The fabrication and characterization of linearly oriented nerve guidance scaffolds for spinal cord injury

Stokols, Shula; Tuszynski, Mark H.

doi:10.1016/j.biomaterials.2004.01.041

Cited by 217 publications

(152 citation statements)

References 18 publications

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“…The biocompatibility of PHEMA has been recognized as a potential problem in CNS repair studies. Benefits improves neuronal survival [96] Potentially increases axonal growth [97] Biocompatible; thermal gelling; improves neurite extension [104,105] ; flexible and stable in culture conditions [106] Enhances cell resistance to oxidative stress [108] ; increases neuronal regeneration [108] ; negatively charged [109] ; biocompatible; biodegradable Directs stem cells to a neuronal lineage [111] Promotes axon regeneration across injury site [113] FDA-approved for use in brain, non-toxic, thermally sensitive, functionalizable…”

Section: Synthetic Polymersmentioning

confidence: 99%

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Biomaterials for spinal cord repair

Haggerty

Oudega

2013

Neurosci. Bull.

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Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCi. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCi. A plethora of biomaterials is available and has been tested in various models of SCi. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi.Keywords: spinal cord injury; axon regeneration; biodegradable materials; extracellular matrix proteins; functional recovery; growth factor; guidance; injury and repair; spinal motor neuron IntroductionSpinal cord injury (SCi) causes loss of neurons and axons resulting in motor and sensory function impairments. There are thousands of new cases of SCi in the world annually [1,2] occurring often in young adults. The lack of endogenous repair and the significant costs to the individual, family and society [1] are important motivations behind the continuing efforts to develop effective therapies. Promoting axonal regeneration is considered a potential repair strategy because it could lead to recovery of axonal circuits involved in motor and/or sensory function [3] .The central nervous system (CNS) neurons are intrinsically capable of some regeneration of damaged axons [4] but their attempts after SCi are frustrated by structural and chemical obstructions in the damaged nervous tissue [5] . Spinal cord repair approaches typically lead to small functional gains. one feature that most of these approaches have in common is a poor axonal regeneration response, suggesting that promoting axonal regeneration, including synapse formation, is essential to achieve substantial functional repair after SCi. if so, it is rational to anticipate that effective spinal cord therapies will need to include interventions addressing the axon growth-inhibition that leads to the poor axonal growth responses. As introduced above, axonal regeneration is considered an important repair mechanism for the injured spinal cord. Therefore, this review focuses on materials that have shown most promise to elicit an axonal regeneration response to foster functional restoration after ...

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Section: Synthetic Polymersmentioning

confidence: 99%

“…HA) [107] ; biologically inert unless modified [106] Low cell adhesion without addition of functional groups (i.e. RGD) [110] Increased astrocyte infiltration [112] Not gel-forming, incompatible with contusion (PHPMA) PHPMA is non-biodegradable but has better biocompatibility than PHEMA because of its modified chemical structure [116] .…”

Section: Limitationsmentioning

confidence: 99%

Biomaterials for spinal cord repair

Haggerty

Oudega

2013

Neurosci. Bull.

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“…In this study, the effect of scaffolds with different complex structure was studied, demonstrating that open-path designs better promoted axonal regeneration, while closed designs resulted in the encapsulation of fibrous tissues and the enlargement of defects. Freeze-drying is another way to fabricate uniaxial hydrogel scaffolds [37,38]. With a gradient in temperature, scaffolds with honeycomb structure were created [38].…”

Section: Architecturementioning

confidence: 99%

Hyaluronic acid-based scaffold for central neural tissue engineering

Wang

et al. 2012

Interface Focus.

129

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Central nervous system (CNS) regeneration with central neuronal connections and restoration of synaptic connections has been a long-standing worldwide problem and, to date, no effective clinical therapies are widely accepted for CNS injuries. The limited regenerative capacity of the CNS results from the growth-inhibitory environment that impedes the regrowth of axons. Central neural tissue engineering has attracted extensive attention from multi-disciplinary scientists in recent years, and many studies have been carried out to develop cell-and regenerationactivating biomaterial scaffolds that create an artificial micro-environment suitable for axonal regeneration. Among all the biomaterials, hyaluronic acid (HA) is a promising candidate for central neural tissue engineering because of its unique physico-chemical and biological properties. This review attempts to outline current biomaterials-based strategies for CNS regeneration from a tissue engineering point of view and discusses the main progresses in research of HA-based scaffolds for central neural tissue engineering in detail.

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“…The solid-liquid separated solution was subsequently freeze dried. Stokols and Tuszynski also used a uniaxial thermal gradient with agarose to form linear channels (Stokols and Tuszynski 2004). These channels were continuous for up to 1cm and had pore sizes (channel diameter) on the order of 30-100m.…”

Section: Phase Separation and Selective Dissolutionmentioning

confidence: 99%

“…Other studies with hydrogels have shown promising outcomes. Stokols et al reported a unique agarose guidance scaffold consisting of long linear channels (Stokols and Tuszynski 2004). These constructs had pore diameters (channels) of 119±26m and were capable of sustained growth factor release.…”

Section: Nervous Systemmentioning

confidence: 99%