chiu, Janecka et al. 1982;Di Benedetto, Zura et al. 1998), however, the jugular vein was found to be superior to the femoral vein as a conduit for regeneration of the sciatic nerve in the rat. The larger diameter of the jugular vein and its lack of valves provided less hindrance to regenerating axons(Wang, Costas et al. 1993b). ...
... Veins, which are abundantly available and have less donor site morbidity, have been found effective as nerve conduits for bridging short nerve gaps(Chiu, Janecka et al. 1982; Chiu, Lovelace et al. 1988; Suematsu, Atsuta et al. 1988; Risitano, Cavallaro et al. 1989; Wang, Costas et al. 1993a; Wang, Costas et al. 1993b; Benito-Ruiz, Navarro-Monzonis et al. 1994; Wang, Costas et al. 1995; Colonna, Anastasi et al. 1996; Ferrari, De Castro Rodrigues et al. 1999; Pu, Syed et al. 1999; Kelleher, Al-Abri et al. 2001; Rodrigues Ade and Silva 2001; Strauch, Rodriguez et al. 2001; Zhang, Blain et al. 2002). Nerve growth factors NGF have been used and found beneficial in enhancing the axonal regeneration within venous nerve conduits (Cordeiro, Seckel et al. 1989; Derby, Engleman et al. 1993) Other investigators tried to bridge the nerve gap with a three-dimensional materials that would work as a scaffold for the regenerating axons as muscle fibers (Norris, Glasby et al. 1988; Gattuso, Glasby et al. 1989; de Blaquiere, Curtis et al. 1994; Di Benedetto, Lassner et al. 1994; Whitworth, Dore et al. 1995; Roganovic, Savic et al. 1996; Fullarton, Glasby et al. 1998; Liu, Arai et al. 2001), collagen fiber bundles (Tong, Hirai et al. 1994), fibronectin-mats (Whitworth, Brown et al. 1995), polyamide sutures (Lundborg, Dahlin et al. 1997), and collagen matrix (Tranquillo, Girton et al. 1996). ...
... [9][10][11] Autogenous vein grafts are experimentally and clinically validated supportive tunnels for the regeneration and maturation of nerve fibers. [12,13] Depending on capacity to regenerate nerve endings, nerve sprouts with axonal migration provide skeletal structure that contains extracellular matrix components and can be used with various growth factor supplements when necessary. Thus, vein grafts have most of the required qualities for neural tube models. ...
... [22,23] Vein grafts are the most frequently used biological conduits, and autog-enous vein grafts have been widely used as biological conduits for the regeneration and maturation of nerve fibers in both experimental and clinical settings. [12,24,25] Vein grafts are nonimmunogenic, easier to obtain than nerve grafts, and last longer than bioabsorbable nerve tubes. Moreover, various alternatives are available to accommodate range of diameters, and autogenous tissue grafts do not need to be removed from the surgical field after nerve repair. ...
BACKGROUND: Presently described is research examining the ”stuffed nerve” technique to repair peripheral nerve defects.? METHODS: Twenty-one male Wistar Albino rats were divided into 3 groups of 7, and standard 10-mm defects were created in the sciatic nerve of all subjects. Rats were treated with autogenous nerve graft (Group 1), hollow vein graft (Group 2), or vein graft stuffed with shredded nerves (Group 3). After 12 weeks, electrophysiological and histomorphological analyses were performed to evaluate axonal regeneration. RESULTS: Rat groups were compared in terms of latency period and peak-to-peak potential. Latency period was significantly shorter and peak-to-peak potential was significantly greater in Group 1 than in Group 2. However, latency period and peak-to-peak potential did not differ significantly between Groups 1 and 3 or between Groups 2 and 3. To evaluate axonal regeneration, number of axons, axon diameter and myelin sheath thickness was compared between groups. Results indicated that axonal regeneration was similar in Groups 1 and 3, and was better than results seen in Group 2. CONCLUSION: The stuffed nerve technique is an alternative to autogenous nerve grafting and produces similar electrophysiological and histomorphological properties.
... Weiss (1944), working at the Department of Zoology at Chicago University, published his results with a segment of autologous artery bridging nerve defects in more than 700 animals, claiming its efficacy. The use of a vein as a nerve conduit was described in New York by Chiu (1982). Bora (1987) published his results using a polyester resorbable tube ( Figure 11). ...
This article reviews the history of peripheral nerve (PN) injuries and successive advances in their management by notable pioneers, an interesting topic that I chose for my Doctoral Thesis in 1990 in Madrid. Mentioning all their names and contributions is an obligatory tribute, and I offer my sincere apologies for inevitably leaving a few out. For half a century I have witnessed microsurgery advances, and also experienced frequent failures in my practice with the use of new techniques; a testimony that we are very far from achieving the ‘Holy Grail’ of complete PN recovery for these injuries. Our experience is often like a pendulum, from nihilism to optimism and vice versa. Many factors influence the results of PN repair. Fortunately, microsurgery has been a breakthrough but, too often, emergency surgery is carried out by surgeons without enough tools and experience, both very important factors in this field.
... A variety of conduits have been developed, including veins and synthetic grafts. Several studies (Chiu et al., 1982;Strauch et al., 1996) have used autogenous venous nerve conduits to successfully support axonal regeneration for short distances (less than a 3 cm gap). ...
Peripheral neuropathy is a common neurological issue that leads to sensory and motor disorders. Over time, the treatment for peripheral neuropathy has primarily focused on medications for specific symptoms and surgical techniques. Despite the different advantages of these treatments, functional recovery remains less than ideal. Schwann cells, as the primary glial cells in the peripheral nervous system, play crucial roles in physiological and pathological conditions by maintaining nerve structure and functions and secreting various signaling molecules and neurotrophic factors to support both axonal growth and myelination. In addition, stem cells, including mesenchymal stromal cells, skin precursor cells and neural stem cells, have the potential to differentiate into Schwann-like cells to perform similar functions as Schwann cells. Therefore, accumulating evidence indicates that Schwann cell transplantation plays a crucial role in the resolution of peripheral neuropathy. In this review, we summarize the literature regarding the use of Schwann cell/Schwann cell-like cell transplantation for different peripheral neuropathies and the potential role of promoting nerve repair and functional recovery. Finally, we discuss the limitations and challenges of Schwann cell/Schwann cell-like cell transplantation in future clinical applications. Together, these studies provide insights into the effect of Schwann cells/Schwann cell-like cells on cell therapy and uncover prospective therapeutic strategies for peripheral neuropathy.
... Current studies have focused on finding alternative methods for bridging nerve defects. Previous experiments have examined venous grafts as well as artificial and natural conduits (21,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Today's methods can support nerve regeneration; however, they have not consistently replicated the results obtained by autologous nerve transplantation (33). ...
Background: Peripheral nerve injuries remain a great challenge for microsurgery despite the significant progress in recent decades. The current gold standard is autogenous nerve grafting with a success rate as low as 50% in long gaps. Current studies have focused on finding alternative methods for bridging nerve defects. Previous data have demonstrated the role of human amniotic membrane in stimulating neural regeneration. On the other hand, adipose-derived mesenchymal stem cells can differentiate into all three germ layers and could support nerve repair. The purpose of this study was to compare the role of the human amniotic membrane with and without adipose tissue stem cells in sciatic nerve injury with gap in rats. Objectives: We aimed to evaluate the effectiveness of the human amniotic membrane with and without adipose-derived mesenchymal stem cells in sciatic nerve injury with gap in rats. Methods: Twenty-four male Wistar rats in four random groups were used in our study. In the first group, the nerve gap was repaired using the inverse resected nerve segment (Control group), the second group was repaired with a human amniotic membrane (AM group), the third group was repaired with an amnion sheet with seeded adipose-derived mesenchymal stem cells (AM/ADMSCs group), and the last group was not repaired, and both stumps were sutured to muscles. Results: All the animals underwent the procedures and survived without complication. The sciatic function index and hot plate test results were significantly improved in the AM and AM/ADMSCs groups compared to the Control group (as a gold standard of care) (P>0.05). Based on histopathology findings, regenerative nerve fibers were seen in the implanted area of both AM and AM/ADMSCs groups; however, nerve fibers were surrounded by significant fibrosis (scar formation) in the AM/ADMSCs group. The axon count in the Control group was significantly higher than both experimental groups (P < 0.01). Conclusions: Our study showed the role of amniotic membrane in the promotion of nerve regeneration in sciatic nerve injury with a gap, but adding adipose-derived mesenchymal stem cells not only has no extra benefits, but also causes more tissue scar.
... Non nerve grafts like muscles, veins have also shown potential in nerve repair after their decellularization such that it provides 3D support to the native cellsused [22][23][24]. (Chiu et al., 1982)The abovementioned limitations made it obligatory to search for better alternatives which brought into focus the tissue engineering approach. Tissue engineering which laid its foundation in 1980 ' s turned to be an impending force in the field of nerve tissue engineering. ...
Polysaccharides are high molecular weight biopolymers present in various flora and fauna in the ecological systems. Due to its high biocompatibility and versatile functions, these polymers are employed in various biomedical applications. Biocompatible polysaccharide coated metal nanoparticles are widely used for the theranostic management of cancer. Numerous literatures have reported the use of gold and iron oxide nanoparticles to be a potential agent for drug delivery and imaging. There are several commercially available biopolymer based metal nanoparticles, but none of these exhibits excellent biocompatibility and multifaceted functions. Based on these rationales, the current review attempted to focus on polysaccharide
coated gold and iron oxides nanoparticles and its impact on cancer management in past few decades
... 4,5 Vein and allograft conduits have also been implemented, particularly with sensory nerves, with varying success. [6][7][8][9][10][11][12] However, conduits may be less effective in larger gaps. [13][14][15][16] Processed nerve allografts (PNA) have emerged as an alternative to both autografts and conduits. ...
Background:
Processed nerve allograft (PNA) is an alternative to autograft for the reconstruction of peripheral nerves. We hypothesize that peripheral nerve repair with PNA in a military population will have a low rate of meaningful recovery (M ≥ 3) because of the frequency of blasting mechanisms and large zones of injury.
Methods:
A retrospective review of the military Registry of Avance Nerve Graft Evaluating Utilization and Outcomes for the Reconstruction of Peripheral Nerve Discontinuities database was conducted at the Walter Reed Peripheral Nerve Consortium. All adult active duty military patients who underwent any peripheral nerve repair with PNA for complete nerve injuries augmented with PNA visit were included. Motor strength and sensory function were reported as a consensus from the multidisciplinary Peripheral Nerve Consortium. Motor and sensory testing was conducted in accordance with the British Medical Research Council.
Results:
A total of 23 service members with 25 nerve injuries (3 sensory and 22 mixed motor/sensory) underwent reconstruction with PNA. The average age was 30 years and the majority were male (96%). The most common injury was to the sciatic nerve (28%) from a complex mechanism (gunshot, blast, compression, and avulsion). The average defect was 77 mm. Twenty-four percent of patients achieved a meaningful motor recovery. Longer follow-up was correlated with improved postoperative motor function (r = 0.49 and P = .03).
Conclusions:
The military population had complex injuries with large nerve gaps. Despite the low rate of meaningful recovery (27.3%), large gaps in motor and mixed motor/sensory nerves are difficult to treat, and further research is needed to determine if autograft would achieve superior results.
Type of study/level of evidence:
Therapeutic, Level III.
... Politis 20 described nervous chemotaxis, later confirmed by Lundborg 21 and Frey 22 , and opened the door to the research of new methods of nerve repair, namely, for the development of techniques based on conducting channels of the regenerating nerve. The use of a vein as a conduit for nerve regeneration between two stumps was tested by Chiu 23 in 1182, but with frequent collapses of the vein. In 1184, Keynes 24 tested ...
Intraoperative lesions of the recurrent laryngeal nerve (RLN) are rare, but have serious consequences. The authors present a new technique for repairing the RLN based on an experimental study using a vein-muscle graft between the tops of the RLN. The goal
is to restore normal movements of the vocal cord. Nine animals were operated on, six in the nerve reconstruction group (NRG) and three in the control group (CG). Eleven months later, the vocal cord movements were analysed, the voice was recovered and the histological analysis of the graft was carried out. The results showed that all the goats (100 %) of the NRG regained movement of the vocal cords. In addition, in five animals, the reinnervation occurred with movements symmetrical to those of the other vocal cord
and in another animal, they were almost symmetrical. The results for analysis of voice evolution of the NRG goats, obtained with objective and subjective tests, showed a good recovery of the “normal voice”. As for the histological study, only 50 % of the NRG cases demonstrated complete regeneration of the RLN. The results also showed that there was a selective / discriminative nervous tropism. Abductor and adductor fibres were attracted to similar ones on the other top, effectively reinnervating the laryngeal muscles. The method tested in this study, which was applied for the first time to repair RLN, is effective, inexpensive, simple and leaves no anatomical or functional sequelae. It is possible to extrapolate the results to humans.
... Blood vessels and striated muscles are the conduits which received the highest interest from study groups. A milestone for their use was the demonstration in the 1980s that vein grafts carrying injured nerves resulted in similar effects to autologous nerve grafting [17][18][19][20][21] . ...
The facial nerve is the most frequently damaged nerve in head and neck traumata. Repair of interrupted nerves is generally reinforced by fine microsurgical techniques; nevertheless, functional recovery is the exception rather than the rule. The so-called "post-paralytic syndrome", which includes synkinesia and altered blink reflexes, follows nerve injury. The aim of the present study was to investigate whether nerve-gap repair by an autologous vein, which had been filled with skeletal muscle, would improve axonal regeration, reduce neuromuscular junction polyinnervation and improve the recovery of whisking in rats with transected and sutured right buccal branches of the facial nerve. Vibrissal motor performance was examined with the use of a video motion analysis. Immunofluorescence was used to visualize and analyze target muscle reinnervation. The results taken together indicate a positive effect of muscle-vein combined conduit (MVCG) on recovery of whisking function after facial nerve reconstruction in rats. The findings support the recent suggestion that a venal graft with implantation of a trophic source, such as autologous denervated skeletal muscle, may promote the monoinnervation degree and improve the recovery of coordinated function of the corresponding muscles.
... Tissue-engineered nerve grafts (TENGs), which comprise nerve conduits in conjunction with supporting cells and growth factors, further facilitate nerve regeneration. The historical timeline of key events in the development of NGCs is shown in Scheme 1. [4][5][6][7][8][9][10][11][12][13][14][15][16] In this review, we first describe the anatomy of peripheral nerve and the pathology of PNI, and introduce the polymer-based NGCs and clinical NGCs, followed by the design principles for advanced NGCs based on physical and biochemical cues. Then, we focus on the latest advances in specific functional NGCs, including neuroprotection, antioxidation, vascular regeneration enhancement, and immune regulatory effects. ...
Bridging critical‐sized defects in peripheral nerves to achieve functional recovery is a challenge for orthopedic and hand surgeons. Inadequate regeneration of peripheral nerve axons often results in long‐term partial or total sensory and/or motor impairment. Currently, the best treatment available for long‐gap peripheral nerve regeneration is autologous nerve transplantation, while the successful implementation of this approach requires for secondary surgery and donor nerves. The nerve guide conduit (NGC) serves as an alternative to autograft of nerve, as it connects the proximal and distal ends of nerve defects and provides physical and biochemical guidances for axon regeneration. Functionalized NGCs enhance nerve regeneration by providing neuroprotection, antioxidation, vascular regeneration enhancement, and immune regulatory effects. In this review, the authors summarize the latest advances in functional polymer‐based NGCs for peripheral nerve regeneration and present the perspectives on the development of peripheral NGCs for potential clinical applications. Functional polymer‐based nerve guide conduits connect the proximal and distal ends of nerve defects and provide physical and biochemical guidance for axon regeneration, which enhances nerve regeneration by providing neuroprotection, antioxidation, angiogenesis, and immune regulation effects, indicating their great potential in clinical application.
... Naturally derived conduits, such as arteries, muscles and tendons, have been studied for bridging nerve defects, but vein tubes have received the most attention among researchers and even are used clinically. 84 88 Acellular tissue scaffolds are generated using techniques to retain a large portion of native ECM proteins while minimizing cellular debris and undesired immunological response (ie, rejection). Acellular tissues, despite their lack of cells and processing techniques, typically maintain a highly organized extracellular matrix structure providing an ideal scaffold structure for regeneration. ...
Despite advances in surgery, the reconstruction of segmental nerve injuries continues to pose challenges. In this review, current neurobiology regarding regeneration across a nerve defect is discussed in detail. Recent findings include the complex roles of non‐neuronal cells in nerve defect regeneration, such as the role of the innate immune system in angiogenesis and how Schwann cells migrate within the defect. Clinically, the repair of nerve defects is still best served by using nerve autografts with the exception of small, non‐critical sensory nerve defects, which can be repaired using autograft alternatives, such as processed or acellular nerve allografts. Given current clinical limits for when alternatives can be utilized, advanced solutions to repair nerve defects demonstrated in animals are highlighted. These highlights include alternatives designed with novel topology and materials, delivery of drugs specifically known to accelerate axon growth, and greater attention to the role of the immune system. This article is protected by copyright. All rights reserved.
... Additionally, the support must have characteristics such as biocompatibility, biodegradability, porosity (for interaction with extracellular matrix receptors, which allows attachment of anchoring ligands, and neuronal growth factors, which favors cell proliferation), and adequate biological and mechanical properties so that the axons can grow, thus generating the necessary environment for an adequate regeneration [3,4]. Substances or cells that positively influence axonal regeneration have been used as supports, including adipose tissue mesenchymal stem cells, which have a paracrine response to the secretion of nerve growth factors [5][6][7][8][9][10][11][12], in addition to the ability to differentiate into Schwann cells (SC), which are crucial for axonal growth [13][14][15]. Several studies have shown that fibrin directs axonal growth during regeneration and can be obtained from platelet-rich plasma (PRP). ...
... Autogenous vein grafts to bridge small gaps helps control axonal regrowth but is limited to 2 to 3 cm in humans. 8,9,39,49 Herbert and Filan published a series of 14 patients in whom nerve stumps were implanted into adjacent veins, which were then ligated distally. 22 At final follow-up, ranging 2 to 33 months, 9 were symptom free and 3 had minor residual symptoms (86% success). ...
... Nerve and vascular grafts, denatured muscle fibers, and fascial layers are examples of natural tubulization. [23][24][25][26] Polyglycolic acid, polyglycan, polyethylene, and silicone were used for synthetic tubulization. [23,27,28] Yapici et al. [22] reported that vascularized nerve conduit graft showed better regeneration compared to non-vascularized nerve conduit graft but that it cannot be an alternative to autogenous nerve graft. ...
BACKGROUND: The aim of our study is to minimize the morbidity related to nerve injury by determining the protective effects of gabapentin in experimental sciatic nerve injury and end-to-end anastomosis model in rats and to guide clinical studies on this subject. METHODS: In our study, 40 adult male Sprague-Dawley rats were randomly divided into the following five groups: I: Only surgical intervention was applied; II: The sciatic nerve was cut properly and was repaired by end-to-end anastomosis. No additional procedure was performed; III: A single dose of gabapentin at 30 mg/kg was given after anastomosis; IV: 30 mg/kg gabapentin was given for 3 days after anastomosis; and V: 30 mg/kg gabapentin was given for 7 days after anastomosis. The experiment was terminated with high-dose thiopental (50 mg/kg) 60 days after the surgical intervention. The right sciatic nerve was taken from all animals. The obtained sections were examined immunohistopathologically. RESULTS: Immunohistochemical properties and Schwann cell proliferation were found to be statistically significantly lower in the control group than in the other groups. Schwann cell proliferation was higher in Group 3 than in Group 5. Immunohistochemical changes were significantly lower in Group 4 than in Group 3. Axonal degeneration was also higher in Group 4 than in Group 3. CONCLUSION: Gabapentin promotes neurological recovery histopathologically in peripheral nerve injury due to its neuroprotective properties. Our study results show that gabapentin can be used as an adjunctive therapy to primary surgical treatment after peripheral nerve injury.
... Autogenous vein grafts to bridge small gaps helps control axonal regrowth but is limited to 2 to 3 cm in humans. 8,9,39,49 Herbert and Filan published a series of 14 patients in whom nerve stumps were implanted into adjacent veins, which were then ligated distally. 22 At final follow-up, ranging 2 to 33 months, 9 were symptom free and 3 had minor residual symptoms (86% success). ...
... Literature suggest that the ideal nerve conduit, for successful nerve regeneration, should be biocompatible with the surrounding nerve tissues, causing minimal tissue inflammatory reaction; they should stimulate axonal regeneration through its entire length and they should biodegrade as the nerve regenerates. In addition to its biochemical role, each nerve conduit would also benefit from certain mechanical features: that it should be easily manufactured, readily available, semiflexible, and easily manipulated in the surgical setting [4,16,17,[20][21][22][23]. But also if the conduit responses to all these features, like muscle vein combined conduit [24,25], the main limitation of nerve regeneration inside conduits remains the distance between the stumps that may be bridged. ...
The amnion muscle combined graft (AMCG) conduits showed good clinical results in peripheral nerves gap repair. It combines the human amniotic membrane with autologous skeletal muscle fibres. These results seem attributable to the biological characteristics of human amniotic membrane: Pluripotency, anti-inflammatory and low immunogenicity.We here evaluate the final outcome of nerve regeneration morphologically and functionally, across the AMCG compared to nerve autograft. Fourteen Wistar rats were divided into two groups: In Group A, including 6 rats, the left forelimb was treated performing a 1.5 cm length gap on median nerve that was then reconstructed with a reverse autograft. In Group B, including 8 rats, the gap was reconstructed with AMCG. Functional results were evaluated at 30, 60 and 90 days performing grasping tests. Morphological and stereological analyses were performed at T90 using high-resolution light microscopy and design-based stereology. The AMCG conduits revealed nerve fibres regeneration and functional recovery. Functional recovery was observed in both groups with AMCG conduits group showing lower values and a regeneration of median nerves with more myelinated fibres with the same axon size, but thinner myelin than the autograft group. Though the autograft remains the gold standard to restore wide nerve gaps, the AMCG conduit has proved to be effective in enabling nerve regeneration through a critical rat’s nerve gap of 15 mm. These findings empirically support the great clinical results obtained using AMCG conduit to restore traumatic nerve’s gap from 3 to 6 cm of mixed forearm nerves. Open image in new window
... N erve coaptation is important for successful nerve reconstruction. Different techniques for enhancement of nerve regeneration after microsurgical nerve repair have been described previously (1)(2)(3)(4)(5)(6)(7)(8)(9). Significant loss of nerve tissue necessitates the use of a nerve graft, while nerve regeneration through a large peripheral nerve gap will not be successful unless a conduit is used. ...
In microsurgical nerve repair, the epineural sleeve technique can be used to bridge short nerve defects and to cover the coaptation site with the epineurium of the nerve stump. The epineurium serves as a mechanical aid to reduce gap size, and increase repair strength, effectively assisting nerve regeneration. This article presents a 32-year-old patient who experienced complete transection of the median nerve at the distal forearm, which was treated with the epineural sleeve graft reconstruction technique. Nerve regeneration was followed-up for 18 months and evaluated with the Rosén and Lundborg scoring system. The final outcome was excellent; at the last follow-up, the patient experienced complete sensory and motor function of the median nerve.
... Medicine of the thumb, opponents and 1st and 2nd lumbricals which can result in claw fingers. When tension-free suturing is possible, a simple repair is the preferred procedure; however, patients with loss of nerve tissue, resulting in a nerve gap, are considered for nerve grafting procedure 20 . In present study patients with acute low median nerve injury were selected. ...
Currently there is a low success rate of function restoration with aid of surgical techniques. Therefore
Peripheral nerve repair and healing have gained an increased attention in recent decades; many studies have
investigated this subject. There is a clear need for biomedical engineering research to develop novel
strategies to improve outcomes following nerve damage. Double-blinded randomized control trial was
designed with 10 patients with acute median nerve injuries at wrist who underwent epiperineurorrhaphy
with microsurgical technique. 5 cases received outologus platelet rich plasma (PRP) at repair site. Patients
were followed up for evaluation of recovery for 1 year. The average recovery percentage of all variants in
case group was 70.33% and 67.38% in control group. The average speed of recovery of all variants in case
group was 8.16% and 10.21% in control group in aforementioned time interval. Remarkable recovery was
found in pinch power, amplitude and distal latency-motor in both group. Majority of variants had better
results after PRP injection at repair site but these changes was not remarkable.
... These materials can provide support for the nerve in the short term and degrade to innocuous products after complete nerve regeneration. Some authors have used autogenetic epineurium, 34,35 autogenic veins and autogenic small arteries, and even muscle fibers [36][37][38][39][40] to repair peripheral nerve injury and reported satisfying results. ...
Qiang Ao Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, Liaoning, Peoples’ Republic of China Abstract: Clinical repair of a nerve defect is one of the most challenging surgical problems. Autologous nerve grafting remains the gold standard treatment in addressing peripheral nerve injuries that cannot be bridged by direct epineural suturing. However, the autologous nerve graft is not readily available, and the process of harvesting autologous nerve graft results in several complications. Thus, it is necessary to explore an alternative to autologous nerve graft. In the last few decades, with significant advances in the life sciences and biotechnology, a lot of artificial nerve grafts have been developed to aim at the treatment of peripheral nerve disruptions. Artificial nerve grafts range from biological tubes to synthetic tubes and from nondegradable tubes to degradable tubes. Among them, acellular nerve allografts and artificial nerve repair conduits are two kinds of the most promising substitutes for nerve autografts. The history, research status, and prospect of acellular nerve allografts and artificial nerve repair conduits are described briefly in this review. Keywords: peripheral nerve injury, repair, acellular nerve graft, nerve conduit
... Biological conduits for nerve repair include epimysium conduit fi lled with skeletal muscle fi bers (Yang et al. 2013 ), vein (Chiu et al. 1982 ), artery (Gulati 1989 ), skeletal muscle (Jiming et al. 1986 ), epineurial sheath (Karacaoğlu et al. 2001 ) or muscle-vein combined conduit (Geuna et al. 2004 ). Inside-out vein and artery grafts provide the growing axons to be in contact with the adventitia, which is rich in collagen, and the normal orientation of the grafts provides the growing axons to be in contact with the endothelial basal membrane which is rich in laminin, a component of Schwann cell basal membrane. ...
There is a general belief that regeneration in the Peripheral Nervous System (PNS) is a successful event, however complete functional regeneration is seldom achieved in patients that have suffered a nerve traumatic injury. In fact, what is clinically observed is that these patients live with permanent disabilities that interfere negatively in their daily routine activities. In injuries where there is tissue loss a direct neurorraphy is not possible without causing nerve tension and, therefore, another repair technique is needed. Clinically, these lesions are repaired by nerve autograft, a technique that requires a second surgery to harvest a segment of a donor nerve, a disadvantage of the method. Also, the area covered by the donor nerve becomes denervated and its function is lost. Other techniques that are used by surgeons when the proximal stump is not available are end-to-side coaptation and nerve transfer. Experimental studies aiming at developing alternative strategies that can improve nerve regeneration have increased over the last decades. Particularly, the search for nerve guiding conduits that can be used to bridge the nerve defect has received much attention by researchers all over the world. These conduits can be made by either synthetic or biological materials, but ideally, they should be biodegradable and biocompatible, have adequate permeability so as to allow the entrance of nutrients into the tube lumen and yet avoid the passage of cells that can interfere negatively in the regeneration processes, such as fibroblasts and inflammatory cells. Other therapeutic strategies such as gene, cell and molecular therapies as well as physical therapies (exercise, electrical and LASER therapy) have also been tested in experimental studies with positive results. In this chapter we review the literature covering all these strategies in terms of experimental studies and existing clinical trials.
... 1,29 Different procedures to bridge a nerve gap have been in-vestigated, such as the use of heterologous nerve grafts or different autologous tissues. 5,[9][10][11]28,40,49 Moreover, a number of synthetic resorbable and nonresorbable materials have been proposed to enhance and support nerve regeneration across nerve gaps. In the past, inert materials were used to develop synthetic nerve guides but caused complications such as compression syndromes, scar formation, or toxic tissue reactions, which restricted their application as useful materials. ...
Treatment of peripheral nerve injury is not always satisfactory. To improve results, specific adjuvant methods have been used, such as platelet-rich fibrin (PRF) and vein conduits. The goal of this study was to assess whether use of PRF and vein conduits after nerve suture improves nerve regeneration as measured by a functional score and histomorphometry analysis. Ten isogenic spontaneously hypertensive rats were randomly assigned to 4 experimental procedures: 1) Sham group (n = 10); 2) Nerve graft (NG) group (n = 10); 3) Nerve graft covered with a vein conduit (NGVC) (n = 10); and 4) Nerve graft covered with a vein conduit pre-filled with PRF (NGVCP) (n = 10). Nerve repair results were evaluated on: sciatic functional index (SFI) at 0, 30, 60 and 90 days; morphometric and morphologic analysis of the distal nerve; and histological analysis of Fluoro-Gold® stained motor neurons in the anterior horn of the spinal cord. Compared to the Sham control group, the NGVC and NGVCP groups exhibited lower SFI on all measures. The NGVC group showed improvement in SFI at day 90, which was significant compared to the NG group. Fiber and axon diameters were comparable in the NGVC and NGVCP groups, which were both significantly lower than in the Sham and NG groups. Significant improvement was expected with PRF, but in fact the release of factors from this substance was not as effective as hoped.
The treatment of peripheral nerve defects has always been one of the most challenging clinical practices in neurosurgery. Currently, nerve autograft is the preferred treatment modality for peripheral nerve defects, while the therapy is constantly plagued by the limited donor, loss of donor function, formation of neuroma, nerve distortion or dislocation, and nerve diameter mismatch. To address these clinical issues, the emerged nerve guide conduits (NGCs) are expected to offer effective platforms to repair peripheral nerve defects, especially those with large or complex topological structures. Up to now, numerous technologies are developed for preparing diverse NGCs, such as solvent casting, gas foaming, phase separation, freeze‐drying, melt molding, electrospinning, and three‐dimensional (3D) printing. 3D printing shows great potential and advantages because it can quickly and accurately manufacture the required NGCs from various natural and synthetic materials. This review introduces the application of personalized 3D printed NGCs for the precision repair of peripheral nerve defects and predicts their future directions. The personalized nerve guide conduits are quickly and accurately manufactured from various natural and synthetic materials by a three‐dimensional printing technique, which meets personalized imaging data to repair nerve defects of complex anatomical structures with the assistance of different growth factors and cells.
The nervous system is the most important system of the body and damaging this system could be lethal for humans. Restoring the function of a damaged nervous system has always been a challenge due to the complexity of this system and its limited ability of regeneration. Furthermore, several obstacles exist in the repair process of the nervous system. In the central nervous system (CNS) limited clearance of myelin and formation of inhibitory glial scars make regeneration difficult. There is no effective clinical treatment for damages in the CNS while current treatments focus on stabilization and prevention of further damage and consequently on rehabilitation and preparation of prosthetics and mechanical aids. In peripheral nervous system (PNS) damages, the management may be a nerve autograft or allograft while shortage of donors for nerves makes the situation difficult. Size inequality between the donor nerve and the recipient, danger of neuroma formation, and occurrence of infectious diseases are other problems associated with PNS, while indeed complete recovery of function is still not common. Several studies have illustrated that implying tissue engineering strategies for neural repair may lead to considerable improvements in damaged nervous tissues.
The gold-standard method for reconstruction of segmental nerve defects, the autologous nerve graft, has several drawbacks in terms of tissue availability and donor site morbidity. Therefore, feasible alternatives to autologous nerve grafts are sought. Muscle-in-vein conduits have been proposed as an alternative to autologous nerve grafts almost three decades ago, given the abundance of both tissues throughout the body. Based on the anti-inflammatory effects of veins and the proregenerative environment established by muscle tissue, this approach has been studied in various preclinical and some clinical trials. There is still no comprehensive systematic summary to conclude efficacy and feasibility of muscle-in-vein conduits for reconstruction of segmental nerve defects. Given this lack of a conclusive summary, we performed a meta-analysis to evaluate the potential of muscle-in-vein conduits. This work’s main findings are profound discrepancies regarding the results following nerve repair by means of muscle-in-vein conduits in a preclinical or clinical setting. We identified differences in study methodology, inter-species neurobiology and the limited number of clinical studies to be the main reasons for the still inconclusive results. In conclusion, we advise for large animal studies to elucidate the feasibility of muscle-in-vein conduits for repair of segmental defects of critical size in mixed nerves.
The gold-standard method for reconstruction of segmental nerve defects, the autologous nerve graft, has several drawbacks in terms of tissue availability and donor site morbidity. Therefore, feasible alternatives to autologous nerve grafts are sought. Muscle-in-vein conduits have been proposed as an alternative to autologous nerve grafts almost three decades ago, given the abundance of both tissues throughout the body. Based on the anti-inflammatory effects of veins and the proregenerative environment established by muscle tissue, this approach has been studied in various preclinical and some clinical trials. There is still no comprehensive systematic summary to conclude efficacy and feasibility of muscle-in-vein conduits for reconstruction of segmental nerve defects. Given this lack of a conclusive summary, we performed a meta-analysis to evaluate the potential of muscle-in-vein conduits. This work’s main findings are profound discrepancies regarding the results following nerve repair by means of muscle-in-vein conduits in a preclinical or clinical setting. We identified differences in study methodology, inter-species neurobiology and the limited number of clinical studies to be the main reasons for the still inconclusive results. In conclusion, we advise for large animal studies to elucidate the feasibility of muscle-in-vein conduits for repair of segmental defects of critical size in mixed nerves.
Peripheral nerve surgery encompasses the repair of primary nerve transection, the reconstruction of nerve gaps as well as the management of painful nerve conditions including end neuroma and neuroma-in-continuity. The gold standard for nerve repair is considered to be microsurgical suture with attention to restoring alignment and providing close approximation of the nerve ends without distortion of the fascicle architecture.
Peripheral nerve injuries are known to have devastating impact on a patient’s quality of life. These injuries can occur after high-impact activities, traumatic injuries, or motor vehicle accidents. When a nerve is transected or crushed, it encounters roadblocks that must be overcome for efficient and effective neural regeneration. Although microsurgical reconstruction offers hope for improved results after surgery, surgical manipulations alone have not optimized the outcomes. Tensionless, primary repair is the gold standard for nerve injuries without gaps, whereas injuries with segmental defects challenge standard surgical techniques for nerve repair. As such, modalities such as structural guides and luminal additives are and continue to be developed in an attempt to improve outcomes. Furthermore, research has focused on accelerating the process of regeneration after injury through pharmacological agents, implantation of stem cells, and gene therapy, all for the ultimate purpose of better functional recovery at the end. In this chapter we review the current literature relevant to the utilization of available biologic augments in peripheral nerve repair.
Over the recent years, several methods have been experienced to repair injured peripheral nerves. Among investigated strategies, the use of natural or synthetic conduits was validated for clinical application. In this study, we assessed the therapeutic potential of vein guides, transplanted immediately or two weeks after a peroneal nerve injury and filled with olfactory ecto-mesenchymal stem cells (OEMSC). Rats were randomly allocated to five groups. A3 mm peroneal nerve loss was bridged, acutely or chronically, with a 1 cm long femoral vein and with/without OEMSCs. These four groups were compared to unoperated rats (Control group). OEMSCs were purified from male olfactory mucosae and grafted into female hosts. Three months after surgery, nerve repair was analyzed by measuring locomotor function, mechanical muscle properties, muscle mass, axon number, and myelination. We observed that stem cells significantly (i) increased locomotor recovery, (ii) partially maintained the contractile phenotype of the target muscle, and (iii) augmented the number of growing axons. OEMSCs remained in the nerve and did not migrate in other organs. These results open the way for a phase I/IIa clinical trial based on the autologous engraftment of OEMSCs in patients with a nerve injury, especially those with neglected wounds.
Background:
Treating ring avulsion injuries continues to challenge the reconstructive hand surgeon. The complex operation draws from plastic surgery and orthopedic surgery principles to provide soft-tissue coverage, skeletal fixation, tendon repair, and neurovascular reconstruction. Furthermore, the application of microsurgical techniques has enabled the revascularization and replantation of completely avulsed fingers.
Methods:
A retrospective review of 22 consecutive ring avulsion injuries (seven amputations, five replantations, and 10 revascularizations) from 1987 to 2015 performed by a single senior surgeon (D.T.W.C.) was conducted.
Results:
Of these 22 ring avulsions, 10 revascularizations, five replantations, and seven amputations (five because of clinical factors, and two because of patient request) were performed. None of the 15 replantations and revascularizations resulted in loss of the ring finger or necrosis of the revascularized tip.
Conclusions:
With proper patient selection, appropriate level of injury identification, and meticulous surgical execution, the restoration of form and function to the hand is feasible in ring avulsion injuries.
Clinical question/level of evidence:
Therapeutic, IV.
Facial nerve paralysis profoundly impairs an individual’s quality of life, physical health, and self-image. Dynamic surgical correction of facial paralysis seeks to restore symmetry and tone, thereby achieving voluntary movement and expression. The selection of technique is dictated by anatomy and timing of the injury. Reinnervation techniques, including primary surgical repair, nerve grafts, tissue-engineered constructs, and nerve transfers, are feasible within 1–2 years, while neuromuscular junctions are viable. More chronic injuries require reanimation techniques such as free muscle transfers and regional muscle transfers or static approaches. Emerging research and technology include advances in nerve regeneration as well as bioelectrical interfaces. These innovative approaches hold promise for enhancing the existing therapeutic arsenal for rehabilitating injury and restoring facial nerve function after facial palsy.
nerve repair after being transplanted in peripheral nerve injury. The aim of this study was to determine the beneficial effect of allograft Schwann cells on electrophysiological outcome after transection of the sciatic nerve in rats.
Methods: Twenty adult male Wistar rats (200-250 g) were used in this study and left sciatic nerve was cut 10 mm in all of them and randomly divided into two groups. Then, the experimental (n=10) and control (n=10) groups received silicon tube with Schwann cells and silicon tube without Schwann cells respectively. Electrophysiological studies were performed 8 weeks after transplantation.
Results: Electrophysiological study in experimental animals showed that amplitude of nerve action potential is higher and latency is less as compared to the control group (p<0.05).
Discussion: The combination of different strategies such as silicon tube and Schwann transplantation has a more effective role in nerve repair.
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Abstract
We study the influence of blood flow on the neuroma formation after transposition of the nerve stump into a vein. A total of 30 rats were divided into two groups. In group (I), a 10-mm segment of the femoral vein was excluded from the blood stream. A venotomy was performed in the middle of this segment. The proximal nerve stump of femoral nerve was transposed into the lumen of the femoral vein via a venotomy and held with an epineural suture through the venous wall. In group (II), the same technique was used as in group (I) but without exclusion of the vein segment from blood flow. The control side of the femoral nerve was transected and then was left in place. All animals were sacrificed after 28 weeks. Histopathological evaluation was performed postoperatively; serial transverse sections were made to find the largest diameter of the neuroma. Selected specimens were processed for electron microscopy examination. The following parameters were assessed in both the groups: Cross-sectional area of neuromas; myelinated axons; and neural tissue to connective tissue ratio. In group (I), the proximal end of the tibial nerve formed a nonclassic neuroma. In group (II), the proximal end of the tibial nerve formed a nonclassic neuroma smaller in diameter than group (I). The proximal end of the femoral nerve of the control sides in both groups formed a classic neuroma larger in diameter than the experimental sides in both the groups. A Kruskal–Wallis H test showed that there was a statistically significant difference in myelinated axons between the different groups, X² (3) = 36.19, p < 0.001. The average neural tissue to connective tissue ratio in the control group (I) ranged from 39.2 to 85.8%, but on the experimental side, it was more or less equalized. The average of a neural tissue to connective tissue ratio of the group (II) ranged from 59.1 to 63.9% in the treatment sides as compared to 28.6 to 82.4% in the control sides. The clinical experience utilizing the same technique in the treatment of 10 patients of painful neuromas of the superficial radial nerve and digital nerves were presented with encouraging results. The blood flow has a considerable effect on neuroma formation. We recommend a further study to know the fine details about the exact role of blood as the bloodstream may carry away neurotrophic factors that may also be released by the nerve stump itself.
Keywords
Influence of blood flow on the neuroma formation - Transposition of the nerve stump into vein on neuroma - management of neuroma
Processed nerve allografts (PNAs) have been demonstrated to have improved clinical results compared with hollow conduits for reconstruction of digital nerve gaps less than 25 mm; however, the use of PNAs for longer gaps warrants further clinical investigation. Long nerve gaps have been traditionally hard to study because of low incidence. The advent of the RANGER registry, a large, institutional review board-approved, active database for PNA (Avance Nerve Graft; AxoGen, Inc, Alachua, FL) has allowed evaluation of lower incidence subsets. The RANGER database was queried for digital nerve repairs of 25 mm or greater. Demographics, injury, treatment, and functional outcomes were recorded on standardized forms. Patients younger than 18 and those lacking quantitative follow-up data were excluded. Recovery was graded according to the Medical Research Council Classification for sensory function, with meaningful recovery defined as S3 or greater level. Fifty digital nerve injuries in 28 subjects were included. There were 22 male and 6 female subjects, and the mean age was 45. Three patients gave a previous history of diabetes, and there were 6 active smokers. The most commonly reported mechanisms of injury were saw injuries (n = 13), crushing injuries (n = 9), resection of neuroma (n = 9), amputation/avulsions (n = 8), sharp lacerations (n = 7), and blast/gunshots (n = 4). The average gap length was 35 ± 8 mm (range, 25-50 mm). Recovery to the S3 or greater level was reported in 86% of repairs. Static 2-point discrimination (s2PD) and Semmes-Weinstein monofilament (SWF) were the most common completed assessments. Mean s2PD in 24 repairs reporting 2PD data was 9 ± 4 mm. For the 38 repairs with SWF data, protective sensation was reported in 33 repairs, deep pressure in 2, and no recovery in 3. These data compared favorably with historical data for nerve autograft repairs, with reported levels of meaningful recovery of 60% to 88%. There were no reported adverse effects. Processed nerve allograft can be used to reconstruct long gap nerve defects in the hand with consistently high rates of meaningful recovery. Results for PNA repairs of digital nerve injuries with gaps longer than 25 mm compare favorably with historical reports for nerve autograft repair but without donor site morbidity.
Im Folgenden gehen wir auf die grundlegenden Techniken mikrochirurgischer Nervenoperationen ein. Spezifische Beschreibungen von Operationsabläufen bei traumatischen Läsionen, Tumoren und Kompression finden sich in den entsprechenden Kapiteln. ▶ Kap. 4 „Traumatische Nervenläsionen“ enthält zudem Kasuistiken, die jede der hier beschriebenen Techniken detailliert am Fallbeispiel erläutert und abbildet.
Nerve regeneration was examined in 108 mouse sciatic nerves in a prospective morphometric study in which a new anastomotic technique using nitrocellulose paper was compared with conventional suturing and simple sectioning.
Mice were randomly allocated to one of the three arms of the trial and sciatic nerves were examined following surgery at time intervals up to 8 weeks. Serial sections were taken for qualitative and quantitative morphometric analyses. Counts demonstrated that the rate of regeneration was faster in the nitrocellulose group than following nerve section alone, but that the suture group was even better. However, 8 weeks after surgery, there were no significant differences in myelinated axon counts 4 mm distal to the site of section between any of the experimental groups. The superlative regenerative capacity of rodent axons may limit the applicability of this model to human nerve tissue.
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.
Depuis son introduction dans les années 1880, la restauration de la fonction nerveuse après une lésion traumatique nerveuse périphérique a bénéficié de multiples progrès (1) : le développement du microscope optique, l’amélioration des techniques microchirurgicales, une meilleure compréhension l’anatomie nerveuse intraneuronale. De même, les études cliniques et fondamentales ont permis de mieux comprendre la physiopathologie de la régénération nerveuse et donc les différentes étapes de réparation. Il y a plusieurs facteurs qui influencent la qualité de la récupération nerveuse périphérique après un traumatisme nerveux : le délai entre le traumatisme et la chirurgie, l’âge du patient, le mécanisme (section nette ou écrasement), le niveau de la lésion (proximal ou distal) et les lésions associées (tissus mous, artères) (2–4). Tous ces facteurs doivent être pris en compte pour choisir la technique de réparation nerveuse la mieux adaptée à chaque patient et ainsi optimiser la qualité de la réparation nerveuse.
Surgical treatment represents only a part, albeit a significant one, of nerve repair and recovery. In addition, several forms of physical and medical treatment can improve results in diminishing scar formation, encouraging regeneration, maintaining muscle trophism or joint mobility during denervation, and re-educating the sensory and motor functions. Among those that we routinely use are the following:
— Steroids: against scar-formation
— X-ray therapy: against scar formation
— Magnetic therapy: to reduce fibrosis and improve elastic tissue
— Orthosis: to avoid deformities, subluxation, and muscle exhaustion
— Electrotherapy: to maintain muscle trophism (used on nerves and on muscles)
— Physiotherapy: to maintain muscle trophism and joint mobility
— Gangliosides: to improve nerve regeneration
— Re-education: motor and sensory
Following the section of a nerve, suture is either immediate or secondary and sometimes makes use of nerve grafts. It is the problem of establishing a bridge between two nerve ends which has particularly attracted our attention. Our experimental study involved the section of 8 mm of common fibular nerve, with the interposition of a 10-mm venous graft replacing the missing portion of nerve. Electrophysiological, histological, and immunological evaluations were carried out over a period ranging from 4 to 12 weeks of nerve regeneration.
In this study, we investigated the feasibility of using autologous vein graft and platelet-derived growth factors to bridge transected cavernous nerve in a rat model. A short defect in the bilateral cavernous nerve was created and repaired with vein graft from the right jugular vein or vein graft plus platelet-derived growth factors. The 32 rats were divided into four groups, namely Group 1 - no repair as a negative control, Group 2 - vein graft alone, Group 3 - vein graft plus platelet-derived growth factors, and Group 4 - sham operation as a positive control. We evaluated nerve regeneration and functional recovery using retrograde tracing study with FluoroGold, Toluidine blue staining of cavernous nerve, and the intracavernous pressure at 3 months. Three months after surgery, rich FluoroGold-positive cells were observed in the sham and vein graft plus platelet-derived growth factors group, but very few were found in the no repair group. The number of myelinated axons of regenerated cavernous nerve and intracavernous pressure were increased obviously in the two vein graft groups, especially in the vein graft plus platelet-derived growth factors group. These findings confirm the feasibility of using autologous vein as guides for cavernous nerve regeneration, and the regeneration can be further enhanced when the vein is filled with platelet-derived growth factors.
Despite recent efforts, there is still no clinically attractive alternative to nerve or vein autografts for repair of peripheral nerve defects. Much research is being devoted to the creation of the optimum nerve guidance channel, which will most likely incorporate multiple forms of stimuli for the regenerating nerve. The synthesis of additional novel and interactive biomaterials will open many doors for tissue engineering efforts in the nervous system. Biotechnology will also play a larger role, either by incorporation of cells genetically engineered to secrete neurotrophic or survival factors, or by direct incorporation of specifically tailored recombinant peptides or proteins (for example, adhesive ligand sequences, growth factors, enzyme pockets, and catalytic or inhibitory antibody fragments). In addition, drug delivery technology will become more critical for the design of the ideal nerve guidance channel (NGC). Techniques by which a series of bioactive molecules could be released over time in sequence with stages of regeneration may ultimately enhance repair in the PNS (peripheral nervous system), and potentially even in the CNS (central nervous system). In addition, more quantitative and uniform methods of analyzing regeneration need to be realized. Quantitative molecular analyses must be conducted in parallel with more phenomenological studies, so that ultimately, mechanistic models can be developed to make a priori predictions based on the biological responses of the regenerating nerve to stimulatory and inhibitory cues.
Sometimes serious tension occurs in the radial nerve when doing internal fixation for distal humerus shaft fracture or neurorrhaphy for radial nerve injury. Medial transposition of radial nerve on fracture site can avoid direct radial nerve injury by fracture fragment, radial nerve tension by plating for distal humerus shaft fracture, and also safe from neural tension during neurorrhaphy of damaged radial nerve. We reported here total 6 cases of backward transposition of radial nerve including 2 cases of radial nerve injury associated with humerus fracture and 4 cases of comminuted fracture of humerus shaft.
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