Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension and Decrease Schwann Cell Expression of Promyelinating Factors

Puhl, Devan L; Funnell, Jessica L; D’Amato, Anthony R.; Bao, Jonathan; Zagorevski, Dmitri V.; Pressman, Yelena; Morone, Daniel; Haggerty, Agnes E.; Oudega, Martin; Gilbert, Ryan J.

doi:10.3389/fbioe.2020.00937

Cited by 11 publications

(12 citation statements)

References 74 publications

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“…For this reason, in this study for the first time to our knowledge, electrospun ha-PLGA scaffolds, designed for tendon TE, were subjected to hydrolytic degradation under di-H 2 O and PBS conditions at 37 • C and evaluated for up to 20 weeks. Of note, tendons regenerate at a slow healing rate, which necessitated performing the degradation study up to 20 weeks, compared to most other studies that usually conducted similar experiments on electrospun ha-PLGA constructs for no longer than 4 to 8 weeks [56][57][58][59][60][61][62]. The changes in scaffolds' morphology, mass, liquid uptake, molecular weight, and distribution, as well as their mechanical properties, together with the changes in pH and conductivity, were investigated systematically.…”

Section: Discussionmentioning

confidence: 99%

Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro

Khatib

Russo

Prencipe

et al. 2021

Cells

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Electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds with highly aligned fibers (ha-PLGA) represent promising materials in the field of tendon tissue engineering (TE) due to their characteristics in mimicking fibrous extracellular matrix (ECM) of tendon native tissue. Among these properties, scaffold biodegradability must be controlled allowing its replacement by a neo-formed native tendon tissue in a controlled manner. In this study, ha-PLGA were subjected to hydrolytic degradation up to 20 weeks, under di-H2O and PBS conditions according to ISO 10993-13:2010. These were then characterized for their physical, morphological, and mechanical features. In vitro cytotoxicity tests were conducted on ovine amniotic epithelial stem cells (oAECs), up to 7 days, to assess the effect of non-buffered and buffered PLGA by-products at different concentrations on cell viability and their stimuli on oAECs’ immunomodulatory properties. The ha-PLGA scaffolds degraded slowly as evidenced by a slight decrease in mass loss (14%) and average molecular weight (35%), with estimated degradation half-time of about 40 weeks under di-H2O. The ultrastructure morphology of the scaffolds showed no significant fiber degradation even after 20 weeks, but alteration of fiber alignment was already evident at week 1. Moreover, mechanical properties decreased throughout the degradation times under wet as well as dry PBS conditions. The influence of acid degradation media on oAECs was dose-dependent, with a considerable effect at 7 days’ culture point. This effect was notably reduced by using buffered media. To a certain level, cells were able to compensate the generated inflammation-like microenvironment by upregulating IL-10 gene expression and favoring an anti-inflammatory rather than pro-inflammatory response. These in vitro results are essential to better understand the degradation behavior of ha-PLGA in vivo and the effect of their degradation by-products on affecting cell performance. Indeed, buffering the degradation milieu could represent a promising strategy to balance scaffold degradation. These findings give good hope with reference to the in vivo condition characterized by physiological buffering systems.

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Section: Discussionmentioning

confidence: 99%

Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro

Khatib

Russo

Prencipe

et al. 2021

Cells

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“…In addition to functionalizing the surface of electrospun fibers, therapeutic molecules such as small-molecule drugs, proteins, and nucleic acids (e.g., DNA, miRNA, and siRNA) can be immobilized onto the surface or encapsulated within electrospun fibers to allow for prolonged, local therapeutic delivery [ 154 , 155 ]. Small-molecule drug-loaded electrospun fibers can be utilized to alter Schwann cell activity or affect the Schwann cell maturation state [ 156 , 157 ]. For example, Bhutto et al fabricated an aligned poly ( l -lactic acid-co-caprolactone)/silk fibroin fiber mesh loaded with vitamin B5 via blend electrospinning and observed greater Schwann cell proliferation and dispersion across the entirety of the scaffold compared to unloaded control fibers.…”

Section: Peripheral Nervous System Glia and Electrospun Fibersmentioning

confidence: 99%

“…In another study, Puhl et al found that the incorporation of the drug fingolimod hydrochloride, known to shift Schwann cells to an immature repair state—into highly aligned PLGA electrospun fibers—increased Schwann cell migration compared with control PLGA fibers. Additionally, the sustained release of fingolimod reduced the Schwann cell expression of mature, promyelinating markers [ 157 ]. Following injury or in a disease state, the PNS can be subjected to various forms of stress that can lead to increased Schwann cell death [ 158 ].…”

Section: Peripheral Nervous System Glia and Electrospun Fibersmentioning

confidence: 99%

Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

et al. 2020

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Electrospinning is a fabrication technique used to produce nano- or micro- diameter fibers to generate biocompatible, biodegradable scaffolds for tissue engineering applications. Electrospun fiber scaffolds are advantageous for neural regeneration because they mimic the structure of the nervous system extracellular matrix and provide contact guidance for regenerating axons. Glia are non-neuronal regulatory cells that maintain homeostasis in the healthy nervous system and regulate regeneration in the injured nervous system. Electrospun fiber scaffolds offer a wide range of characteristics, such as fiber alignment, diameter, surface nanotopography, and surface chemistry that can be engineered to achieve a desired glial cell response to injury. Further, electrospun fibers can be loaded with drugs, nucleic acids, or proteins to provide the local, sustained release of such therapeutics to alter glial cell phenotype to better support regeneration. This review provides the first comprehensive overview of how electrospun fiber alignment, diameter, surface nanotopography, surface functionalization, and therapeutic delivery affect Schwann cells in the peripheral nervous system and astrocytes, oligodendrocytes, and microglia in the central nervous system both in vitro and in vivo. The information presented can be used to design and optimize electrospun fiber scaffolds to target glial cell response to mitigate nervous system injury and improve regeneration.

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“…There have been numerous subsequent studies that have used a wide variety of materials to explore what topographical or biochemical features are best suited to support directional growth of neurites as well as the alignment of glial cells that, in turn, would support such growth. This literature is extensive and has been reviewed by several investigators [154,156,157,166,167]. One of the overarching conclusions that can be gleaned from these studies is that aligned substrates, whatever means by which they are produced, exert compelling directional cues for growing neurites.…”

Section: Reconstruction Of Tissue Geometry To Promote Regenerationmentioning

confidence: 99%

The Role of Tissue Geometry in Spinal Cord Regeneration

et al. 2022

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Unlike peripheral nerves, axonal regeneration is limited following injury to the spinal cord. While there may be reduced regenerative potential of injured neurons, the central nervous system (CNS) white matter environment appears to be more significant in limiting regrowth. Several factors may inhibit regeneration, and their neutralization can modestly enhance regrowth. However, most investigations have not considered the cytoarchitecture of spinal cord white matter. Several lines of investigation demonstrate that axonal regeneration is enhanced by maintaining, repairing, or reconstituting the parallel geometry of the spinal cord white matter. In this review, we focus on environmental factors that have been implicated as putative inhibitors of axonal regeneration and the evidence that their organization may be an important determinant in whether they inhibit or promote regeneration. Consideration of tissue geometry may be important for developing successful strategies to promote spinal cord regeneration.

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Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension and Decrease Schwann Cell Expression of Promyelinating Factors

Cited by 11 publications

References 74 publications

Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro

Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro

Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

The Role of Tissue Geometry in Spinal Cord Regeneration

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