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Peripheral nerves convey signals between the spinal cord and the rest of the body. Peripheral nerve injury (PNI) is a challenging problem with a variety of aetiologies and symptoms. Injuries can be classified into three categories: neurapraxia, axonotmesis and neurotmesis. Axonotmesis and neurotmesis result in Wallerian degeneration of the axons distal to the site of injury. After this process is complete, damaged neurons attempt to regenerate the damaged fibre with axonal budding. Successful axonal growth relies on an intact connective tissue tunnel and the requisite signalling molecules to allow the axon to re-grow in the correct direction and re-innervate the target tissue. Without this, the axons may form a painful neuroma. To differentiate between the different grades of nerve injury special tests can be utilized including neurophysiological investigation–nerve conduction studies and electromyography (EMG). Imaging the damaged nerve with ultrasound or MRI may be useful for diagnosis and surgical planning, however investigations should not delay referral to a nerve surgeon. The aim of surgical repair in nerve injury is to re-establish continuity between the connective tissue structures of the nerve; this allows axons to elongate across the site of injury to reach the target tissue. The simplest technique is tensionless end-to-end epineural repair. In injuries where this is impossible other surgical options include nerve grafting, nerve conduits or nerve transfer.

Functional outcomes following nerve repair remain suboptimal. Scarring at the repair site is a major impediment to regeneration. A biomaterial scaffold applied around the coaptation site that decreases inflammation holds great potential in reducing scarring, enhancing axonal growth, and improving functional recovery. In this study, we evaluated the effect of a macroporous nanofiber wrap, comprised of nonwoven electrospun poly-ε-caprolactone (PCL), in improving axonal regeneration in a rat sciatic nerve cut and direct repair model. Controls consisted of conventional epineurial repair. We also evaluated our wrap against the commercially available AxoGuard wrap. At five weeks following repair, the nanofiber wrap group showed a significantly decreased intraneural macrophage invasion and collagen deposition at the repair site. This was associated with increased expression of the anti-inflammatory cytokine (IL-10), decreased expression of the pro-inflammatory cytokine (TNF-α), and a decrease in the M1:M2 macrophage phenotype ratio. These findings suggest that this nanofiber wrap, with its unique macroporosity, is modulating the inflammatory response at the repair site by polarizing macrophages towards a pro-regenerative M2 phenotype. Concomitantly, a higher number of regenerated axons was noted. At sixteen weeks, the nanofiber wrap resulted in enhanced functional recovery as demonstrated by electrophysiology, neuromuscular re-innervation, and muscle histology. When compared to the AxoGuard wrap, the nanofiber wrap showed similar inflammation at the repair site and similar nerve morphometric findings, but there was a trend towards a lower overall number of macrophages invading the wrap wall. These results demonstrate favorable outcomes of the macroporous nanofiber wrap in promoting neuroregeneration and functional recovery following nerve repair. STATEMENT OF SIGNIFICANCE: Electrospun nanofiber scaffolds, with specific fiber and pore sizes, were shown to modulate the immune response and create a regenerative environment. In this paper, we present a macroporous nanofiber wrap, made of poly-ε-caprolactone, to be applied at the coaptation site in primary nerve repair. We show that it regulates the inflammatory response at the repair site and decreases scarring/fibrosis. This results in enhanced axonal regeneration, allowing a higher number of axons to cross the suture line and reach the target muscle in a timely fashion. Functional outcomes are thus improved.

Purpose Outcomes after end-to-end epineural suture repair remain poor. Nerve wraps have been advocated to improve regeneration across repair sites by potentially reducing axonal escape and scar ingrowth; however, limited evidence currently exists to support their use. Methods Forty Lewis rats underwent median nerve division and immediate repair. Half were repaired with epineural suturing alone, and the others underwent epineural suture repair with the addition of a nerve wrap. Motor recovery was measured using weekly grip strength and nerve conduction testing for 15 weeks. Histomorphometric analyses were performed to assess intraneural collagen deposition, cellular infiltration, and axonal organization at the repair site, as well as axonal regeneration and neuromuscular junction reinnervation distal to the repair site. Results The wrapped group demonstrated significantly less intraneural collagen deposition at 5 weeks. Axonal histomorphometry, cellular infiltration, neuromuscular junction reinnervation, and functional recovery did not differ between groups. Conclusions Nerve wraps reduced collagen deposition within the coaptation; however, no differences were observed in axonal regeneration, neuromuscular junction reinnervation, or functional recovery. Clinical relevance These findings suggest that extracellular matrix nerve wraps can attenuate scar deposition at the repair site. Any benefits that may exist with regards to axonal regeneration and functional recovery were not detected in our model.

Many surgical techniques are available for the repair of peripheral nerve defects. Autologous nerve grafts are the gold standard for most clinical conditions. In selected cases, alternative types of reconstructions are performed to fill the nerve gap. Non-nervous autologous tissue-based conduits or synthetic ones are alternatives to nerve autografts. Allografts represent another new field of interest. Decision making in the treatment of nerve defects is based on timing of referral, level of the injury, type of lesion, and size of any gap. This review focuses on current clinical practice, influenced by the numerous new experimental researches.

Background Tissue processing to create immunotolerant nerve allograft removes neurosupportive cells. Few strategies have been described for implanting new cells into the graft to support axonal regeneration. New method Micropuncture of the nerve allograft surface combined with immersion into a pressurized cell-rich solution to potentiate the introduction of viable Schwann cells (SC) into processed nerve allograft. Allografts were used to repair rodent sciatic nerve defects. At 3, 7, and 21 days, grafts were harvested, stained for SCs, and analyzed using total cross sectional area (CSA) occupied by SCs to quantify SC presence. Results At days 3 and 7, SC CSA was significantly greater for the injection group compared to all other groups. At day 21, SC CSA for the injection group (0.2252% ± 0.2730) was significantly greater compared to following groups: pressurized-punctured (0.0653% ± 0.0934), nonpressurized-nonpunctured (0.0607% ± 0.0709), punctured-control (0.0246% ± 0.0398), and nonpunctured-control (0.0126% ± 0.0151). A significant decrease in percent CSA occupied by SCs from day 3 to day 21 was noted in nonpressurized-punctured group (p = 0.0106), pressurized-nonpunctured group (p = 0.0477), and injection group (p = 0.0010). Comparison with existing method(s) Most studies have used small caliber hypodermic needles to inject the cells into grafts. Conclusions Despite a presumed decrease in cell viability over the three weeks of the study, the large initial inoculum achieved by injection technique results in higher levels of final SC seeding in acellular nerve allograft compared with bathing techniques with or without micropuncture or pressurization.

Employment of regenerative properties of cells at the service of nerve repair has been initiated during recent decades. Effects of local transplantation of bone marrow-derived mast cells on peripheral nerve regeneration were studied using a rat sciatic nerve transection model.A 10-mm sciatic nerve defect was bridged using a conduit chitosan-based hybrid conduit filled with BMMCs in BMMC group. In positive control group (Pos), the conduit was filled with phosphate-buffered saline alone. The regenerated nerve fibers were studied within 12 weeks after surgery. In sham-operated group, the sciatic nerve was only exposed and manipulated. In negative control (Neg) a 10-mm sciatic nerve defect was created and the nerve stumps were sutured to the adjacent muscles. The regenerated nerve fibers were studied functionally, biomechanically, histologically and immunohiscochemically.Functional and biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to Pos group (p0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in Pos group (p0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in Pos group.BMMCs transplantation could be considered as a readily accessible source of cells that could improve functional recovery of transected sciatic nerve.

Alternatives to nerve autograft have been invented and approved for clinical use. The reported outcomes of these alternatives in mixed motor nerve repair in humans are scarce and marked by wide variabilities. The purpose of our Current Concepts review is to provide an evidence-based overview of the effectiveness of nerve conduits and allografts in motor and mixed sensory/motor nerve reconstruction. Nerve graft substitutes have good outcomes in mixed/motor nerves in gaps less than 6 mm and internal diameters between 3 and 7 mm. There is insufficient evidence for their use in larger-gap and -diameter nerves; the evidence remains that major segmental motor or mixed nerve injury is optimally treated with a cabled nerve autograft.

Background The gold standard in the primary and secondary treatment for a nerve gap reconstruction is still autologous nerve grafting. Over short distances, application of nerve conduits can effectively solve the problems of limited availability of donor tissue, sacrifice of a functional nerve, and possible neuroma formation of autologous nerve grafting. There are a variety of non-absorbable and absorbable nerve conduits. Method and Results The 21-years old patient was a war victim in Syria and suffered a shooting trauma of the left thigh two years ago. Nerve reconstruction of the sciatic nerve with a giant nerve tube was performed 9 months after the trauma. Due to the young age of the patient we decide to conduct an exploration and possibly autologous nerve transplantation 2 years after primary surgery. Intraoperatively we found an intubation tube used as a non-bioabsorbable nerve tube including no nerval tissue. Conclusion This case describes probably the largest nerve tube ever but it also reflects the improvisation of war surgeons under limited circumstances in order to provide a satisfactory medical care during war times.

Rat models of complete and partial injuries are the most frequently used models for analysis of the cellular and molecular processes of nerve regeneration and axon sprouting. Studies of nerve regeneration and axon sprouting after complete and partial nerve injuries, respectively, are reviewed. Special consideration is made of the peripheral nerves chosen for the studies and the outcome measures that were utilized in the studies. The studies have made important contributions to our knowledge of the degenerative and regenerative processes that occur after the peripheral nerve injuries, why functional recovery is frequently compromised after delayed surgery, the positive effects of neurotrophic factors on nerve regeneration after delayed nerve repair or after insertion of autografts between transected nerve, and how axon regeneration may be accelerated by brief periods of electrical stimulation and/or by administration of androgens.

Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand.

Poor functional outcomes are frequent after peripheral nerve injuries despite the regenerative support of Schwann cells. Motoneurons and, to a lesser extent, sensory neurons survive the injuries but outgrowth of axons across the injury site is slow. The neuronal regenerative capacity and the support of regenerating axons by the chronically denervated Schwann cells progressively declines with time and distance of the injury from the denervated targets. Strategies, including brief low-frequency electrical stimulation that accelerates target reinnervation and functional recovery, and the insertion of cross-bridges between a donor nerve and a recipient denervated nerve stump, are effective in promoting functional outcomes after complete and incomplete injuries.

The superficial peroneal nerve is now known as the superficial fibular nerve (SFN). Identification and treatment of entrapment of the SFN are important topics of discussion for foot and ankle surgeons, because overlooking the diagnosis can lead to permanent nerve damage. With the proper tools and skills, surgeons are able to help patients with symptomatic SFN entrapment, patients who often present in some degree of desperation, with the peripheral nerve surgeon as a last resort.

Neurotrophic factors and peripheral nerves are known to be good substrates for bridging CNS trauma. The involvement of fibroblast growth factor-2 (FGF-2) activation in the dorsal root ganglion (DRG) was examined following spinal cord injury in the rat. We evaluated whether FGF-2 increases the ability of a sciatic nerve graft to enhance neuronal plasticity, in a gap promoted by complete transection of the spinal cord. The rats were subjected to a 4 mm-long gap at low thoracic level and were repaired with saline (Saline or control group, n = 10), or fragment of the sciatic nerve (Nerve group, n = 10), or fragment of the sciatic nerve to which FGF-2 (Nerve + FGF-2 group, n = 10) had been added immediately after lesion. The effects of the FGF-2 and fragment of the sciatic nerve grafts on neuronal plasticity were investigated using choline acetyl transferase (ChAT)-immunoreactivity of neurons in the dorsal root ganglion after 8 weeks. Preservation of the area and diameter of neuronal cell bodies in dorsal root ganglion (DRG) was seen in animals treated with the sciatic nerve, an effect enhanced by the addition of FGF-2. Thus, the addition of exogenous FGF-2 to a sciatic nerve fragment grafted in a gap of the rat spinal cord submitted to complete transection was able to improve neuroprotection in the DRG. The results emphasized that the manipulation of the microenvironment in the wound might amplify the regenerative capacity of peripheral neurons

An increasing number of biomaterial nerve guides has been developed that await direct comparative testing with the 'gold-standard' autologous nerve graft in functional repair of peripheral nerve defects. In the present study, 20 mm rat sciatic nerve defects were bridged with either a collagen-based micro-structured nerve guide (Perimaix) or an autologous nerve graft. Axons regenerated well into the Perimaix scaffold and, the majority of these axons grew across the 20 mm defect into the distal nerve segment. In fact, both the total axon number and the number of retrogradely traced somatosensory and motor neurons extending their axons across the implant was similar between Perimaix and autologous nerve graft groups. Implantation of Schwann cell-seeded Perimaix scaffolds provided only a beneficial effect on myelination within the scaffold. Functional recovery supported by the implanted, non-seeded Perimaix scaffold was as good as that observed after the autologous nerve graft, despite the presence of thinner myelin sheaths in the Perimaix implanted nerves. These findings support the potential of the Perimaix collagen scaffold as a future off-the-shelf device for clinical applications in selected cases of traumatic peripheral nerve injury.

The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration.

Summary Background Multiple-branch reconstruction is required in order to attain facial reanimation for extensive facial nerve defects. We previously reported that end-to-side nerve grafting, with the use of a single nerve graft for defect reconstruction, was easy to perform. We have also demonstrated the efficacy of end-to-side nerve suture of the recipient nerve to the donor graft nerve, in experimental rat models and clinical cases. The regenerating axons, which extended into the nerve graft, were "distributed" to multiple recipient nerves via end-to-side nerve-suture sites. Methods Thirty-two patients who underwent facial nerve reconstruction (five to 10 branches) had a single sural nerve graft coapted to the proximal stump of the facial nerve in an end-to-end manner, followed by end-to-side nerve suture of the recipient nerve stumps to the side of the nerve graft. In 19 patients who were expected to undergo postoperative radiotherapy and/or chemotherapy, the distal end of the graft was connected to the side of the hypoglossal nerve for "axonal supercharging," to enhance the recovery of the facial muscles. Results Initial facial movements were noted at 5–12 months postoperatively, and good recovery (House–Brackmann grade III/IV) was observed during long-term follow-up in most patients. Conclusion End-to-side nerve suture of the recipient nerve stumps to the nerve graft requires less graft nerve material and less technical mastery to reconstruct multiple branches of the facial nerve. We also described the concept of "axonal supercharging," namely the connection of double-donor neural sources to the graft, and "axonal distribution," namely the reinnervation of multiple recipient nerve stumps connected to the graft in an end-to-side manner. This combination of axonal supercharging and distribution can be a useful option in facial nerve reconstruction.

This article provides an overview of the management of traumatic peripheral nerve injuries. It examines the basic pathophysiology of peripheral nerve injuries, along with the clinical presentation, diagnostic work-up, and treatment options and outcomes for the various classifications of traumatic peripheral nerve injuries.

We had previously reported that small gap neurorrhaphy by scissoring and sleeve-jointing epineurium could enhance the rate and quality of peripheral nerve regeneration. To date, local implantation and systemic delivery of bone marrow mesenchymal stem cells (BMSCs) have been routinely used in nerve tissue engineering, but they each have some intrinsic limitations. We hypothesised that targeted muscular administration of BMSCs capable of reaching the damaged nerve would be advisable. Here, we investigated the therapeutic efficacy of transplantation of BMSCs through targeted muscular injection with small gap neurorrhaphy by scissoring and sleeve-jointing epineurium on repairing peripheral nerve injury in a rat model. One week after a rat model of peripheral nerve injury was established by small gap neurorrhaphy, thirty-six Sprague-Dawley rats were randomly divided into three groups (n=12): the intramuscular injection of BMSCs group (IM), the intravenous injection of BMSCs group (IV) and the intramuscular injection of phosphate-buffered solution group (PBS). The process of the nerve regeneration was assayed functionally and morphologically. The results indicated that compared to the IV-treated and PBS-treated groups, the targeted muscular injection therapy resulted in much more beneficial effects, as evidenced by increases in the sciatic function index, nerve conduction velocity, myelin sheath thickness and restoration rate of gastrocnemius muscle wet weight. In conclusion, the combination therapy of small gap neurorrhaphy and BMSC transplantation through targeted muscular injection can significantly promote the regeneration of peripheral nerve and improve the nerve's functional recovery, which may help establish a reliable approach for repairing peripheral nerve injury.

The standard treatment of peripherical nerve injuries with substance gap is to introduce the nerve free extremes in a biodegradable tube which, as a biocamera, allows the continuity of the nerve, promote the neuroconduction and save the lesion from the surrounding fibrosis. However, this procedure has not any direct effect on the neuroregeneration nor to resolve high severe lesions. The mesenchymal stem cells (MSC) can derivate "in vitro" in different lineages, including Schwann cells. Different studies have shown MSC can promote the nerve regeneration in rodents, dogs and primates. Moving to the human clinical application requires the procedure standardization, including the optimal cell dose which we have to use. In the sheep model animal we performed a study of 1 cm. nerve section-ressection and repair with a Neurolac™ biocamera, in whose gap we applied between 30 to 50×10(6) MSC from cancellous bone, all of them selected and cultured with GMP procedures. The results were compared with controls (saline serum ± platelet-rich plasma). We used radial nerve (sensitive) and tibial nerve (motor) from 7 sheep. In the first step we performed the surgical lesion and bone marrow aspiration, and in 3 weeks we performed the surgical repair. 3 sheep were sacrificed in 3 months, and 4 sheep in 6 months. In all surgeries we performed a neurophysiological register. When we obtained the tissue samples, we performed an histological, immunohistiquimical and morphometrical study. The recovery percentage was defined comparing the axonal density from the proximal and distal lesion margins. The 3 months samples results were wrong. In 6 months samples results we observed a significative myelined nervous fibers and conduction increasing, in front of controls, both radial and tibial nerves. These results suggest the MSC application in biodegradable scaffold in nerve injuries promotes good results in terms of regeneration and functional recovery.

A distal median to ulnar nerve transfer for timely restoration of critical intrinsic muscle function is possible in isolated ulnar nerve injuries but not for combined ulnar and median nerve injuries. We used a distal nerve transfer to restore ulnar intrinsic function in the case of a proximal combined median and ulnar nerve injury. Transfer of the nonessential radial nerve branches to the abductor pollicis longus, extensor pollicis brevis, and extensor indicis proprius to the motor branch of the ulnar nerve was performed in a direct end-to-end fashion via an interosseous tunnel. This method safely and effectively restored intrinsic function before terminal muscle degeneration.

A tension-free coaptation is a key factor for the successful outcome of any nerve repair. A variety of host factors influence the outcome of digital nerve repair more than the type of repair per se. Although autologous graft remains the reference standard for reconstruction of any critical digital nerve defect, allografts and conduits have assumed an increasing role.

Restoring neurological function to a damaged peripheral nerve separated by a gap requires axon regeneration (1) across the gap, no matter its length, and then (2) through the distal portion of the nerve, regardless of the time between the trauma and repair, and irrespective of animal or patient age. Sensory nerve grafts, the clinical "gold standard", and most alternative techniques for bridging nerve gaps, promote reliable axon regeneration only across nerve gaps2cm in length, and with few axons regenerating when nerve repairs are performed2 months post-trauma or for patients20 years of age. Three novel nerve repair techniques are discussed that induce axon regeneration and neurological recovery clinically under conditions where other techniques are ineffective: for nerve gaps up to cm long, repairs performed as late as 3.25 years post-trauma, and for patients up to 58 years old. The mechanisms by which these techniques may work are discussed. Although these techniques provide significant improvements in the extents of axon regeneration and neurological recovery, more extensive and reliable clinical recovery of neurological function is needed and will probably require the simultaneous application of multiple techniques.

Previous work has shown that infusion of skin-derived precursors pre-differentiated into Schwann cells (SKP-SCs) can remyelinate injured and regenerating axons, and improve indices of axonal regeneration and electrophysiological parameters in rodents. We hypothesized that SKP-SC therapy would improve behavioral outcomes following nerve injury repair and tested this in a pre-clinical trial in 90 rats. A model of sciatic nerve injury and acellular graft repair was used to compare injected SKP-SCs to nerve-derived Schwann cells or media, and each was compared to the gold standard nerve isograft repair. In a second experiment, rats underwent right tibial nerve transection and received either acute or delayed direct nerve repair, with injections of either 1) SKP-SCs distal to the repair site, 2) carrier medium alone, or 3) dead SKP-SCs, and were followed for 4, 8 or 17weeks. For delayed repairs, both transected nerve ends were capped and repaired 11weeks later, along with injections of cells or media as above, and followed for 9 additional weeks (total of 20weeks). Rats were serially tested for skilled locomotion and a slip ratio was calculated for the horizontal ladder-rung and tapered beam tasks. Immediately after nerve injury and with chronic denervation, slip ratios were dramatically elevated. In the GRAFT repair study, the SKP-SC treated rats showed statistically significant improvement in ladder rung as compared to all other groups, and exhibited the greatest similarity to the sham controls on the tapered beam by study termination. In the ACUTE repair arm, the SKP-SC group showed marked improvement in ladder rung slip ratio as early as 5weeks after surgery, which was sustained for the duration of the experiment. Groups that received media and dead SKP-SCs improved with significantly slower progression. In the DELAYED repair arm, the SKP-SC group became significantly better than other groups 7weeks after the repair, while the media and the dead SKP-SCs showed no significant improvement in slip ratios. On histomorphometrical analysis, SKP-SC group showed significantly increased mean axon counts while the percent myelin debris was significantly lower at both 4 and 8weeks, suggesting that a less inhibitory micro-environment may have contributed to accelerated axonal regeneration. For delayed repair, mean axon counts were significantly higher in the SKP-SC group. Compound action potential amplitudes and muscle weights were also improved by cell therapy. In conclusion, SKP-SC therapy improves behavioral recovery after acute, chronic and nerve graft repair beyond the current standard of microsurgical nerve repair.

Peripheral nerve surgery represents a broad field of pathologic conditions, medical specialties, and anatomic regions of the body. Anatomic understanding of hierarchical nerve structure and the peripheral nervous system aids diagnosis and management of nerve lesions. Many peripheral nerves coalesce into organized arrays, including the cervical, brachial, and lumbosacral plexuses, controlling motor and sensory functions of the trunk and extremities. Individual or groups of nerves may be affected by various pathologic conditions, including trauma, entrapment, tumor, or iatrogenic damage. Current research efforts focus on enhancing the peripheral nerve regenerative process by targeting Schwann cells, nerve growth factors, and nerve allografts.

Major peripheral nerve injuries in the upper extremities can result in significant morbidity. Understanding the pathophysiology of these injuries aids in the assessment and planning of appropriate treatment. With limited nerve mobilization, tension-free repairs can often be performed using sutures, fibrin glue, or nerve connectors. Acellular allograft and autograft reconstruction are better for bridging any gaps greater than a few millimeters. Adherence to proper principles of nerve repair improves the chances of achieving a favorable result, although in general these injuries portend a guarded prognosis.

Peripheral nerve injuries requiring surgery can be repaired by autograft, the clinical "gold standard", allograft, or nerve conduits. Most published clinical studies show the effectiveness of nerve conduits in small size defects in sensory nerves. Many preclinical studies suggest that peripheral nerve regeneration through conduits can be enhanced and repair lengths increased with the use of a biomaterial filler in the conduit lumen. We have previously shown that a luminal hydrogel filler derived from human hair keratin (HHK) can improve electrophysiological and histological outcomes in mouse, rabbit, and non-human primate nerve injury models, but insight into potential mechanisms has been lacking. Based on the premise that a keratin biomaterial (KOS) hydrogel provides an instantaneous structural matrix within the lumen, the current study compares the cellular behavior elicited by KOS hydrogel to Matrigel (MAT) and saline (SAL) conduit fillers in a 1 cm rat sciatic nerve injury model at early stages of regeneration. While there was little difference in initial cellular influx, the KOS group showed earlier migration of dedifferentiated Schwann cells (SC) from the proximal nerve end compared to the other groups. The KOS group also showed faster SC dedifferentiation and myelin debris clearance, and decreased macrophage infiltration during Wallerian degeneration of the distal nerve tissue.

The gold standard in surgical management of a peripheral nerve gap is currently autologous nerve grafting. This confers patient morbidity and increases surgical time therefore innovative experimental strategies towards engineering a synthetic nerve conduit are welcome. We have developed a novel synthetic conduit made of poly ε-caprolactone (PCL) that has demonstrated promising peripheral nerve regeneration in short-term studies. This material has been engineered to permit translation into clinical practice and here we demonstrate that histological outcomes in a long-term in vivo experiment are comparable with that of autologous nerve grafting. A 1cm nerve gap in a rat sciatic nerve injury model was repaired with a PCL nerve conduit or an autologous nerve graft. At 18 weeks post surgical repair, there was a similar volume of regenerating axons within the nerve autograft and PCL conduit repair groups, and similar numbers of myelinated axons in the distal stump of both groups. Furthermore, there was evidence of comparable re-innervation of end organ muscle and skin with the only significant difference the lower wet weight of the muscle from the PCL conduit nerve repair group. This study stimulates further work on the potential use of this synthetic biodegradable PCL nerve conduit in a clinical setting.

Purpose Nerve repair after a segmental defect injury remains a challenge for surgeons. Fibrin glue can be used to expedite surgical procedures and maintain proper nerve spatial orientation to potentially optimize recovery, yet surgeons hesitate to use it owing to concerns about fibrin's inhibiting regeneration and increasing scar formation. The purpose of these experiments was to evaluate whether fibrin glue impedes nerve regeneration. Methods A critical-size defect of 10 mm was created in 32 Sprague-Dawley rats with 4 different forms of repair: a collagen type-I conduit (n = 8), a collagen type-I conduit filled with fibrin glue (n = 8), an autologous nerve graft (n=8), and an autologous nerve graft with fibrin glue (n = 8). Behavioral tests, including sciatic functional indices, were used to evaluate functional recovery. Neurophysiology, immunohistochemistry, and nerve morphometry were used to critically analyze nerve regeneration. Results Multiple outcome parameters for nerve regeneration, remyelination, behavior, and electrophysiology were used to determine that the addition of fibrin did not influence recovery for the autograft groups. Similarly, within the conduit group, behavioral tests showed comparable functional recovery and indistinguishable results in compound motor action potential and nerve morphometry. Immunohistochemistry revealed identical degrees of Wallerian degeneration and scarring between conduit groups. Conclusions The addition of fibrin to either the conduit or the autograft group did not result in any meaningful differences in recovery. Our data demonstrate that fibrin glue does not impede nerve regeneration or functional recovery after surgical repair of a segmental nerve defect in a rat model. Clinical relevance The clinical use of fibrin glue as an adjunct with peripheral nerve repair may be considered safe because it does not impair nerve regeneration with critical size defects in an animal model.

In cases of complex neuromuscular defects, finding the proximal stump of a transected nerve in order to restore innervation to damaged muscle is often impossible. In this study we investigated whether a neighboring uninjured nerve could serve as a source of innervation of denervated damaged muscle through a biomaterial-based nerve conduit while preserving the uninjured nerve function. Tubular nerve conduits were fabricated by electrospinning a polymer blend consisting of poly(ε-caprolactone) (PCL) and type I collagen. Using a rat model of common peroneal injury, the proximal end of the nerve conduit was connected to the side of the adjacent uninjured tibial branch (TB) of the sciatic nerve after partial axotomy, and the distal end of the conduit was connected to the distal stump of the common peroneal nerve (CPN). The axonal continuity recovered through the nerve conduit at 8 weeks after surgery. Recovery of denervated muscle function was achieved, and simultaneously, the donor muscle, which was innervated by the axotomized TB also recovered at 20 weeks after surgery. Therefore, this end-to-side neurorrhaphy (ETS) technique using the electrospun PCL/collagen conduit appears to be clinically feasible and would be a useful alternative in instances where autologous nerve grafts or an adequate proximal nerve stump is unavailable.

Functional motor recovery after peripheral nerve injury is predominantly determined by the time to motor end plate reinnervation and the absolute number of regenerated motor axons that reach target. Experimental models have shown that axonal regeneration occurs across a supercharged end-to-side (SETS) nerve coaptation. In patients with a recovering proximal ulnar nerve injury, a SETS nerve transfer conceptually is useful to protect and preserve distal motor end plates until the native axons fully regenerate. In addition, for nerve injuries in which incomplete regeneration is anticipated, a SETS nerve transfer may be useful to augment the regenerating nerve with additional axons and to more quickly reinnervate target muscle. We describe our technique for a SETS nerve transfer of the terminal anterior interosseous nerve (AIN) to the pronator quadratus muscle (PQ) end-to-side to the deep motor fascicle of the ulnar nerve in the distal forearm. In addition, we describe our postoperative therapy regimen for these transfers and an evaluation tool for monitoring progressive muscle reinnervation. Although the AIN-to-ulnar motor group SETS nerve transfer was specifically designed for ulnar nerve injuries, we believe that the SETS procedure might have broad clinical utility for second- and third-degree axonotmetic nerve injuries, to augment partial recovery and/or "babysit" motor end plates until the native parent axons regenerate to target. We would consider all donor nerves currently utilized in end-to-end nerve transfers for neurotmetic injuries as candidates for this SETS technique.

Purpose Although the end-to-side nerve repair technique has been used clinically, it has not yet produced consistent motor and sensory recovery in patients. The aim of this study was to investigate whether end-to-side double nerve grafts display more axonal regeneration compared with a single nerve graft in a rat lower limb preparation. Methods The lower limbs of 96 Wister rats were used in experiments comparing single and double end-to-side nerve grafts. Left peroneal nerves were harvested and grafted between the right peroneal and tibial nerves. A single graft was attached end-to-side to the peroneal and tibial nerves through an epineural window (single graft group, n=24). Two grafts were performed in the same manner in the double graft group (n = 24). The peroneal nerve was exposed in positive controls (n = 24) and no graft was performed in negative controls (n = 24). We recorded action potentials and moist weights of the left tibialis anterior muscle at each time point. Fluoro-Gold-labeled (Fluorochrome, Denver, CO) dorsal root ganglion neurons from L1 to L6 were counted using fluorescence microscopy and compared among the 4 groups. Results In both single and double groups, the amplitude and the tibialis anterior muscle weight increased significantly compared with negative controls but remained lower than those measured in positive controls. There was no significant difference between single and double groups. In Fluoro-Gold-labeled neurons, there was also no significant difference between single and double groups. Conclusions The study showed that regeneration of motor and sensory nerve fibers was possible using 2 end-to-side nerve grafts. However, there was no significant difference between single and double grafts. This might suggest a therapeutic limitation of nerve transplants using 2 end-to-side nerve grafts. Clinical relevance Double end-to-side repair attracts both motor and sensory axons, and this results in a medium degree of recovery of function; however, double end-to-side nerve grafting does not appear to offer any advantage over a single end-to-side graft.

Over the past few years, my group has been investigating the effects of different parameters of electrical stimulation on nerve regeneration of a 10-mm gap of rat sciatic nerve created between the proximal and distal nerve stumps, which were sutured into silicone rubber chambers. In this review, I will introduce our work and share our experience with investigators who are interested in the fields of nerve regeneration and biomedical engineering.

Summary Background Nerve reconstruction following lower-extremity nerve injuries usually leads to worse outcomes in comparison with upper-extremity injuries due to the long distances of nerve regeneration. This study was performed to consider the clinical application of distal nerve transfer for the treatment of long gaps of the tibial nerve (TN) and in established compartment syndrome. It aimed to determine the anatomic suitability of transferring the sural nerve (SN) in combination with the superficial peroneal nerve (SPN) to the TN at the level of the tarsal tunnel for restoration of plantar sensation. Methods Nine fresh above-knee amputated limbs were dissected with the aid of loupe magnification. We focussed on the detailed anatomy of the course of the SN and the SPN from its emergence proximally at the knee level to the foot. Two different regions, suprafascial and subfascial, were described for each nerve. The maximum length of dissection and the length of the nerves in each region were measured. In all dissections, we assessed the feasibility of directly transferring the SN and SPN to the TN at the level of the tarsal tunnel. Results The average length of the course of the SN was 20.6 cm (SD ± 2.3 cm) subfascially and 16.4 cm (SD ± 0.9 cm) suprafascially. For the SPN, the average length was 19.4 cm (SD ± 1.9 cm) subfascially and 18 cm (SD ± 2.5 cm) suprafascially. The point of emergence of the nerve from the subfascial course to the suprafascial course was defined as the pivot point for its transfer to the TN. Both the SN and the SPN reached the TN comfortably at the level of the tarsal tunnel, allowing direct co-aptation. Conclusion Distal nerve transfer using the SN in combination with the SPN is an anatomically reliable procedure, being a potential alternative to the use of nerve grafts in reconstruction of long gaps of the TN. In addition, selected patients with compartment syndrome may also benefit from this transfer to restore plantar sensation.

Neurotrophic factors may be used to improve the growth and repair of injured peripheral nerves. In this study we determined the effectiveness of recombinant human growth hormone on peripheral nerve injury in the Wistar rat. The ulnar nerve of the rat was sectioned and its proximal and distal ends were sutured to either end of a silastic tube, with the aim of encouraging regeneration through the tube. 32 ulnar nerve specimens were randomized into two groups: 18 nerves regenerating under the influence of recombinant growth hormone, and 14 nerves regenerating in its absence. The study was performed over a period of 8 weeks and progression of regeneration was assessed with regular surface electroneurography every 1-2 weeks after surgery. In the group receiving recombinant growth hormone, it comprised a significant improvement in the recovery of conduction velocity, and a more gradual increase in the amplitude of motor potential from the fifth week onwards was observed. Histological analysis of study specimens in the recombinant hormone group revealed an improved architecture of the regenerating nerve, a greater density of nerve fibers, and increased myelination with a lesser degree of endoneural fibrosis. Our work demonstrates the positive effect of the administration of recombinant human growth hormone in obtaining significantly improved conduction velocities, and a greater improvement in nerve regeneration from the fifth week of monitoring when compared to the control group. Histological analysis in the group receiving hormone showed acceptable degree of myelination with little granulation tissue and fibrosis.

The transition between the central (CNS) and peripheral nervous system (PNS) in cranial and spinal nerve roots, referred to here as the CNS-PNS border, is of relevance to nerve root disorders and factors that affect peripheral-central regeneration. Here, this border is described in the cat cochlear nerve using light microscopical sections, and scanning electron microscopy of the CNS-PNS interfaces exposed by fracture of the nerve either prior to or following critical point drying. The CNS-PNS border represents an abrupt change in type of myelin, supporting elements, and vascularization. Because central myelin is formed by oligodendrocytes and peripheral myelin by Schwann cells, the myelinated fibers are as a rule equipped with a node of Ranvier at the border passage. The border is shallower and smoother in cat cochlear nerve than expected from other nerves, and the borderline nodes are largely in register. The loose endoneurial connective tissue of the PNS compartment is closed at the border by a compact glial membrane, the mantle zone, of the CNS compartment. The mantle zone is penetrated by the nerve fibers, but is otherwise composed of astrocytes and their interwoven processes like the external limiting membrane of the brain surface with which it is continuous. The distal surface of the mantle zone is covered by a fenestrated basal lamina. Only occasional vessels traverse the border. From an anatomical point of view, the border might be expected to be a weak point along the cochlear nerve and thus vulnerable to trauma. In mature animals, the CNS-PNS border presents a barrier to regrowth of regenerating nerve fibers and to invasion of the CNS by Schwann cells. An understanding of this region in the cochlear nerve is therefore relevant to head injuries that lead to hearing loss, to surgery on acoustic Schwannomas, and to the possibility of cochlear nerve regeneration.

Animal models of nerve compression, crush, and transection injuries of peripheral nerves have been subject to extensive study in order to understand the mechanisms of injury and axon regeneration and to investigate methods to promote axon regeneration and improve functional outcomes following nerve injury. Six outcome measures of regenerative success including axon and neuron counts, muscle and motor unit contractile forces, and behavior are reviewed in the context of nerve injury types, crush, transection and nerve repair by direct coaptation, or transection and repair via a nerve graft or conduit. The measures are evaluated for sciatic, tibial, common peroneal, femoral, single nerve branches such as the soleus nerve, and facial nerves. Their validity is discussed in the context of study objectives and the nerve branch. The case is made that outcome measures of axon counts and muscle contractile forces may be valid during the early phases of axon regeneration when regenerating sprouts emerge asynchronously from the proximal nerve stump and regenerate towards their denervated targets. However, care must be taken especially when experimental interventions differentially affect how many neurons regenerate axons and the number of axons per neuron that sprout from the proximal nerve stumps. Examples of erroneous conclusions are given to illustrate the need for researchers to ensure that the appropriate outcome measures are used in the evaluation of the success of peripheral nerve regeneration.

Peripheral nerve injuries affect all age groups and can be devastating to patients. A timely repair and thorough exam both preoperatively and intraoperatively can help increase the chances of a successful outcome. The technical aspects of peripheral nerve injury evaluation and repair must take into account the unique anatomy and function of the nervous system. Proper microsurgical techniques such as tension-free repair are a critical aspect of the repair process. Nerve grafts, conduits, and biotherapies are all viable ways to increase the odds of a meaningful repair. Proper immobilization, mobilization, and a targeted rehabilitation protocol are also important.

Although autologous nerve graft is still the first choice strategy in nerve reconstruction, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to improve nerve regeneration. Nerve fibrin conduits were seeded with various cell types: primary Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC). Two further control groups were fibrin conduits without cells and autografts. Conduits were used to bridge a 1 cm rat sciatic nerve gap in a long term experiment (16 weeks). Functional and morphological properties of regenerated nerves were investigated. A reduction in muscle atrophy was observed in the autograft and in all cell-seeded groups, when compared with the empty fibrin conduits. SC showed significant improvement in axon myelination and average fiber diameter of the regenerated nerves. dASC were the most effective cell population in terms of improvement of axonal and fiber diameter, evoked potentials at the level of the gastrocnemius muscle and regeneration of motoneurons, similar to the autografts. Given these results and other advantages of adipose derived stem cells such as ease of harvest and relative abundance, dASC could be a clinically translatable route towards new methods to enhance peripheral nerve repair.

The 10 mm rat sciatic nerve defect model is commonly used to investigate new strategies to improve functional recovery with segmental nerve defects. However, a lack of standardization makes comparisons between studies difficult. The present study aims to evaluate a standardized experimental model that can minimize the number of animals required for obtaining valid results and simulates a current treatment for human peripheral nerve injury defects. Eighteen cadaveric Sprague-Dawley rats were utilized in the anatomic arm of the study and 18 living Sprague-Dawley rats were used in the experimental arm. The results from the cadaveric study allowed us to create an ipsilateral, three-cable autologous sural nerve graft technique in the rat. This repair construct was evaluated with functional and histomorphometric analysis of nerve regeneration. The results support functional recovery of the sciatic nerve in all grafted animals. The use of an ipsilateral cabled sural nerve graft technique in the rat sciatic nerve defect model is a viable control group that utilizes a single incision, incurs minimal morbidity, and maintains muscle attachments. We conclude that this rat model can be used in various experimental trials in the field of peripheral nerve regeneration.

Oral and maxillofacial surgeons caring for patients who have sustained a nerve injury to a branch of the peripheral trigeminal nerve must possess a basic understanding of the response of the peripheral nerves to trauma. The series of events that subsequently take place are largely dependent on the injury type and severity. Regeneration of the peripheral nerve is possible in many instances and future manipulation of the regenerative microenvironment will lead to advances in the management of these difficult injuries.

Objective The aim of the present study is to evaluate motor and sensory results obtained after reconstruction of peripheral nerve injuries in the forearm, using silicone tubes. Methods A series of 16 injuries of forearm nerves (7 median, 7 ulnar, 1 radial sensory branch, 1 dorsal ulnar cutaneous branch) repaired with use of direct neurorraphy through a silicon tube were retrospectively studied. Eleven patients suffered associated arterial and tendinous injuries. Secondary nerve repair was performed in 3 cases and primary repair in 13, two of them in the context of re-implant of the upper limb. The series was evaluated using the functional scale described by Chanson. Results At a mean follow-up of 24 months, and having 2 cases excluded due to isolated injury of sensory branches, we obtained a 64% of good or excellent results, 28% of satisfactory results and 1 bad result. The tube was removed in 6 cases; 4 due to palpable painless tumour in the site of insertion, a case with compression symptoms after complete nerve function restoration and another that showed herniation of the stumps. In 5 cases the macroscopic restoration of the nerve was verified at the time of tube removal. Conclusion The use of silicone tubes in the reconstruction of acute, subacute and chronic nerve injuries in the forearm seems to give good results in most of the cases, with macroscopic anatomy restitution of the nerve and good functional recovery.

Autologous nerve grafts have been the 'gold standard' for treatment of peripheral nerve defects that exceed the critical gap length. To address issues of limited availability of donor nerves and donor site morbidity, we have fabricated chitosan conduits and seeded them with bone marrow stromal cell (BMSC)-derived Schwann cells as an alternative. The derived Schwann cells used were checked for fate commitment. The conduits were tested for efficacy in bridging the critical gap length of 12 mm in sciatic nerves of adult rats. By three months post-operation, mid-shank circumference, nerve conduction velocity, average regenerated myelin area, and myelinated axon count, in nerves bridged with BMSC-derived Schwann cells were similar to those treated with sciatic nerve-derived Schwann cells (p > 0.05) but significantly higher than those bridged with PBS-filled conduits (p < 0.05). Evidence is thus provided in support of the use of chitosan conduits seeded with BMSC-derived Schwann cells to treat critical defects in peripheral nerves. This provides the basis to pursue BMSC as an autologous source of Schwann cells for transplantation therapy in larger animal species.

Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. Biosynthetic neural conduits could be an alternative treatment strategy in such injuries. The present study investigates the long-term effects of a tubular fibrin conduit on neuronal regeneration, axonal sprouting and recovery of muscle weight following peripheral nerve injury and repair in adult rats. Sciatic axotomy was performed proximally in the thigh to create a 10-mm gap between the nerve stumps. The injury gap was bridged by using a 14-mm-long fibrin glue conduit, entubulating 2 mm of the nerve stump at each end. A reversed autologous nerve graft was used as a control. The regenerative response from sensory and motor neurones was evaluated following retrograde labelling with Fast Blue fluorescent tracer. In control experiments, at 16 weeks following peripheral nerve grafting, 5184 (±574 standard error of mean (SEM)) sensory dorsal root ganglion neurones and 1001 (±37 SEM) spinal motor neurones regenerated across the distal nerve-graft interface. The fibrin conduit promoted regeneration of 60% of sensory neurones and 52% of motor neurones when compared to the control group. The total number of myelinated axons in the distal nerve stump in the fibrin-conduit group reached 86% of the control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89% of the controls, respectively. The present results suggest that a tubular fibrin conduit can be used to promote neuronal regeneration following peripheral nerve injury.

Summary Peripheral nerve entrapments of the upper and lower extremity are commonly seen in practice. Chronically repetitive movement patterns lead to constriction of the nerve due to the development of local fibrosis within the soft tissues surrounding the nerve which also affects nerve traction, mobility, and function. A case is presented of a patient with motor weakness in the wrist and hand in order to illustrate the diagnosis and treatment of posterior interosseous nerve (PIN) syndrome. Using Active Release Techniques Soft Tissue Management and Peripheral Nerve Release Systems ® the patient's symptomatology was resolved. Soft tissue-based management in conjunction with neural gliding may be beneficial in the conservative management of PIN syndrome. Further research into the pathophysiology of nerve entrapments will have immediate impact on the management of neuropathies and likely result in emphasizing conservative management and rehabilitation rather than surgical intervention particularly in cases not involving denervation or paralysis.

Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model.

Nerve repair after transection has variable and unpredictable outcomes. In addition to advancements in microvascular surgical techniques, nerve allografts and conduits are available options in peripheral nerve reconstruction. When tensionless nerve repair is not feasible, or in chronic injuries, autografts have been traditionally used. As substitute to autografts, decellularized allografts and conduits have become available. These conduits can reduce donor site morbidity, functional loss at the donor area in cases where autografts are used, and immune reaction from transplants or unprocessed allografts. The development of new biomaterials for use in conduits, as well as use of cytokines, growth factors, and other luminal fillers, may help in the treatment of acute and chronic nerve injuries. The indications and properties of nerve conduits and allografts are detailed in this article.

The treatment of peripheral nerve injuries with nerve gaps largely consists of autologous nerve grafting utilizing sensory nerve donors. Underlying this clinical practice is the assumption that sensory autografts provide a suitable substrate for motoneuron regeneration, thereby facilitating motor endplate reinnervation and functional recovery. This study examined the role of nerve graft modality on axonal regeneration, comparing motor nerve regeneration through motor, sensory, and mixed nerve isografts in the Lewis rat. A total of 100 rats underwent grafting of the motor or sensory branch of the femoral nerve with histomorphometric analysis performed after 5, 6, or 7 weeks. Analysis demonstrated similar nerve regeneration in motor, sensory, and mixed nerve grafts at all three time points. These data indicate that matching of motor-sensory modality in the rat femoral nerve does not confer improved axonal regeneration through nerve isografts.

A novel epineural tube implantation paradigm in the adult rat was designed for the analysis of regulatory cell interactions in peripheral nerves and for the development of therapeutic implants. The aim was to allow the integration of synthetic regenerative structures and cells into the nerve interior while preserving an outer nerve tissue layer with a supportive vasculature. The microsurgical technique allowed us to remove the interfascicular epineurium, leaving behind an epineural tube with an intact tissue wall of about 0.1–0.2 mm. The resulting tube was filled with hundreds of bioengineered bands of Bungner which were composed of resorbable polymer filaments seeded with Schwann cells. Alternatively, purified cells to be analyzed or different types of growth matrices were injected into the epineural tube. Such manipulations will allow to generate and investigate concentration gradients of biological factors or to analyse cell–matrix interactions under defined conditions in a supportive in vivo environment. Our current aim is to evaluate bioengineered neural implants. In summary, a microsurgical in vivo paradigm has been developed to address multiple aspects of peripheral nerve regeneration.

In treating reversible facial paralysis, cross-facial nerve grafting offers voluntary and emotional reanimation. In contrast, rapid re-innervation and strong neural stimulation can be obtained with hypoglossal-facial nerve crossover. In this article, we describe the method of a combination of these techniques as a one-stage procedure. A 39-year-old man presented with facial paralysis due to nerve avulsion within the stylomastoid foramen. The sural nerve was harvested and two branches were created at its distal end by intraneural dissection. One branch was anastomosed to the contralateral facial nerve, and the other branch was used for hypoglossal-facial nerve crossover, followed by connecting the proximal stump of the graft to the trunk of the paralysed facial nerve in an end-to-end fashion. At 9 months postoperatively, almost complete facial symmetry and co-ordinated movements of the mimetic muscles were obtained with no obvious tongue atrophy. Since our method can efficiently gather neural inputs from the contralateral facial nerve and the ipsilateral hypoglossal nerve, it may become a good alternative for reanimation of reversible facial paralysis when the ipsilateral facial nerve is not available.

Summary Background It is well known that free vascularised nerve grafts have a potential for rapid axonal sprouting. However, they are not very popular as the surgical techniques are complicated. With the recent development of supramicrosurgical techniques and microanatomy of nerve trunks, a new method, ‘fascicular turnover method', using vascularised fascicular flap was used for repairing nerve gaps. Methodsand Results Arterial embalming method, using rat sciatic nerves, was employed to observe fascicular micro-vascularisation. Rich vascular network systems were observed within and outside the rat island nerve flaps. Four cases with digital and facial nerves gaps were repaired with fascicular turnover flap without a nerve graft. Three patients had digital nerve gaps (10–20mm in length) and one had a 3-cm facial nerve gap. The results of sensory recovery of digital nerve gap were 3.22–3.66 (Semmes–Weinstein values) and 6–12mm (moving two-point discriminations) at 6 and –16 months after surgery, respectively. Conclusion The advantages of this method are: retention of the normal donor nerve, a shorter operation time and repair of the digital nerve gaps under local anaesthesia. Fascicular flap is a vascularised nerve flap with fast and accurate nerve sprouting in comparison to a non-vascularised graft. Excellent nerve regeneration can be expected even in cases with longer nerve gap and scarred recipient bed. It is a simple and quick surgery compared to free vascularised nerve flaps. In addition, there is no functional loss because of the sacrificed fascicle in the operated area. The only disadvantage is the need to employ superficial palmar branch of radial artery (SPRA)-microsurgical techniques using a 50-micron needle.