Multiple-channel scaffolds to promote spinal cord axon regeneration

Moore, Michael J.; Friedman, Jonathan A.; Lewellyn, Eric B.; Mantila, Sara M.; Krych, Aaron J.; Ameenuddin, Syed; Knight, Andrew M.; Lu, Lichun; Currier, Bradford L.; Spinner, Robert J.; Marsh, Roger R.; Windebank, Anthony J.; Yaszemski, Michael J.

doi:10.1016/j.biomaterials.2005.07.045

Cited by 259 publications

(210 citation statements)

References 37 publications

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“…A number of studies aiming at the repair of nerve or brain tissue have been conducted with promising results, especially those which used cylindrical or tubular structures to mimic nervous tracts [9][10][11]. These anisotropic structures provide physical guidance for cell migration and axonal penetration and elongation and they permit the investigation of the effects of guidance stimuli to achieve efficient functional regeneration.…”

Section: Introductionmentioning

confidence: 99%

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

et al. 2016

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Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-L-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10 days.The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel's surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5 mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell-material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system.

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Section: Introductionmentioning

confidence: 99%

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

et al. 2016

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“…An 85:15 polylactic acid:polyglycolic acid (PLGA) scaffold maintains its structural integrity for at least 8 weeks and starts to degrade significantly by 24 weeks. 5 Polylactic acid and polyglycolic acid polymers and their copolymers have been used extensively in clinical practice and have been found to be biocompatible. [6][7][8] Two clinical studies used PLGA guidance channels for peripheral nerve regeneration without significant adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Neural Stem Cell– and Schwann Cell–Loaded Biodegradable Polymer Scaffolds Support Axonal Regeneration in the Transected Spinal Cord

Olson

Rooney

Gross

et al. 2009

Tissue Engineering Part A

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Biodegradable polymer scaffolds provide an excellent approach to quantifying critical factors necessary for restoration of function after a transection spinal cord injury. Neural stem cells (NSCs) and Schwann cells (SCs) support axonal regeneration. This study examines the compatibility of NSCs and SCs with the poly-lacticco-glycolic acid polymer scaffold and quantitatively assesses their potential to promote regeneration after a spinal cord transection injury in rats. NSCs were cultured as neurospheres and characterized by immunostaining for nestin (NSCs), glial fibrillary acidic protein (GFAP) (astrocytes), bIII-tubulin (immature neurons), oligodendrocyte-4 (immature oligodendrocytes), and myelin oligodendrocyte (mature oligodendrocytes), while SCs were characterized by immunostaining for S-100. Rats with transection injuries received scaffold implants containing NSCs (n ¼ 17), SCs (n ¼ 17), and no cells (control) (n ¼ 8). The degree of axonal regeneration was determined by counting neurofilament-stained axons through the scaffold channels 1 month after transplantation. Serial sectioning through the scaffold channels in NSC-and SC-treated groups revealed the presence of nestin, neurofilament, S-100, and bIII tubulin-positive cells. GFAP-positive cells were only seen at the spinal cord-scaffold border. There were significantly more axons in the NSC-and SC-treated groups compared to the control group. In conclusion, biodegradable scaffolds with aligned columns seeded with NSCs or SCs facilitate regeneration across the transected spinal cord. Further, these multichannel biodegradable polymer scaffolds effectively serve as platforms for quantitative analysis of axonal regeneration.

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“…4C). Multichannel conduits that had already been developed for other purposes (increased surface area for Schwann cell attachment 29 and experimental spinal cord repair 46 ) were used to investigate this. In a pilot study with multichannel poly(lacticcoglycolic acid) nerve tubes the percentage of double projections was indeed slightly decreased, although not significantly (16.9% 8 weeks after multichannel nerve tube repair and 21.4% 8 weeks after single-lumen nerve tube).…”

Section: Physical Guidance Of Nerve Regeneration With Modified Conduitsmentioning

confidence: 99%

Misdirection and guidance of regenerating axons after experimental nerve injury and repair

Ruiter

Spinner

Verhaagen

et al. 2014

JNS

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Misdirection of regenerating axons is one of the factors that can explain the limited results often found after nerve injury and repair. In the repair of mixed nerves innervating different distal targets (skin and muscle), misdirection may, for example, lead to motor axons projecting toward skin, and vice versa-that is, sensory axons projecting toward muscle. In the repair of motor nerves innervating different distal targets, misdirection may result in reinnervation of the wrong target muscle, which might function antagonistically. In sensory nerve repair, misdirection might give an increased perceptual territory. After median nerve repair, for example, this might lead to a dysfunctional hand.Different factors may be involved in the misdirection of regenerating axons, and there may be various mechanisms that can later correct for misdirection. In this review the authors discuss these different factors and mechanisms that act along the pathway of the regenerating axon. The authors review recently developed evaluation methods that can be used to investigate the accuracy of regeneration after nerve injury and repair (including the use of transgenic fluorescent mice, retrograde tracing techniques, and motion analysis). In addition, the authors discuss new strategies that can improve in vivo guidance of regenerating axons (including physical guidance with multichannel nerve tubes and biological guidance accomplished using gene therapy). 493Abbreviations used in this paper: BDNF = brain-derived neurotrophic factor; DY = diamidino yellow; FB = fast blue; GC = growth cone; GDNF = glial cell line-derived neurotrophic factor; LV = lentiviral vector; NGF = nerve growth factor.

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Multiple-channel scaffolds to promote spinal cord axon regeneration

Cited by 259 publications

References 37 publications

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

Neural Stem Cell– and Schwann Cell–Loaded Biodegradable Polymer Scaffolds Support Axonal Regeneration in the Transected Spinal Cord

Misdirection and guidance of regenerating axons after experimental nerve injury and repair

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