Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries

Straley, Karin; Foo, Cheryl Wong Po; Heilshorn, Sarah C.

doi:10.1089/neu.2009.0948

Cited by 305 publications

(259 citation statements)

References 195 publications

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“…Such synergistic approaches have the potential to regenerate the injured spinal cord with varying degrees of efficacy, but none have been successfully translated into the clinic [41]. The full potential of combinatorial strategies utilising aligned nanofibers with combinations of cells and biomolecules has yet to be elucidated, due in part to a heavy reliance on in vivo SCI models, in the absence of highthroughput, biologically-relevant in vitro screening models of SCI [5,42]. Two-dimensional reductionist tools in current widespread use e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The latter is a destructive, multifaceted condition, with a poor clinical prognosis for functional recovery [2,3]. Strategically, such scaffolds can aid regeneration by providing aligned topographies, gradients of chemical guidance cues and transplant cell populations to replace lost/damaged cells [4][5][6]. Evaluation and optimization of synthetic bridges is currently the subject of intensive research globally, with the developmental testing of novel scaffolds and constructs being heavily reliant on live animal injury models [7].…”

Section: Introductionmentioning

confidence: 99%

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An in vitro spinal cord injury model to screen neuroregenerative materials

Weightman¹,

Pickard²,

Yang³

et al. 2014

Biomaterials

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Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, biocompatibility, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a novel solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofiber meshes (± poly-lysine + laminin coating) within injury sites using a lightweight

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An in vitro spinal cord injury model to screen neuroregenerative materials

Weightman¹,

Pickard²,

Yang³

et al. 2014

Biomaterials

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“…Here, we focus on potential applications in the central nervous system. Unlike many other tissues, the adult central nervous system has a limited capacity for self-repair (35). Transplantation of many cell types including endothelial cells (36) and adult neural stem cells (37) have produced partial functional recovery in animal models with a wide spectrum of lesions.…”

mentioning

confidence: 99%

Two-component protein-engineered physical hydrogels for cell encapsulation

Foo

Lee

Mulyasasmita

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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288

255

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Current protocols to encapsulate cells within physical hydrogels require substantial changes in environmental conditions (pH, temperature, or ionic strength) to initiate gelation. These conditions can be detrimental to cells and are often difficult to reproduce, therefore complicating their use in clinical settings. We report the development of a two-component, molecular-recognition gelation strategy that enables cell encapsulation without environmental triggers. Instead, the two components, which contain multiple repeats of WW and proline-rich peptide domains, undergo a sol-gel phase transition upon simple mixing and hetero-assembly of the peptide domains. We term these materials mixing-induced, two-component hydrogels. Our results demonstrate use of the WW and proline-rich domains in protein-engineered materials and expand the library of peptides successfully designed into engineered proteins. Because both of these association domains are normally found intracellularly, their molecular recognition is not disrupted by the presence of additional biomolecules in the extracellular milieu, thereby enabling reproducible encapsulation of multiple cell types, including PC-12 neuronal-like cells, human umbilical vein endothelial cells, and murine adult neural stem cells. Precise variations in the molecular-level design of the two components including (i) the frequency of repeated association domains per chain and (ii) the association energy between domains enable tailoring of the hydrogel viscoelasticity to achieve plateau shear moduli ranging from Ϸ9 to 50 Pa. Because of the transient physical crosslinks that form between association domains, these hydrogels are shear-thinning, injectable, and self-healing. Neural stem cells encapsulated in the hydrogels form stable three-dimensional cultures that continue to self-renew, differentiate, and sprout extended neurites.biomaterial ͉ cell transplantation ͉ protein engineering

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“…Varying the composition of these co-polymers allows for precise control of degradation and mechanical properties [136] ; however, this class of polymers does not form hydrogels. Therefore their use is limited to conduits for complete transection.…”

Section: Poly-ethylene-glycol (Peg)/poly-ethylene Oxide (Peo)mentioning

confidence: 99%

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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Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries

Cited by 305 publications

References 195 publications

An in vitro spinal cord injury model to screen neuroregenerative materials

An in vitro spinal cord injury model to screen neuroregenerative materials

Two-component protein-engineered physical hydrogels for cell encapsulation

Biomaterials for spinal cord repair

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