Effects of motor versus sensory nerve grafts on peripheral nerve regeneration

Nichols, Chris M.; Brenner, Michael; Fox, Ida K.; Tung, Thomas H.; Hunter, Daniel A.; Rickman, Susan R.; Mackinnon, Susan E.

doi:10.1016/j.expneurol.2004.08.003

Cited by 235 publications

(132 citation statements)

References 40 publications

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“…The study showed that while robust nerve regeneration was observed through motor and mixed nerve grafts, poor nerve regeneration was seen through sensory nerve grafts. These results suggest that motor or mixed nerve grafts might improve clinical outcomes as compared to the current autograft approach that employs a sensory nerve [2]. However, there are few available motor or mixed nerves suitable for use as autografts in the human body.…”

Section: Discussionmentioning

confidence: 79%

“…The clinical "gold standard" for bridging peripheral nerve gaps is the use of autografts (typically, the sensory sural nerve). However, the use of autografts is limited by the following issues: 1) limited availability of nerves to use in the autograft [1], 2) secondary surgery, 3) lack of coaptation between the injured nerve and the nerve graft due to size/length/modality mismatch [2], and 4) functional loss, such as numbness at the donor sites [3]. Moreover, complications at the donor site such as hyperesthesia or formation of painful neuromas also have to be addressed [4,5].…”

Section: Introductionmentioning

confidence: 99%

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The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps

et al. 2008

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Peripheral nerve regeneration across long nerve gaps is clinically challenging. Autografts, the standard of therapy, are limited by availability and other complications. Here, using rigorous anatomical and functional measures, we report that aligned polymer fiber-based constructs present topographical cues that facilitate the regeneration of peripheral nerves across long nerve gaps. Significantly, aligned but not randomly oriented fibers elicit regeneration, establishing that topographical cues can influence endogenous nerve repair mechanisms in the absence of exogenous growth promoting proteins. Axons regenerated across a 17mm nerve gap, reinnervated muscles, and reformed neuromuscular junctions. Electrophysiological and behavioral analyses revealed that aligned, but not randomly oriented constructs facilitated both sensory and motor nerve regeneration, significantly improved functional outcomes. Additionally, a quantitative comparison of DRG outgrowth in vitro and nerve regeneration in vivo on aligned and randomly oriented fiber films clearly demonstrated the significant role of sub-micron scale topographical cues in stimulating endogenous nerve repair mechanisms.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps

et al. 2008

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“…These grafts being taken primarily from the sural nerve of the treated patient and have demonstrated a success rate of only 50 per cent on patients treated [6,10]. These grafts are primarily sensory, owing to the unavailability of motor nerves, limiting their potential to repair pure motor nerve deficits (tibial) and mixed nerve injuries (sciatic) and may be one of the primary reasons for the poor functional recovery rates associated with autografts [11,12]. The use of sensory nerves for the treatment of motor nerve deficits causes morphometric mismatches in the native environments, mismatch in axonal size, distribution and alignment [12,13].…”

Section: Autograft: the Limited Gold Standardmentioning

confidence: 99%

“…These grafts are primarily sensory, owing to the unavailability of motor nerves, limiting their potential to repair pure motor nerve deficits (tibial) and mixed nerve injuries (sciatic) and may be one of the primary reasons for the poor functional recovery rates associated with autografts [11,12]. The use of sensory nerves for the treatment of motor nerve deficits causes morphometric mismatches in the native environments, mismatch in axonal size, distribution and alignment [12,13]. Motor neurons are primarily in the range of 3-20 mm, whereas sensory neurons range from 0.2 to 15 mm [14].…”

Section: Autograft: the Limited Gold Standardmentioning

confidence: 99%

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

Daly

Yao

Zeugolis

et al. 2011

J. R. Soc. Interface.

479

501

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Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative-hollow nerve guidance conduits (NGCs)-have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell-material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic.

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“…Sensory nerve grafts do not promote good motor axon regeneration because sensory and motor nerves express distinct sensory and motor phenotypes that support the regeneration or their specific axon phenotype [35, [91][92][93][94]. Although motor nerve grafts are more effective in promoting axon regeneration across a nerve gap than sensory nerve grafts, they are not used because it is considered unethical to sacrifice a motor nerve function.…”

mentioning

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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Effects of motor versus sensory nerve grafts on peripheral nerve regeneration

Cited by 235 publications

References 40 publications

The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps

The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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