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

Abstract

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.

Nerve Guidance Conduits with Hierarchical Anisotropic Architecture for Peripheral Nerve Regeneration

“…[ 48–50 ] Electrospinning and unidirectional freeze drying have been applied to introduce filler alignment. [ 51,52 ] However, controlling luminal pore size without compromising anisotropy remains difficult for both electrospinning and unidirectional freeze drying. [ 49 ] Silk nanofibers composed of beta‐sheet rich structures have negative charges with a zeta potential of −31.4 ± 2.50 mv, endowing motility in electrical fields.…”

“…[48][49][50] Electrospinning and unidirectional freeze drying have been applied to introduce filler alignment. [51,52] However, controlling luminal pore size without compromising anisotropy remains difficult for both electrospinning and Figure 1. Fabrication of silk conduits with hierarchical silk nanofiber fillers: A) FTIR analysis a) before and b) after treatment at 60°C; B) mechanical properties of hollow silk conduits; C) photographs of the aligned hydrogels derived from 1% silk nanofiber solutions; D) SEM images of fillers derived from 1% silk nanofiber solutions; E) high magnification images of the lamellae of fillers; F) photographs of the aligned hydrogels derived from 2% silk nanofiber solutions; G) SEM images of fillers derived from 2% silk nanofiber solutions; H) high magnification images of the lamellae of fillers; I) photograph of the hollow silk conduits; J) photograph of the silk conduits filled with the aligned hydrogels; K) SEM images of silk conduits filled with silk nanofiber fillers.…”

Extracellular Matrix‐Mimetic Hydrogels for Treating Neural Tissue Injury: A Focus on Fibrin, Hyaluronic Acid, and Elastin‐Like Polypeptide Hydrogels

“…Many different biomaterials have been developed to modify the neural injury environment and promote subsequent axonal regeneration for the purpose of enabling functional recovery. [34][35][36][37][38][39][40] Hydrogels can be injected to fill irregular injury sites, used to deliver or sequester various molecules, and influence the activity of neural cells. [34,35,39] Hydrogels can also be implemented as intraluminal fillings in nerve guidance conduits to facilitate uniform cell infiltration as well as provide structural support to prevent conduit collapse.…”

Advanced Bio-Based Polymers for Astrocyte Cell Models

“…(A) The peripheral nervous system consists of Schwann cells (blue) that myelinate the axons of peripheral neurons (green). (B) The central nervous system consists of astrocytes (yellow) that regulate synaptic connections and comprise the blood-brain barrier, oligodendrocytes (blue) that myelinate axons of neurons, and microglia (purple), which act as resident innate immune cells [32].…”

“…Biomaterials that decrease GFAP expression are thought to favorably support neural regeneration. On the contrary, if the biomaterial increases GFAP expression, this implies a (B) The central nervous system consists of astrocytes (yellow) that regulate synaptic connections and comprise the blood-brain barrier, oligodendrocytes (blue) that myelinate axons of neurons, and microglia (purple), which act as resident innate immune cells [32].…”