Tissue Engineering Strategies Designed to Realize the Endogenous Regenerative Potential of Peripheral Nerves

Mukhatyar, Vivek; Karumbaiah, Lohitash; Yeh, Julie; Bellamkonda, Ravi V.

doi:10.1002/adma.200900746

Cited by 66 publications

(60 citation statements)

References 147 publications

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“…repair, seen in the cellular phase of successful nerve repair [1,7,28,31]. SCs that remain after Wallerian degeneration migrate and proliferate to form aligned glial bands of Bü ngner, during the cellular phase of NGC repair [7,28,29,31].…”

Section: Examples Of Molecular Therapies Include Growth Factors (Vegfmentioning

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.

490

508

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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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Section: Examples Of Molecular Therapies Include Growth Factors (Vegfmentioning

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.

490

508

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“…or at least suffer from drastically reduced muscle strength [1]. Currently, a nerve autograft is the gold standard in treating nerve trunk defects when the tensionless apposition to suture the severed nerve is not possible.…”

mentioning

confidence: 99%

“…Currently, a nerve autograft is the gold standard in treating nerve trunk defects when the tensionless apposition to suture the severed nerve is not possible. Nevertheless, autografts pose various drawbacks, such as the need for a secondary surgery, loss of donor site function, donor site morbidity, limited availability and structural differences between donor and recipient grafts [1,2]. Therefore, there is an urgent and unmet need to find an alternative approach in bridging the nerve defects.…”

mentioning

confidence: 99%

Collagen-Coated Polylactic-Glycolic Acid (PLGA) Seeded with Neural-Differentiated Human Mesenchymal Stem Cells as a Potential Nerve Conduit*

Sulong¹,

Hassan²,

Ng³

et al. 2014

Adv Clin Exp Med

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Background. Autologous nerve grafts to bridge nerve gaps pose various drawbacks. Nerve tissue engineering to promote nerve regeneration using artificial neural conduits has emerged as a promising alternative. Objectives. To develop an artificial nerve conduit using collagen-coated polylactic-glycolic acid (PLGA) and to analyse the survivability and propagating ability of the neuro-differentiated human mesenchymal stem cells in this conduit. Material and Methods. The PLGA conduit was constructed by dip-molding method and coated with collagen by immersing the conduit in collagen bath. The ultra structure of the conduits were examined before they were seeded with neural-differentiated human mesenchymal stem cells (nMSC) and implanted sub-muscularly on nude mice thighs. The non-collagen-coated PLGA conduit seeded with nMSC and non-seeded non-collagen-coated PLGA conduit were also implanted for comparison purposes. The survivability and propagation ability of nMSC was studied by histological and immunohistochemical analysis. Results. The collagen-coated conduits had a smooth inner wall and a highly porous outer wall. Conduits coated with collagen and seeded with nMSCs produced the most number of cells after 3 weeks. The best conduit based on the number of cells contained within it after 3 weeks was the collagen-coated PLGA conduit seeded with neuro-transdifferentiated cells. The collagen-coated PLGA conduit found to be suitable for attachment, survival and proliferation of the nMSC. Minimal cell infiltration was found in the implanted conduits where nearly all of the cells found in the cell seeded conduits are non-mouse origin and have neural cell markers, which exhibit the biocompatibility of the conduits. Conclusions. The collagen-coated PLGA conduit is biocompatible, non-cytotoxic and suitable for use as artificial nerve conduits (Adv Clin Exp Med 2014, 23, 3, 353-362).

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“…These treatments are ineffective as these interventions often lead to painful neuropathies as a result of loss in motor control and sensory perception [1,2]. Over relatively short nerve gaps, spontaneous natural regeneration may occur.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Publication InformationDaly, WT,Yao, L,Abu-rub, MT,O'Connell, C,Zeugolis, DI,Windebank, AJ,Pandit, AS (2012) b s t r a c tThe current microsurgical gold standard for repairing long gap nerve injuries is the autograft. Autograft provides a protective environment for repair and a natural internal architecture, which is essential for regeneration. Current clinically approved hollow nerve guidance conduits allow provision of this protective environment; however they fail to provide an essential internal architecture to the regenerating nerve. In the present study both structured and unstructured intraluminal collagen fibres are investigated to assess their ability to enhance conduit mediated nerve repair. This study presents a direct comparison of both structured and unstructured fibres in vivo. The addition of intraluminal guidance structures was shown to significantly decrease axonal dispersion within the conduit and reduced axonal mismatch of distal nerve targets (p < 0.05). The intraluminal fibres were shown to be successfully incorporated into the host regenerative process, acting as a platform for Schwann cell migration and axonal regeneration. Ultimately the fibres were able to provide a platform for nerve regeneration in a long term regeneration study (16 weeks) and facilitated increased guidance of regenerating axons towards their distal nerve targets.

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Tissue Engineering Strategies Designed to Realize the Endogenous Regenerative Potential of Peripheral Nerves

Cited by 66 publications

References 147 publications

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

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

Collagen-Coated Polylactic-Glycolic Acid (PLGA) Seeded with Neural-Differentiated Human Mesenchymal Stem Cells as a Potential Nerve Conduit*

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

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