The effect of intraluminal contact mediated guidance signals on axonal mismatch during peripheral nerve repair

Daly, William T.; Yao, Li; Abu-Rub, Mohammad; O’Connell, Claire; Zeugolis, Dimitrios I.; Windebank, Anthony J.; Pandit, Abhay

doi:10.1016/j.biomaterials.2012.06.002

Cited by 67 publications

(59 citation statements)

References 40 publications

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“…More advanced therapies are also well documented where the conduit is used to deliver growth factors (e.g. neurotrophin-3/neurotrophin-4 [33]), cytoprotective agents [34], the inclusion of internal guidance structures (as channels [19,35] or fibres [31,36e38]) and where the conduit is used in combination with a cell therapy, including the local delivery of support cells for stimulating proximal axon regeneration (e.g. Schwann cells [39,40]) or adult-derived stem cells, both as bone marrow-derived mesenchymal [41] or adipose-derived cells [42e45]).…”

Section: Discussionmentioning

confidence: 99%

Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair

et al. 2015

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The peripheral nervous system has a limited innate capacity for self-repair following injury, and surgical intervention is often required. For injuries greater than a few millimeters autografting is standard practice although it is associated with donor site morbidity and is limited in its availability. Because of this, nerve guidance conduits (NGCs) can be viewed as an advantageous alternative, but currently have limited efficacy for short and large injury gaps in comparison to autograft. Current commercially available NGC designs rely on existing regulatory approved materials and traditional production methods, limiting improvement of their design. The aim of this study was to establish a novel method for NGC manufacture using a custom built laser-based microstereolithography (μSL) setup that incorporated a 405 nm laser source to produce 3D constructs with ∼ 50 μm resolution from a photocurable poly(ethylene glycol) resin. These were evaluated by SEM, in vitro neuronal, Schwann and dorsal root ganglion culture and in vivo using a thy-1-YFP-H mouse common fibular nerve injury model. NGCs with dimensions of 1 mm internal diameter × 5 mm length with a wall thickness of 250 μm were fabricated and capable of supporting re-innervation across a 3 mm injury gap after 21 days, with results close to that of an autograft control. The study provides a technology platform for the rapid microfabrication of biocompatible materials, a novel method for in vivo evaluation, and a benchmark for future development in more advanced NGC designs, biodegradable and larger device sizes, and longer-term implantation studies.

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Section: Discussionmentioning

confidence: 99%

Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair

et al. 2015

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“…Further in vitro analysis demonstrated that such materials, largely attributed to their surface features, not only facilitate bidirectional cell alignment, but also maintain tenogenic phenotype in vitro [360]. Further, preclinical experimentation in peripheral nerve repair and in tendon small and large animal models enhanced the clinical potential of these fibres, as judged by improved structural alignment and biomechanics [361][362][363]. Using an isoelectric focusing setup, aligned collagen fibres have been produced with ultrastructural characteristics and physical properties similar to native tendon [364,365].…”

Section: Bottom-up Approached For Tendon Repair Based On Natural In Omentioning

confidence: 99%

The past, present and future in scaffold-based tendon treatments

Lomas

Ryan

Sorushanova

et al. 2015

Advanced Drug Delivery Reviews

183

188

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“…Among 165], collagen gel tubes [166], bioartificial nerve graft seeded with Schwann cells [167], Schwann cells modified to over-express specific growth factors [168][169][170], conduits of synthetic materials [147,153,171,172], the infusion of antibodies [173], gradients of factors within tubes [174], allographs [175], factors that induce inflammation [149,176], pseudo nerves [177], alginate gel [178], biodegradable polymer tubes [179], tubes filled with platelet-rich plasma [180][181][182], and arteries, veins and muscle tubes [160, 183,184]. None of these techniques induces more effective axon regeneration than autologous sensory nerve grafts [20,31,[185][186][187][188]. Therefore, despite their significant limitation in inducing axon regeneration, sensory nerve grafts remain the "gold standard" for clinical peripheral nerve repair [3,99,110,106,148,[189][190][191][192][193].…”

Section: Alternative Tested Techniques For Bridging Nerve Gapsmentioning

confidence: 99%

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

Kuffler¹

2015

Int J Neurorehabilitation Eng

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Repairing Peripheral Nerves following Traumas Nerve crushWithin several days of crushing a peripheral nerve, the injured axons begin to regenerate through their distal pathway until they reach their original targets with which they restore neurological function. The larger the number of axons that regenerate through the distal nerve, the greater the extent of neurological recovery [1][2][3]. The number of axons that regenerate, and thus neurological recovery, is influenced by the physiological state of the distal denervated nerve pathway [4][5][6][7].Following a peripheral nerve crush, the injured axons begin to regenerate within 2 days of injury [8]. They may regenerate to their targets through their original pathway in association with and promoted by its Schwann cells, the neurotrophic factors they release, and the Schwann cell extracellular matrix [1,4,[9][10][11][12][13][14]. Thus, the distal nerve provides a simple means for promoting and directing the regenerating axons to their original targets [15][16][17][18]. However, when a nerve has a gap, the gap must be bridged with a material that is permissive to and promotes axon regeneration across the entire gap to reach the distal nerve stump, through which the axons must then be able to regenerate.The Schwann cells in the denervated distal nerve release neurotrophic factors that promote axon regeneration, but also release extracellular matrix components that promote and inhibit axon regeneration [19][20][21][22][23][24][25][26]. Thus, regeneration through the distal nerve is a balance of the influences of factors that both promote and inhibit regeneration. If the Schwann cells are present, such as after a simple nerve crush, virtually 100% of the axons regenerate and they innervate all the denervated synaptic sites. If the Schwann cells within the distal nerve pathway are killed, leaving only the extracellular matrix intact, the number of axons that regenerates to their targets decreases by 94%. This is because the factors required to trigger the regenerating axons to branch at extracellular matrix branch points are missing, axons do not branch, and therefore each axon reinnervates only a single denervated muscle fiber. Thus, Schwann cells along the distal nerve pathway and a AbstractFollowing a peripheral nerve crush, or when a peripheral the nerve is transected and the nerve stumps anastomosed, neurological recovery is generally excellent. This is because the axons merely have to regenerate through the distal portion of the nerve through the existing extracellular matrix of the denervated Schwann cells that direct and promote them to their distant denervated motor and sensory targets. However, when a length of a peripheral nerve is destroyed, and anastomosis is not possible, the standard surgical repair technique is to graft a length/s of autologous sensory nerve into the gap. Neurological recovery is generally good if the nerve gap is <2 cm in length, the repair is performed <4 months post trauma, and the patients are <25 years of age. Because the nerve ...

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The effect of intraluminal contact mediated guidance signals on axonal mismatch during peripheral nerve repair

Cited by 67 publications

References 40 publications

Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair

Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair

The past, present and future in scaffold-based tendon treatments

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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