Peripheral Nerve Injury and Repair

Lee, Steve K.; Wolfe, Scott W.

doi:10.5435/00124635-200007000-00005

Cited by 546 publications

(386 citation statements)

References 30 publications

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“…Only ~40-50% of patients regain useful function when treated with autografts, the current clinical gold standard [23]. These imperfect results might be explained by a recent study that examined the effects of motor versus sensory nerve grafts on peripheral nerve regeneration.…”

Section: Discussionmentioning

confidence: 91%

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: 91%

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

et al. 2008

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“…Moreover, there is a frequent size mismatch of donor nerves and a low success rate of only 50%, with higher rates of failure for patients above 50 years and for defects longer than 7 cm (Lee and Wolfe, 2000). For the past two decades, several biomaterials have been developed to facilitate accelerated repair and better axon regeneration (Belkas et al, 2004;Biazar et al, 2010;Chang et al, 2007;Daly et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Decellularized grafts with axially aligned channels for peripheral nerve regeneration

Sridharan

Reilly

Buckley

2015

Journal of the Mechanical Behavior of Biomedical Materials

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At least 2 million people worldwide suffer annually from peripheral nerve injuries (PNI), with estimated costs of $7 billion incurred due to paralysis alone. The current "gold" standard for treatment of PNI is the autograft, which poses disadvantages such as high fiscal cost, possible loss of sensation at donor site and the requirement of two surgeries. Allografts are viable alternatives; however, intensive immunosuppressive treatments are often necessary to prevent host rejection. For this reason, significant efforts have been made to remove cellular material from allografts. These decellularized nerve grafts perform better than other clinically available grafts but not as well as autografts; therefore, current research on these grafts includes the incorporation of additional components such as growth factors and cells to provide chemical guidance to regenerating axons. However, effective cellular and axonal penetration is not achieved due to the small pore size (5-10μm) of the decellularized grafts.The overall objective of this study was to induce axially aligned channels in decellularized nerve grafts to facilitate enhanced cell penetration. The specific aims of this study were to optimize a decellularization method to enhance cellular removal, to induce axially aligned pore formation in decellularized grafts through a novel unidirectional freeze drying method, to study the bulk mechanical properties of these modified decellularized grafts and to assess cell penetration into these grafts. To this end we modified an existing decellularization protocol to improve cellular removal while preserving matrix structure in rat sciatic nerve sections. Standard freeze drying and unidirectional freeze drying were employed to impart the necessary pore architecture, and our results suggest that unidirectional freezing is a pertinent modification to the freeze drying process to obtain axially aligned channels. These highly porous scaffolds obtained using unidirectional freeze-drying possessed similar tensile properties to native nerve tissue and exhibited enhanced cellular penetration after 14 days of culture when compared to non-freeze dried and standard freeze-dried scaffolds. The results of this study not only highlight the importance of aligned pores of diameters ~20-60μm on cellular infiltration, but also presents unidirectional freeze drying as a viable technique for producing this required architecture in decellularized nerves. To the best of our knowledge, this study represents the first attempt to manipulate the physical structure of decellularized nerves to enhance cell penetration which may serve as a basis for future peripheral nerve regenerative strategies using decellularized allografts.

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“…Muscle fibrosis and atrophy phenomena begin immediately after denervation and are called neurogenic atrophy. After 4 months, a plateau is reached, when 60-80% of muscle mass is lost, and although motor end plates increase, beyond a 12-month period, a functional muscle re-enervation is highly unlikely [30,39,62]. The time frame for sensory re-enervation is longer but not endless, and early repair also grants better results [30,39].…”

Section: Timing Of Medical Interventionmentioning

confidence: 99%

“…The SCs form organized longitudinal structures inside the endoneurium-called bands of Büngner [30,34]-that are critical to the axonal regeneration. At the distal site of lesion, the node of Ranvier, around 50-100 finger-like sprouts, starts to form a growth cone directed to the distal nerve stump [39]. Proteases are also released from the growth cone by the influence of several factors, clearing the way towards the target tissue.…”

Section: Nerve Response To Injurymentioning

confidence: 99%

“…After 4 months, a plateau is reached, when 60-80% of muscle mass is lost, and although motor end plates increase, beyond a 12-month period, a functional muscle re-enervation is highly unlikely [30,39,62]. The time frame for sensory re-enervation is longer but not endless, and early repair also grants better results [30,39]. In Figure 2, we present the peripheral nerve injuries repair algorithm which helps to understand the variables taken into account in the selection of best nerve repair strategy.…”

Section: Timing Of Medical Interventionmentioning

confidence: 99%

See 1 more Smart Citation

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Pedrosa¹,

Caseiro²,

Santos³

et al. 2017

Scaffolds in Tissue Engineering - Materials, Technologies and Clinical Applications

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Human adult peripheral nerve injuries are a high incidence clinical problem that greatly affects patients' quality of life. Although peripheral nervous system has intrinsic regenerative capacity, this occurs in an incomplete or poorly functional manner. When a nerve fiber loses its continuity with consequent damage of the basal lamina tubes, axon spontaneous regeneration is disorganized and mismatched. These phenomena translate in an inadequate nerve functional recovery and consequent musculoskeletal incapacity. Nerve grafts still remain the gold standard in peripheral injuries treatment. However, this approach contains its disadvantages such as the necessity of primary surgery to harvest the autografts, loss of a functional nerve, donor site morbidity and longer surgery procedures. Therefore, biomaterials and tissue engineering can provide efficient resources and alternatives to nerve injury repair not only by the development of biocompatible structures but also, introducing neurotrophic factors and cellular systems to stimulate optimum clinical outcome. In this chapter, a comprehensive state-of-the art picture of tissue-engineered nerve grafts scaffolds, their application in nerve regeneration along with latest advances in peripheral nerve repair and future perspectives will be discussed, including our own large experience in this field of knowledge.

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Peripheral Nerve Injury and Repair

Cited by 546 publications

References 30 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

Decellularized grafts with axially aligned channels for peripheral nerve regeneration

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

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