Peripheral nerve regeneration through alginate gel: analysis of early outgrowth and late increase in diameter of regenerating axons

Hashimoto, Tadashi; Suzuki, Yoshihisa; Kitada, Masaaki; Kataoka, K.; Wu, Sufan; Suzuki, Kyoko; Endo, Kaori; Nishimura, Yoshihiko; Idé, Chizuka

doi:10.1007/s00221-002-1173-y

Cited by 106 publications

(84 citation statements)

References 43 publications

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“…pancreatic islets, recombinant cells) and has been fabricated in various forms for regeneration of neural tissue, including tubes [8], freeze-dried sponges [10,11] and hydrogels [12,13]. Hashimoto et al [11] studied peripheral nerve regeneration through freeze-dried, covalently crosslinked alginate gel placed in 10mm defects in the rat sciatic nerve. Axons extended approximately 100µm into the material 4 days post-implantation, while SCs migrated into the gel at the distal lesion site over 8-14 days.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair

Lin

Wang

Wertheim

et al. 2017

Materials Science and Engineering: C

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The prospects for successful peripheral nerve repair using fibre guides are considered to be enhanced by the use of a scaffold material, which promotes attachment and proliferation of glial cells and axonal regeneration. Macroporous alginate fibers were produced by extraction of gelatin particle porogens from wet spun fibers produced using a suspension of gelatin particles in 1.5% w/v alginate solution. Gelatin loading of the starting suspension of 40.0, 57.0, and 62.5% w/w resulted in gelatin loading of the dried alginate fibers of 16, 21, and 24% w/w respectively. Between 45 and 60% of the gelatin content of hydrated fibers was released in 1 h in distilled water at 37°C, leading to rapid formation of a macroporous structure. Confocal laser scanning microscopy (CLSM) and image processing provided qualitative and quantitative analysis of mean equivalent macropore diameter (48-69 µm), pore size distribution, estimates of maximum porosity (14.6%) and pore connectivity.CLSM also revealed that gelatin residues lined the macropore cavities and infiltrated into the body of the alginate scaffolds, thus, providing cell adhesion molecules, which are potentially advantageous for promoting growth of glial cells and axonal extension. Macroporous alginate fibres encapsulating nerve cells [primary rat dorsal root ganglia (DRGs)] were produced by wet spinning alginate solution containing dispersed gelatin particles and DRGs. Marked outgrowth was evident over a distance of 150 µm at day 11 in cell culture, indicating that pores and channels created within the alginate hydrogel were providing a favourable environment for neurite development. These findings indicate that macroporous alginate fibres encapsulating nerve cells may provide the basis of a useful strategy for nerve repair.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair

Lin

Wang

Wertheim

et al. 2017

Materials Science and Engineering: C

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“…46 In another study, it was concluded that alginate gel presents a good biocompatibility for regenerating axon outgrowth and Schwann cell migration, which leads to the conclusion that alginate gel is a promising material for use as an implant for peripheral nerve regeneration. 47 …”

Section: Alginatementioning

confidence: 99%

Regeneration of the peripheral nerve — Development and evaluation of guide tubes of biodegradable polymer

Gomes

Santos

Maurício

2017

2017 IEEE 5th Portuguese Meeting on Bioengineering (ENBENG)

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ii © Joana Gomes, 2014 iii iv ResumoDanos nas fibras nervosas periféricas resultam em perda axonal e desmielinização, seguidos de regeneração e remielinização sob condições ideais com a possibilidade de alguma recuperação funcional. Estudos recentes indicam que a diferença na regeneração axonal entre o sistema nervoso periférico (PNS) e o sistema nervoso central (CNS) resulta da presença de fatores permissivos presentes no PNS e fatores inibitórios ativos presentes no CNS.Pacientes com lesões no nervo periférico estão muitas vezes no auge da sua atividade laboral, o que faz da regeneração do nervo periférico um foco principal de pesquisa. Assim, o desafio experimental consiste em acelerar a regeneração axonal para promover a reinervação e melhorar a recuperação funcional após uma lesão no nervo periférico. Algumas das abordagens experimentais para melhorar a recuperação funcional incluem a aplicação focal de fatores neurotróficos, o bloqueio de moléculas inibidoras da regeneração axonal e o transplante de células.Depois de ocorrer uma lesão quer de axonotmese quer de neurotmese, os axónios periféricos têm a capacidade de se regenerar e de se ligar novamente aos seus alvos, sendo que no primeiro caso não há necessidade de reconstrução cirúrgica uma vez que o endoneuro, perineuro e epineuro são mantidos. No entanto, o estado funcional resultante pode não ser o melhor uma vez que a regeneração é demorada e conduz à atrofia neurogénica dos músculos regionais. Na prática clínica, a reparação cirúrgica ideal em situações de neurotmese (seccionamento total do nervo) considera-se ser a sutura topo-a-topo, de modo a aproximar o topo distal do topo proximal, sem haver tensão no local da sutura. Alternativamente, nervos autólogos são o gold standard deste tipo de procedimentos sempre que ocorre perda de substância e não seja possível executar uma sutura topo-a-topo sem tensão. No entanto, o uso de autoenxertos está limitado pelos inconvenientes inerentes uma vez que requer uma segunda cirurgia, com sacrifício de um nervo funcional, o que resulta em perda sensorial e morbidade do local de doação, entre outros.Nas últimas décadas, os diferentes tipos de enxertos artificiais ou biológicos foram desenvolvidos e investigados para que pudesse ser estabelecida uma relação entre eles e os enxertos de nervos autólogos em termos dos resultados da regeneração do nervo e da v recuperação funcional. Estes tubos-guia são projetados para preencher a lacuna existente num nervo seccionado quando existe um gap, para limitar a fibrose e orientar as fibras em regeneração na direção do topo distal. O enxerto de nervo artificial é um canal tubular feito de materiais sintéticos ou biodegradáveis e que pode orientar a regeneração do axónio sem inibir o crescimento e maturação. O canal tubular pode ser implantado vazio ou preenchido com fatores de crescimento, células ou fibras. Devido à sua capacidade de renovação, multiplicação e diferenciação, as células estaminais mesenquimatosas (MSCs) têm sido usadas para suplementar os tubos-guia, sendo ...

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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].…”

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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Peripheral nerve regeneration through alginate gel: analysis of early outgrowth and late increase in diameter of regenerating axons

Cited by 106 publications

References 43 publications

Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair

Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair

Regeneration of the peripheral nerve — Development and evaluation of guide tubes of biodegradable polymer

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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