Advances in Electrospun Nerve Guidance Conduits for Engineering Neural Regeneration

Abstract

Injuries to the peripheral nervous system result in devastating consequences with loss of motor and sensory function and lifelong impairments. Current treatments have largely relied on surgical procedures, including nerve autografts to repair damaged nerves. Despite improvements to the surgical procedures over the years, the clinical success of nerve autografts is limited by fundamental issues, such as low functionality and mismatching between the damaged and donor nerves. While peripheral nerves can regenerate to some extent, the resultant outcomes are often disappointing, particularly for serious injuries, and the ongoing loss of function due to poor nerve regeneration is a serious public health problem worldwide. Thus, a successful therapeutic modality to bring functional recovery is urgently needed. With advances in three-dimensional cell culturing, nerve guidance conduits (NGCs) have emerged as a promising strategy for improving functional outcomes. Therefore, they offer a potential therapeutic alternative to nerve autografts. NGCs are tubular biostructures to bridge nerve injury sites via orienting axonal growth in an organized fashion as well as supplying a supportively appropriate microenvironment. Comprehensive NGC creation requires fundamental considerations of various aspects, including structure design, extracellular matrix components and cell composition. With these considerations, the production of an NGC that mimics the endogenous extracellular matrix structure can enhance neuron–NGC interactions and thereby promote regeneration and restoration of function in the target area. The use of electrospun fibrous substrates has a high potential to replicate the native extracellular matrix structure. With recent advances in electrospinning, it is now possible to generate numerous different biomimetic features within the NGCs. This review explores the use of electrospinning for the regeneration of the nervous system and discusses the main requirements, challenges and advances in developing and applying the electrospun NGC in the clinical practice of nerve injuries.

Light-to-Heat Converting ECM-Mimetic Nanofiber Scaffolds for Neuronal Differentiation and Neurite Outgrowth Guidance

“…This allows the fibers to be transferred to any target substrates, regardless of their material, and also, potentially, to form bundles from individual fibers suitable for filling hollow nerve guidance conduits used for nerve regeneration. A similar design utilizing bundles of micron fibers inside a polymer tube has already been successfully applied for peripheral nerve regeneration in vivo [13]. Photothermal scaffolds made of fibrous materials were previously fabricated by electrospinning with the addition of light-converting particles to the polymer solution.…”

“…Several studies reported preparation and successful application of artificial nerve conduits based on electrospun fibrous materials in biological test systems [13,62,63]. However, relatively few works are deploying fiber nanomaterials with fiber diameters of 100 nm due to technical difficulties of manufacturing [42].…”

“…Natural extracellular matrix (ECM) architectures and topographies affect neural cell properties and functions, such as cell migration, differentiation, and morphology through contact guidance, carried out by mechanical (topology) and biochemical cues [11]. The ability to mimic the architecture of natural ECM, combined with the large specific area of fibrous material, allow nanocomposite scaffolds to encourage neuron growth [12][13][14]. When designing ECM-mimetic scaffolds, it is necessary to take into account the dimensions of the structural components of the neural ECM; e.g., collagen fibrils of individual endoneurium have an average diameter of 41.31 ± 4.2 nm and 30-60 nm in perineurium layer [15].…”

Recent advances in PLLA-based biomaterial scaffolds for neural tissue engineering: Fabrication, modification, and applications

“…Additionally, PLLA can be easily blended with other materials or bioactive polymers to optimize its surface bioactivity ( Jahromi et al, 2020 ; Siriwardane et al, 2021 ). Furthermore, PLLA-based materials can be fabricated into two-dimensional or three-dimensional (3D) scaffolds with stable nanofibrous and porous topology which provide the biomimetic structures for nerve cell adhesion and growth while supporting neural tissue formation ( Almansoori et al, 2020 ; Behtaj et al, 2022 ; Weir et al, 2022 ). Moreover, PLLA-based scaffolds have the potential to be combined with various therapeutic approaches such as drug delivery, electrical stimulation, magnetic stimulation, and stem cell therapy, which have been explored in nerve repair and regeneration ( Zhang et al, 2017 ; Chen et al, 2020 ; Jedari et al, 2020 ; Rahimi-Sherbaf et al, 2020 ; Tonellato et al, 2020 ).…”

Electrospun Materials for Biomedical Applications

“…St. John et al, in their review entitled “Advances in Electrospun Nerve Guidance Conduits for Engineering Neural Regeneration”, reported the capability of the electrospun approach to fabricate fibers of various scales and which have a large surface area with a three-dimensional porous structure resembling the native extracellular matrix for regeneration of the nervous system [ 21 ]. Considerations regarding conditions of the injury, as well as the requirements and structure for the nerve guidance conduits, were also discussed.…”