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Immunoengineering nerve repair.

ABSTRACT: Injuries to the peripheral nervous system are major sources of disability and often result in painful neuropathies or the impairment of muscle movement and/or normal sensations. For gaps smaller than 10 mm in rodents, nearly normal functional recovery can be achieved; for longer gaps, however, there are challenges that have remained insurmountable. The current clinical gold standard used to bridge long, nonhealing nerve gaps, the autologous nerve graft (autograft), has several drawbacks. Despite best efforts, engineering an alternative "nerve bridge" for peripheral nerve repair remains elusive; hence, there is a compelling need to design new approaches that match or exceed the performance of autografts across critically sized nerve gaps. Here an immunomodulatory approach to stimulating nerve repair in a nerve-guidance scaffold was used to explore the regenerative effect of reparative monocyte recruitment. Early modulation of the immune environment at the injury site via fractalkine delivery resulted in a dramatic increase in regeneration as evident from histological and electrophysiological analyses. This study suggests that biasing the infiltrating inflammatory/immune cellular milieu after injury toward a proregenerative population creates a permissive environment for repair. This approach is a shift from the current modes of clinical and laboratory methods for nerve repair, which potentially opens an alternative paradigm to stimulate endogenous peripheral nerve repair.

SUBMITTER: Mokarram N

PROVIDER: S-EPMC5495274 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Immunoengineering nerve repair.

Mokarram Nassir N Dymanus Kyle K Srinivasan Akhil A Lyon Johnathan G JG Tipton John J Chu Jason J English Arthur W AW Bellamkonda Ravi V RV

Proceedings of the National Academy of Sciences of the United States of America 20170613 26

Injuries to the peripheral nervous system are major sources of disability and often result in painful neuropathies or the impairment of muscle movement and/or normal sensations. For gaps smaller than 10 mm in rodents, nearly normal functional recovery can be achieved; for longer gaps, however, there are challenges that have remained insurmountable. The current clinical gold standard used to bridge long, nonhealing nerve gaps, the autologous nerve graft (autograft), has several drawbacks. Despite ...[more]

PMID: 28611218

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Project description:Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic (phrenic nerve group), intercostal (intercostal nerve group) or thoracodorsal nerves (thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study established an optimized animal model in which suturing the nerve graft to the distal site of the musculocutaneous nerve anastomosis prevented the inhibition of recovery from scar compression.

Project description:BackgroundOver the past five decades, microsuturing has been established as the "gold standard" for nerve repair. Alternative techniques such as fibrin glue, protein "welds", and nerve connectors have been met with variable enthusiasm. While advancements in this area continue, there is little data on surgeon attitude and acceptance of these new techniques.MethodsA short questionnaire was electronically distributed to the members of the American Society for Surgery of the Hand and the American Association of Hand Surgery. Survey questions ascertained demographic information of participants (specialty, years in practice, practice setting, etc.), attitudes about current techniques (what techniques currently used, why, etc.), and attitudes about new techniques (openness to trying, factors that would persuade for/against, etc.). The surveys were distributed and administered online. Data gathered from responses was analyzed looking for general trends and stratified based on demographic data.ResultsThe majority of responders still consider microsuturing as the gold standard for primary nerve repair, and it is by far the most utilized technique. However, over 90 % also reported that they either currently use or would consider using alternate techniques. Common barriers to utilizing alternate techniques included lack of data regarding outcomes and unfamiliarity with new techniques. Only 40 % of responders considered metal as safe around nerves, but most consider absorbable polymers safe. None of the underlying demographic variables including years in practice, number of nerve repair surgeries performed per month, practice setting, or specialty affected these general trends.ConclusionsMost surgeons performing nerve repairs prefer suturing as their primary repair technique, but a vast majority is open to utilizing alternate repair techniques, especially those that improve outcomes with a faster and easier procedure. While not able to direct clinical practice guidelines, this study can be used to direct focus and funding of further alternate nerve repair techniques.

Dataset Information

Immunoengineering nerve repair.

Publications

Immunoengineering nerve repair.

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