Chitosan tubes enriched with fresh skeletal muscle fibers for delayed repair of peripheral nerve defects

Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.

Emerging issues in peripheral nerve repair

It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that, to further improve clinical outcome, the involvement of different scientific disciplines is required. This evolving reconstructive/regenerative approach is based on the interdisciplinary and integrated pillars of tissue engineering such as reconstructive microsurgery, transplantation and biomaterials. In this paper, some of the most promising innovations for the tissue engineering of nerves, emerging from basic science investigation, are critically overviewed with special focus on those approaches that appear today to be more suitable for clinical translation.

Painful scar neuropathy:principles of diagnosis and treatment

Nerve-tissue interactions are critical.Peripheral nerve injuries may involve intraneural and extraneural scar formation and affect nerve gliding planes,sometimes leading to complex clinical presentations.All of these pathological entities involve pain as the main clinical symptom and can be subsumed under the term“painful scar neuropathy”.The authors review the literature on treatment approaches to peripheral nerve scar neuropathy and the outcomes of neurolysis-associated procedures and propose a simple classification and a therapeutic approach to scar neuropathy.The search retrieved twenty-one papers,twenty of which reported pain reduction or resolution with various techniques.There is no consensus on the best therapeutic approach to neuropathic pain due to scar tethering.Most authors report good or excellent results with different techniques,from nerve wrapping with anti-adhesion devices to nerve coverage or wrapping with vascularized tissue.The authors’classification of and therapeutic approach to peripheral nerve scar lesions aims at promoting a logical approach based on the analysis of lesion type(perineural,or endoneural and perineural),pain type(due to traction or external trauma,pain at rest),and number of previous operations.Patients need to be informed that multiple procedures may be required,that outcomes may be partial,and that surgery can potentially worsen preoperative conditions.The review found no evidence for the best therapeutic approach to scar neuropathy,but there is consensus on a multidisciplinary approach.

Long-term result of guided nerve regeneration with an inert microporous polytetrafluoroethylene conduit

Objective: To evaluate the long term outcome of Polytetrafluoroethylene (PTFE) conduit in nerve repair and to provide more evidence in view of its potential application to achieve a satisfactory functional recovery in clinical settings. Methods: Thirty six Wistar rats had their right sciatic nerve transected and were repaired with either conventional microsuture technique (Control group, n=18) or a PTFE conduit with a gap of 5 mm left between the nerve stumps (PTFE group, n=18). At 6 and 9 months after the operation, electrophysiological assessment and measurement of gastrocnemius muscle weight were conducted and morphology of the regenerated nerves were studied with image analysis. Results: At 6 months postoperatively, the nerve conduction velocity recovered to 60.86 % and 54.36 % (P> 0.05 ), and the gastrocnemius muscle weight recovered to 50.89 % and 46.11 % (P> 0.05 ) in the Control group and the PTFE group respectively. At 9 months postoperatively, the recovery rate was 65.99 % and 58.79 % for NCV (P> 0.05 ), and 52.56 % and 47.89 % for gastrocnemius muscle weight (P> 0.05 ) in the Control group and the PTFE group respectively. Regenerated nerve fibers in the PTFE group had a regular round shape with no fragmentation, wrinkling or splitting of the myelin sheath. Image analysis revealed that the ratio of the myelin area to the total fiber area was larger at 9 months than at 6 months in both groups (P< 0.01 ). Conclusions: Microporous PTFE conduit may be an alternative for nerve repair allowing of guided nerve regeneration and functional recovery with no obvious adverse effect at long term.