Strategies for Peripheral Nerve Repair

Wilcox, Matthew; Gregory, Holly; Powell, Rebecca; Quick, Tom; Phillips, James B.

doi:10.1007/s43152-020-00002-z

Cited by 21 publications

(16 citation statements)

References 123 publications

(142 reference statements)

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“…Despite significant progress in the treatment of injuries of bone, blood vessels, and soft tissues, relatively little clinical progress has been made in the treatment of major PNIs. Despite decades of research with growth factors, cell cultures, engineered conduits, etc., the gold standard for repair of major PNI is a primary repair (for a simple transection injury) or autograft nerve reconstruction (for segmental or “ablation” type injuries), with microsurgical technique just as it has been for the last 30 or more years [ 167 – 170 ]. The commercialization of conduits and acellular nerve allografts has been a helpful adjunct.…”

Section: Discussionmentioning

confidence: 99%

“…The commercialization of conduits and acellular nerve allografts has been a helpful adjunct. However, the gold standard of cable autograft neurorrhaphy still persists and functional recovery from major segmental-loss PNIs still remains a slow and incomplete process for most adult patients and experimental animals [ 1 – 7 , 64 , 66 , 167 – 170 ].…”

Section: Discussionmentioning

confidence: 99%

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Typical and atypical properties of peripheral nerve allografts enable novel strategies to repair segmental-loss injuries

Bittner

Bushman

Ghergherehchi

et al. 2022

J Neuroinflammation

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We review data showing that peripheral nerve injuries (PNIs) that involve the loss of a nerve segment are the most common type of traumatic injury to nervous systems. Segmental-loss PNIs have a poor prognosis compared to other injuries, especially when one or more mixed motor/sensory nerves are involved and are typically the major source of disability associated with extremities that have sustained other injuries. Relatively little progress has been made, since the treatment of segmental loss PNIs with cable autografts that are currently the gold standard for repair has slow and incomplete (often non-existent) functional recovery. Viable peripheral nerve allografts (PNAs) to repair segmental-loss PNIs have not been experimentally or clinically useful due to their immunological rejection, Wallerian degeneration (WD) of anucleate donor graft and distal host axons, and slow regeneration of host axons, leading to delayed re-innervation and producing atrophy or degeneration of distal target tissues. However, two significant advances have recently been made using viable PNAs to repair segmental-loss PNIs: (1) hydrogel release of Treg cells that reduce the immunological response and (2) PEG-fusion of donor PNAs that reduce the immune response, reduce and/or suppress much WD, immediately restore axonal conduction across the donor graft and re-innervate many target tissues, and restore much voluntary behavioral functions within weeks, sometimes to levels approaching that of uninjured nerves. We review the rather sparse cellular/biochemical data for rejection of conventional PNAs and their acceptance following Treg hydrogel and PEG-fusion of PNAs, as well as cellular and systemic data for their acceptance and remarkable behavioral recovery in the absence of tissue matching or immune suppression. We also review typical and atypical characteristics of PNAs compared with other types of tissue or organ allografts, problems and potential solutions for PNA use and storage, clinical implications and commercial availability of PNAs, and future possibilities for PNAs to repair segmental-loss PNIs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Typical and atypical properties of peripheral nerve allografts enable novel strategies to repair segmental-loss injuries

Bittner

Bushman

Ghergherehchi

et al. 2022

J Neuroinflammation

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“…Both embryonic and adult stem cell sources have been reviewed elsewhere [ 42 , 43 , 44 , 45 , 46 ] and various SCs differentiation protocols have been developed with some success. For example, SCs differentiated from embryonic stem cells (ESCs) express SC markers and associate with axons in vitro, suggesting myelination ability [ 47 ].…”

Section: Alternative Sources Of Schwann Cellsmentioning

confidence: 99%

Perspective on Schwann Cells Derived from Induced Pluripotent Stem Cells in Peripheral Nerve Tissue Engineering

Huang

Powell

Phillips

et al. 2020

Cells

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Schwann cells play a crucial role in successful peripheral nerve repair and regeneration by supporting both axonal growth and myelination. Schwann cells are therefore a feasible option for cell therapy treatment of peripheral nerve injury. However, sourcing human Schwann cells at quantities required for development beyond research is challenging. Due to their availability, rapid in vitro expansion, survival, and integration within the host tissue, stem cells have attracted considerable attention as candidate cell therapies. Among them, induced pluripotent stem cells (iPSCs) with the associated prospects for personalized treatment are a promising therapy to take the leap from bench to bedside. In this critical review, we firstly focus on the current knowledge of the Schwann cell phenotype in regard to peripheral nerve injury, including crosstalk with the immune system during peripheral nerve regeneration. Then, we review iPSC to Schwann cell derivation protocols and the results from recent in vitro and in vivo studies. We finally conclude with some prospects for the use of iPSCs in clinical settings.

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“…Although it is flexible, it is not compressible, i.e., its lumen does not collapse. Such construction is highly desired by surgeons, who can easily put them on resected nerve stamps during surgery [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

Fabrication and Characterization of Polycaprolactone/Chitosan—Hydroxyapatite Hybrid Implants for Peripheral Nerve Regeneration

2021

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Major efforts for the advancement of tubular-shaped implant fabrication focused recently on the development of 3D printing methods that can enable the fabrication of complete devices in a single printing process. However, the main limitation of these solutions is the use of non-biocompatible polymers. Therefore, a new technology for obtaining hybrid implants that employ polymer extrusion and electrophoretic deposition is applied. The fabricated structures are made of two layers: polycaprolactone skeleton and chitosan–hydroxyapatite electrodeposit. Both of them can be functionalized by incorporation of mechanical or biological cues that favor ingrowth, guidance, and correct targeting of axons. The electrodeposition process is conducted at different voltages in order to determine the influence of this process on the structural, chemical, and mechanical properties of implants. In addition, changes in mechanical properties of implants during their incubation in phosphate-buffered solution (pH 7.4) at 37 °C up to 28 days are examined. The presented technology, being low-cost and relatively simple, shall find a broad scope of applications in customized nerve tissue engineering.

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Strategies for Peripheral Nerve Repair

Cited by 21 publications

References 123 publications

Typical and atypical properties of peripheral nerve allografts enable novel strategies to repair segmental-loss injuries

Typical and atypical properties of peripheral nerve allografts enable novel strategies to repair segmental-loss injuries

Perspective on Schwann Cells Derived from Induced Pluripotent Stem Cells in Peripheral Nerve Tissue Engineering

Fabrication and Characterization of Polycaprolactone/Chitosan—Hydroxyapatite Hybrid Implants for Peripheral Nerve Regeneration

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