Functional restoration of rabbit spinal cord using collagen-filament scaffold

Yoshii, Satoru; Ito, Sadayuki; Shima, Mitsuhiro; Taniguchi, Ataru; Akagi, Masao

doi:10.1002/term.130

Cited by 53 publications

(50 citation statements)

References 39 publications

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“…23,26,28,29,[40][41][42][43] Specifically, aligned collagen constructs were used in neural tissue engineering as nerve guidance conduits. 23,44 Consistent with previous reports of directed neurite elongation along the surface of aligned collagen gels or films, we postulate a similar contact guidance mechanism, and a possible role in specifying neuronal polarity.…”

Section: Directional Neurite Guidance and Polaritysupporting

confidence: 77%

Nano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein

Abu-Rub

Billiar

et al. 2011

Soft Matter

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The UCD community has made this article openly available. Please share how this access benefits you. Your story matters! (@ucd_oa) Some rights reserved. For more information, please see the item record link above. TitleNano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein The development of nerve guidance conduits is constantly evolving as the need arises for therapies for spinal cord injury. In addition to providing a path for regrowing axons to reconnect with their appropriate targets, the structural and biochemical cues provided by these conduits should be permissive for directional neurite outgrowth and be protective against inhibition in the vicinity of the injury site. Here, we adapted the use of iso-electric focusing to drive the alignment of supramolecular fibrils into self-assembled collagen hydrogels ($300 mm diameter), and tested those hydrogels for the ability to direct and enhance the migration of neurites. Structural characterization revealed anisotropic alignment of nanofibrillar aggregates ($20 nm diameter), arranged in micron-scale bundles ($1 to 2 mm diameter) similar to the hierarchical size scales observed in native tissues. Neurite outgrowth extended bidirectionally along the axes of aligned hydrogels. Furthermore, it was shown that, as opposed to poly-D-lysine, neurite outgrowth on aligned hydrogels is not inhibited in the presence of myelin-associated glycoprotein (p > 0.05). These results highlight for the first time a structural and biochemical role for iso-electrically aligned collagen hydrogels in controlling neuronal growth, and indicate that the short-term signaling associated with these hydrogels can be used in adjunct therapy following injury to the spinal cord.

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Section: Directional Neurite Guidance and Polaritysupporting

confidence: 77%

Nano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein

Abu-Rub

Billiar

et al. 2011

Soft Matter

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“…[25][26][27][28][29] A key choice in the development of a tissue-engineered implant is whether to engineer a cellularized construct. [29][30][31][32][33][34][35][36] Cellularized scaffolds may be particularly important when the cells are necessary for maintenance of the surrounding matrix or have an important function, for example, preservation of the antithrombogenicity of a vascular conduit via endothelization or simply to aid continual growth in young recipients. 30,31 Acellular scaffolds have the advantage of delivery as medical devices and avoid the regulatory issues associated with the delivery of living constructs, which require long-term culture in bioreactors.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Regenerative Capacity of an Acellular Porcine Medial Meniscus for Tissue Engineering Applications

Stapleton

Ingram

Fisher

et al. 2011

Tissue Engineering Part A

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Previously, we have described the development of an acellular porcine meniscal scaffold. The aims of this study were to determine the immunocompatibility of the scaffold and capacity for cellular attachment and infiltration to gain insight into its potential for meniscal repair and replacement. Porcine menisci were decellularized by exposing the tissue to freeze-thaw cycles, incubation in hypotonic tris buffer, 0.1% (w/v) sodium dodecyl sulfate in hypotonic buffer plus protease inhibitors, nucleases, hypertonic buffer followed by disinfection using 0.1% (v/v) peracetic, and final washing in phosphate-buffered saline. In vivo immunocompatibility was assessed after implantation of the acellular meniscal scaffold subcutaneously into galactosyltransferase knockout mice for 3 months in comparison to fresh and acellular tissue treated with a-galactosidase (negative control). The cellular infiltrates in the explants were assessed by histology and characterized using monoclonal antibodies against: CD3, CD4, CD34, F4/80, and C3c. Static culture was used to assess the potential of acellular porcine meniscal scaffold to support the attachment and infiltration of primary human dermal fibroblasts and primary porcine meniscal cells in vitro. The explants were surrounded by capsules that were more pronounced for the fresh meniscal tissue compared to the acellular tissues. Cellular infiltrates compromised mononuclear phagocytes, CD34-positive cells, and nonlabeled fibroblastic cells. T-lymphocytes were sparse in all explanted tissue types and there was no evidence of C3c deposition. The analysis revealed an absence of a specific immune response to all of the implanted tissues. Acellular porcine meniscus was shown to be capable of supporting the attachment and infiltration of primary human fibroblasts and primary porcine meniscal cells. In conclusion, acellular porcine meniscal tissue exhibits excellent immunocompatibility and potential for cellular regeneration in the longer term.

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“…The observed directed axonal regeneration from rostral and caudal ends after SCI in the presence of implanted aligned collagen microfilaments supports this notion. 8,9 Compared to microfilaments, nanofibers more closely mimic the size scale and architecture of the natural extracellular matrix and may elicit more physiologically relevant cellular phenotypes. 10,11 Electrospun nanofiber scaffolds, in particular, further permit control over nanofiber alignment to provide contact guidance to seeded cells.…”

mentioning

confidence: 99%

Nanofibrous Collagen Nerve Conduits for Spinal Cord Repair

Liu

Houlé

et al. 2012

Tissue Engineering Part A

132

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Nerve regeneration in an injured spinal cord is often restricted, contributing to the devastating outcome of neurologic impairment below the site of injury. Although implantation of tissue-engineered scaffolds has evolved as a potential treatment method, the outcomes remain sub-optimal. One possible reason may be the lack of topographical signals from these constructs to provide contact guidance to invading cells or regrowing axons. Nanofibers mimic the natural extracellular matrix architecturally and may therefore promote physiologically relevant cellular phenotypes. In this study, the potential application of electrospun collagen nanofibers (diameter = 208.2 -90.4 nm) for spinal cord injury (SCI) treatment was evaluated in vitro and in vivo. Primary rat astrocytes and dorsal root ganglias (DRGs) were seeded on collagen-coated glass cover slips (two-dimensional [2D] substrate controls), and randomly oriented or aligned collagen fibers to evaluate scaffold topographical effects on astrocyte behavior and neurite outgrowth, respectively. When cultured on collagen nanofibers, astrocyte proliferation and expression of glial fibrillary acidic protein (GFAP) were suppressed as compared to cells on 2D controls at days 3 ( p < 0.05) and 7 ( p < 0.01). Aligned fibers resulted in elongated astrocytes (elongation factor > 4, p < 0.01) and directed the orientation of neurite outgrowth from DRGs along fiber axes. In the contrast, neurites emanated radially on randomly oriented collagen fibers. By forming collagen scaffolds into spiral tubular structures, we demonstrated the feasibility of using electrospun nanofibers for the treatment of acute SCI using a rat hemi-section model. At days 10 and 30 postimplantation, extensive cellular penetration into the constructs was observed regardless of fiber orientation. However, scaffolds with aligned fibers appeared more structurally intact at day 30. ED1 immunofluorescent staining revealed macrophage invasion by day 10, which decreased significantly by day 30. Neural fiber sprouting as evaluated by neurofilament staining was observed as early as day 10. In addition, GFAP immunostained astrocytes were found only at the boundary of the lesion site, and no astrocyte accumulation was observed in the implantation area at any time point. These findings indicate the feasibility of fabricating 3D spiral constructs using electrospun collagen fibers and demonstrated the potential of these scaffolds for SCI repair.

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Functional restoration of rabbit spinal cord using collagen-filament scaffold

Cited by 53 publications

References 39 publications

Nano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein

Nano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein

Investigation of the Regenerative Capacity of an Acellular Porcine Medial Meniscus for Tissue Engineering Applications

Nanofibrous Collagen Nerve Conduits for Spinal Cord Repair

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