Use of nerve conduits in peripheral nerve repair

Studies on nerve conduits for peripheral nerve regeneration have concentrated on the manipulation of various conduit materials to avoid sacrificing native nerve in the clinical situation. With the proliferation of available nerve growth-stimulating factors, the focus is shifting experimentally toward molecular biologic manipulation, with the addition of these materials as substrates within the conduit. The clinical use of conduits has concentrated on the use of autogenous tissue, with a few examples of polyglactin (PGA) mesh and silicone. Ultimately, as yet, conduit material does not seem to have a profound effect on outcome. Substrate manipulation has not yet had clinical application. An important problem that remains, both experimentally and clinically, is overriding the size of the maximal gap that can be bridged successfully, as well as obtaining good functional sensory and motor recovery, compared with the use of nerve grafts. Advances in molecular biology may reveal further details about the nerve growth phenomenon, the precise sequencing of the substrate materials that are effective in promoting nerve growth, and when they should be applied. Advances in chemical engineering may provide additional biologically stable materials that have the ability to integrate growth-enhancing agents or factors into the lumen of the conduit.     

Luminal fillers in nerve conduits for peripheral nerve repair

The use of nerve conduits as an alternative for nerve grafting has a long experimental and clinical history. Luminal fillers, factors introduced into these nerve conduits, were later developed to enhance the nerve regeneration through conduits. Though many luminal fillers have been reported to improve nerve regeneration, their use has not been subjected to systematic review. This review categorizes the types of fillers used, the conduits associated with fillers, and the reported performance of luminal fillers in conduits to present a preference list for the most effective fillers to use over specific distances of nerve defect.     

Use of motor nerve material in peripheral nerve repair with conduits

We have recently shown in experimental nerve injury models that nerve regeneration is enhanced across a motor nerve graft as compared with a sensory nerve graft. To test the hypothesis that nerve architecture may mediate the beneficial effect of motor nerve grafting, we developed a model of disrupted nerve architecture in which motor and sensory nerve fragments were introduced into silicone conduits. Lewis rats were randomized to 5 experimental groups: nerve repair with motor nerve fragments, sensory nerve fragments, mixed nerve fragments, saline-filled conduit (negative control), or nerve isograft (positive control). At 6, 9, or 12 weeks, animals were sacrificed and nerve tissues were analyzed by quantitative histomorphometry. No significant differences were observed between the motor, sensory, and mixed nerve fragment groups. These findings suggest that intact nerve architecture, regardless of neurotrophic or biochemical factors, is a prerequisite for the beneficial effect of motor nerve grafting.     

Overcoming short gaps in peripheral nerve repair: conduits and human acellular nerve allograft

Nerve conduits and acellular nerve allograft offer efficient and convenient tools for overcoming unexpected gaps during nerve repair. Both techniques offer guidance for migrating Schwann cells and axonal regeneration though utilizing very different scaffolds. The substantially greater amount of animal and clinical data published on nerve conduits is marked by wide discrepancies in results that may be partly explained by a still poorly defined critical repair gap and diameter size. The available information on acellular allografts appears more consistently positive though this tool is also hampered by a longer but also limited critical length. This article reviews the current relative literature and examines pertinent parameters for application of both acellular allograft and nerve conduits in overcoming short nerve gaps.     

Spatially controlled delivery of neurotrophic factors in silk fibroin-based nerve conduits for peripheral nerve repair

Restoration with sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Silk has shown clinical promise for numerous tissue engineering applications due to its biocompatibility, impressive mechanical properties, and Food and Drug Administration approval. The aim of this study was to evaluate the efficacy of silk fibroin--based nerve guides containing glial cell line-derived neurotrophic factor (GDNF) in a long-gap sized (15 mm) rat sciatic nerve defect model. Four groups of nerve conduits were prepared: (1) silk conduits with empty silk microspheres, (2) silk conduits with GDNF-loaded silk microspheres uniformly distributed in the conduit wall, (3) silk conduits with GDNF-loaded silk microspheres in a controlled manner with the highest GDNF concentration at the distal end, and (4) isograft. After 6 weeks, the nerve grafts were explanted, harvested, and fixed for histologic analysis. Nerve tissue stained with the S-100, and neuroendocrine marker PGP 9.5 antibodies demonstrated a significantly increased density of nerve tissue in the GDNF-treated groups compared with the empty microsphere (control) group (P < 0.05). GDNF-treated animals with a higher concentration of GDNF in the distal portion possessed a significantly higher density of PGP 9.5 protein middle conduit part than comparison to GDNF uniform-treated animals (P < 0.05). Silk-based nerve conduits possess optimal mechanical and degradative properties, rendering them potentially useful in peripheral nerve repair. This study demonstrates that novel, porous silk fibroin--based nerve conduits, infused with GDNF in a controlled manner, represent a potentially viable conduit for Schwann cell migration and proliferation in the regeneration of peripheral nerves.     

Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve

Nerve grafts composed of basal lamina scaffolds and lacking viable Schwann cells have recently been shown to be effective in supporting axonal regeneration. As only short grafts were used in those studies, the present investigation was conducted to evaluate the ability of long acellular basal lamina nerve grafts and equivalent cellular grafts to support axonal regeneration for nerve gap repair. Cellular grafts consisted of nerve segments that had degenerated in situ for 4 weeks. Acellular grafting material consisted of similar segments that were repeatedly frozen and thawed to kill all cells prior to grafting. The results show that host axons can regenerate through the entire 4-cm length of cellular grafts but not through acellular basal lamina grafts. However, in the acellular grafts numerous axons were seen in the proximal 2-cm region. It is concluded that basal lamina grafts possess limited ability to support axonal regeneration. As in cellular grafts, viable Schwann cells appear to be important for regeneration to occur over longer distances.     

Invited review: Different conduits in peripheral nerve surgery

A considerable amount of research is being undertaken regarding the possibility of bridging loss of nerve substance with different guiding tubes, in order to improve functional outcome, reduce the surgical time, and reduce damage at donor nerve sites. A review of the literature and personal research allows us to state that: for short gaps, biological tubes (autologous veins) may give good results and also allow chemotactic attraction with selective arrangements of motor and sensory axons. Gaps longer than 1 cm do not allow tropism and are associated with failure to support axonal regrowth. Artificial biodegradable conduits still show results that are controversial; they may give good results provided that the material of which they are made is perfectly tolerated. Empty tubes, longer than 8-10 mm, besides being deprived of the chemotactic attraction, may collapse or be partially reabsorbed and replaced by scar. Probably in the near future biological or biodegradable tubes, containing lamininlike substances or muscle scaffold, will allow us to bridge increasingly large defects in nerves.     

Nerve conduits for nerve repair or reconstruction

Advances in treating peripheral nerve lesions have resulted from research in nerve regeneration and the use biomaterials as well as synthetic materials. When direct tensionless repair of peripheral nerve lesions is not possible, nerve conduits may be used to bridge digital sensory nerve gaps of ≤3 cm. Nerve autograft is the benchmark for larger, longer, mixed, or motor nerve defects. Biologic, autogenous conduits-typically veins or, rarely, arteries-have demonstrated their utility in nerve gaps <3 cm in length. Three types of bioabsorbable conduit have been approved by the US Food and Drug Administration, constructed of collagen, polyglycolic acid, or caprolactone. Caprolactone conduits have been found to be equivalent in results to autograft. Collagen conduits are next best, and polyglycolic acid conduits are functionally inferior. Further research and prospective, multicenter, large-scale trials are needed to help establish the role of synthetic, bioabsorbable conduits in peripheral nerve reconstruction.     

Experimental peripheral nerve repair: environmental control directed at the cellular level

This study recognizes recent advances in the understanding of the anatomy and physiology of peripheral nerves at the cellular level. It has reproduced study conditions originally advocated by de Medinaceli and coworkers, with modifications. Eighty-four rats were divided into three groups. Group A underwent sciatic nerve transection and standard perineurial repair. Group B nerves were frozen, severed with a vibrating blade, and reconnected by tubulization with a rubber cuff while bathed in solutions designed to inhibit Ca++-calmodulin activation, maintain colloid osmotic pressure, and mimic ambient electrolytic conditions. Group C underwent a similar procedure as group B, with the rubber cuff replaced by a polyglycolic acid mesh. All animals were randomized and evaluated functionally in terms of a sciatic index. By post-operative day 225, animals of group A recovered 37% of function, group B recovered 74%, and group C recovered 67%. Compound action potential recordings revealed a velocity recovery of 41% in group A, 70% in group B, and 81% in group C. Microscopic evaluation provided evidence for corresponding structural improvement. This new method of nerve repair is uncomplicated, relatively inexpensive, and easily adaptable to other animal models.     

Repair of lacerated peripheral nerves with nerve conduits

Peripheral nerve lesions are relatively common injuries encountered by hand surgeons. These injuries are notorious for causing significant and potentially long-standing impairment to hand function. Numerous surgical techniques with varying degrees of success have been described to treat this injury. The evolution of peripheral nerve repair has led to the development of the nerve conduit, a surgical technique that functionally bridges the gap between transected nerves. We discuss a brief history and evolution of nerve conduits and offer our preferred technique for peripheral nerve repair with a collagen nerve conduit. In addition, we offer case studies and postoperative rehabilitation goals and present early results associated with this type of repair.     

Comparison of histologic and functional recovery after peripheral nerve repair.

After repair, nerve stains of skin and subcutaneous tissue biopsies of 23 fingertips contained identifiable axons in all patients. The level of recovery was more advanced in some patients than in others, as manifested by identifiable nerve in various plexuses and receptors. Meissner's corpuscles were observed to be reinnervated in 12 of 17 patients and in 16 of 23 fingertips. The degree and level of reinnervation did not correlate with clinical testing or subjective impression of the result. The authors conclude that sensibility is the result of several factors active in the peripheral and central nervous system. Axonal regrowth is but one of these.     

几丁糖复合聚乙烯醇神经导管修复大鼠坐骨神经损

目的 径较粗,达到正常神经的直径。肌肉湿重和肌细胞截面积：A组和C组比较,差异无统计学意义(P＞0.05);A、C组明显优于B组,差异有统计学意义(P＜0.05)。组织学观察：A组和C组神经纤维数日多、大小均匀、成熟良好,B组神经纤维数目少、不均匀、髓鞘发育较差。神经示踪观察结果显示：A、B、C三组在L4～L6节段脊髓前角和背根节均可见到真蓝标记的神经元细胞,其中A组脊髓前角真蓝标记的神经元数目和C组相似,差异无统计学意义(P＞0.05),但明显优于B组,差异有统计学意义(P＜0.05)。 结论 几丁糖复合聚乙烯醇神经导管具有促进神经轴突再生的作用,有望成为自体神经的替代材料,应用于周围神经缺损的修复。     

FK 506加速周围神经损伤修复后的功能恢复

目的：探讨FK506对大鼠坐骨神经横断伤修复后肢体功能恢复的影响。方法：45只SD大鼠高位切断坐骨神经后原位缝合，术后实验组（25只）用FK506灌胃，对照组（20只）不给药，于术后第1、2、3、5个月检测术肢比目鱼肌肌湿重恢复率，小腿三头肌肌力恢复率，坐骨神经功能指数及皮层体感诱发电位（SEEP）的潜伏期，结果：实验组肢体功能恢复时间较对照组提前大约2个月。结论：FK506可加速周围神经横断伤修复后肢体功能的恢复。     

The influence of nerve conduits diameter in motor nerve recovery after segmental nerve repair

Many conduits have demonstrated potential to substitute nerve autografts; however, the influence of conduit inner diameter (ID) has never been studied as a separate parameter. This experimental study compared motor recovery after segmental nerve repair with two different ID collagen conduits: 1.5 and 2.0 mm. In addition, the conduits were analyzed in vitro to determine the variations of ID before and after hydration. Thirty rats were divided into three groups: 2.0 mm ID, 1.5 mm ID, and a control group autograft. After 12 weeks, the 1.5 mm ID group demonstrated significant increase in force (P < 0.0001) and weight (P < 0.0001) of the tibialis anterior muscle and better histomorphometry results of the peroneal nerve (P < 0.05) compared to 2.0 mm ID group; nevertheless, autograft results outperformed both conduits (P < 0.0001). Conduits ID were somewhat smaller than advertised, measuring 1.59 ± 0.03 mm and 1.25 ± 0.0 mm. Only the larger conduit showed a 6% increase in ID after hydration, changing to 1.69 ± 0.02 mm. Although autografts perform best, an improvement in motor recovery can be achieved with collagen conduits when a better size match conduit is being used. Minimal changes in collagen conduits ID can be expected after implantation. © 2014 Wiley Periodicals, Inc. Microsurgery 34:646–652, 2014.     

US Food and Drug Administration/Conformit Europe-approved absorbable nerve conduits for clinical repair of peripheral and cranial nerves

Several absorbable nerve conduits are approved by the US Food and Drug Administration (FDA) and Conformit Europe (CE) for clinical repair of peripheral and cranial nerves. Surgeons are often not aware of the different (bio)materials of these conduits when performing nerve repair. An overview of these FDA- and CE-approved absorbable nerve conduits for clinical use is presented. PubMed, MEDLINE, and the companies selling the conduits were consulted. The available FDA and CE absorbable nerve conduits for peripheral and cranial nerve repair are 2 collagen- and 2 synthetic-polyester-based conduits. The available clinical data, the price, the length, and the composition of the tube show significant differences. Based on the available data in this paper at this moment, we favor the PGA (Neurotube) nerve conduit for repair of peripheral and cranial nerve defects because of its advantages in length, price, and availability of clinical data. However, no prospective studies comparing the available nerve conduits have been published.