Fluid shear in viscous fibronectin gels allows aggregation of fibrous materials for CNS tissue engineering

Phillips, James B.; King, Von R.; Ward, Zoe; Porter, Rebecca A.; Priestley, John V.; Brown, Robert A.

doi:10.1016/j.biomaterials.2003.09.052

Cited by 44 publications

(25 citation statements)

References 44 publications

(69 reference statements)

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“…However, these aggregates seemed to be mediated by disulfide bonding of two free cysteines, which are not involved in native FN fibril formation (12). When FN is partially denatured and sheared in solution, the FN aggregates into mats with a distinctly fibrillar substructure (13)(14)(15). An intriguing alternative method of fibril formation involved pulling fibrils from the surface of a FN solution.…”

Section: Fibronectin (Fn)mentioning

confidence: 99%

Domain Unfolding Plays a Role in Superfibronectin Formation

Ohashi

Erickson

2005

Journal of Biological Chemistry

103

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Superfibronectin (sFN) is a fibronectin (FN) aggregate that is formed by mixing FN with anastellin, a fragment of the first type III domain of FN. However, the mechanism of this aggregation has not been clear. In this study, we found that anastellin co-precipitated with FN in a ratio of ϳ4:1, anastellin:FN monomer. The primary binding site for anastellin was in the segment III 1-3, which bound three molecules of anastellin and was able to form a precipitate without the rest of the FN molecule. Anastellin binding to III 3 caused a conformational change in that domain that exposed a cryptic thermolysin-sensitive site. An additional anastellin binds to III 11, where it enhances thermolysin digestion of III 11. An engineered disulfide bond in III 3 inhibited both aggregation and protease digestion, suggesting that the stability of III 3 is a key factor in sFN formation. We propose a three-step model for sFN formation: 1) FN-III domains spontaneously unfold and refold; 2) anastellin binds to an unfolded domain, preventing its refolding and leaving it with exposed hydrophobic surfaces and ␤-sheet edges; and 3) these exposed elements bind to similar exposed elements on other molecules, leading to aggregation. The model is consistent with our observation that the kinetics of aggregation are first order, with a reaction time of 500 -700 s. Similar mechanisms may contribute to the assembly of the native FN matrix. Fibronectin (FN)2 is an extracellular matrix protein and is also present in a soluble form in blood and tissue fluid (1). Soluble, dimeric FN molecules assemble into an insoluble supramolecular structure known as the FN matrix, which appears during embryonic development, wound healing, and also in cell culture (1). The biological importance of FN during development and wound healing has been demonstrated by generating conventional and conditional FN knock-out mice and alternative splicing domain (EDA) knock-out and knock-in mice (2-4).FN matrix fibrils may be one of the least understood macromolecular protein assemblies. Whereas a large number of protein structures can be self-assembled from purified subunits (e.g. microtubules, actin filaments, collagen fibrils, and viruses capsids), FN fibrils have only been produced by living cells in culture. The cells in tissue culture can assemble FN matrix fibrils either from FN that they synthesize or from soluble FN added exogenously. Fibril assembly takes place on the cell surface and requires integrins (5-9).A fundamental deficit is our lack of knowledge of the structure of FN fibrils. FN molecules must be attached to each other to form the fibrils, but we do not know even the sites of contact between molecules nor the types of bonds that hold them together. Several attempts at in vitro assembly of FN have resulted in aggregates that may be related to FN matrix fibrils. For instance, aggregates could be formed when FN was partially denatured in guanidine HCl and incubated over time (10, 11). However, these aggregates seemed to be mediated by disulfide bonding of two f...

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Section: Fibronectin (Fn)mentioning

confidence: 99%

Domain Unfolding Plays a Role in Superfibronectin Formation

Ohashi

Erickson

2005

Journal of Biological Chemistry

103

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“…For PNS injury, implantation of FN mats impregnated with NT-3, but not naive FN mats, after rat sciatic nerve transection showed a beneficial effect on neuromuscular interaction and induced a significant number of myelinated axons into the scaffolds at 8 months (Sterne et al, 1997). In contrast, in SCI, FN mats containing neurotrophic factors such as NT-3, BDNF, or nerve growth factor (NGF) did not stimulate axonal outgrowth from the graft into the host spinal cord (King et al, 2004), although plain FN acted as a guidance cue for some axonal regrowth from the host spinal cord (Phillips et al, 2004). In addition, the implantation of anti-transforming growth factor ␤2 (TGF␤2)-incubated FN mats failed to enhance axonal regeneration after partial spinal cord transection (King et al, 2004).…”

Section: Degradable Biomaterialsmentioning

confidence: 99%

Bioengineered Strategies for Spinal Cord Repair

Nomura

Tator

Shoichet

2006

Journal of Neurotrauma

183

122

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This article reviews bioengineered strategies for spinal cord repair using tissue engineered scaffolds and drug delivery systems. The pathophysiology of spinal cord injury (SCI) is multifactorial and multiphasic, and therefore, it is likely that effective treatments will require combinations of strategies such as neuroprotection to counteract secondary injury, provision of scaffolds to replace lost tissue, and methods to enhance axonal regrowth, synaptic plasticity, and inhibition of astrocytosis. Biomaterials have major advantages for spinal cord repair because of their structural and chemical versatility. To date, various degradable or non-degradable biomaterial polymers have been tested as guidance channels or delivery systems for cellular and non-cellular neuroprotective or neuroregenerative agents in experimental SCI. There is promise that bioengineering technology utilizing cellular treatment strategies, including Schwann cells, olfactory ensheathing glia, or neural stem cells, can promote repair of the injured spinal cord. This review is divided into three parts: (1) degradable and non-degradable biomaterials; (2) device design; and (3) combination strategies with scaffolds. We will show that bioengineering combinations of cellular and non-cellular strategies have enhanced the potential for experimental SCI repair, although further pre-clinical work is required before this technology can be translated to humans.

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“…It is found in its soluble form in blood and participates in wound healing process. It can be aggregated to form mats, which can be used as scaffolds for the repair of neural tissue [69][70][71][72][73][74]. These mats contain pores that all orient in the same direction to allow for guidance of regenerating neurons, provide cell adhesion sites, and can absorb growth factors, storing them as reservoir.…”

Section: Synthetic Materials-syntheticmentioning

confidence: 99%

Approaches to neural tissue engineering using scaffolds for drug delivery

Willerth

Sakiyama‐Elbert

2007

Advanced Drug Delivery Reviews

334

249

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This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented.

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Fluid shear in viscous fibronectin gels allows aggregation of fibrous materials for CNS tissue engineering

Cited by 44 publications

References 44 publications

Domain Unfolding Plays a Role in Superfibronectin Formation

Domain Unfolding Plays a Role in Superfibronectin Formation

Bioengineered Strategies for Spinal Cord Repair

Approaches to neural tissue engineering using scaffolds for drug delivery

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