Peripheral nerve injury is an important cause of disability, that can hinder significantly sensory and motor function. The clinical gold standard for peripheral nerve repair is the use of autografts, nevertheless, this method has limitations such as donor site morbidity. An emerging alternative to autografts are nerve guide conduits, which are used to entubulate the severed nerve and provide guidance for the directed regeneration of the nerve tissue. These nerve guide conduits are less effective than autografts, and to enhance their performance the incorporation of neurotrophins can be considered. To enable optimal nerve regeneration, it is important to continuously stimulate neurite outgrowth by designing a delivery system for the sustained delivery of neurotrophins. The aim of this study was to develop a novel bioactive surface on electrospun fibres to supply a sustained release of heparin bound NGF or BDNF electrostatically immobilised onto an amine functionalized surface to encourage neurite outgrowth and Schwann cell migration. The bioactive surface was characterised by XPS analysis and ELISA. To assess the effect of the bioactive surface on electrospun fibres, primary chick embryo dorsal root ganglia were used, and neurite outgrowth and Schwann cell migration were measured. Our results showed a significant improvement regarding nerve regeneration, with the growth of neurites of up to 3 mm in 7 days, accompanied by Schwann cells. We hypothesize that the physical guidance provided by the fibres along the sustained delivery of NGF or BDNF created a stimulatory environment for nerve regeneration. Our results were achieved by immobilising relatively low concentrations of neurotrophins (1 ng/ml), which provides a promising, low-cost, and scalable method to improve current nerve guide conduits.

Treatment for peripheral nerve injuries includes the use of autografts and nerve guide conduits (NGCs). However, outcomes are limited, and full recovery is rarely achieved. The use of nerve scaffolds as a platform to surface immobilize neurotrophic factors and deliver locally is a promising approach to support neurite and nerve outgrowth after injury. We report on a bioactive surface using functional amine groups, to which heparin binds electrostatically. X‐ray photoelectron spectroscopy analysis was used to characterize the presence of nitrogen and sulfur. Nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) were bound by electrostatic interaction to heparin, and the release profile evaluated by enzyme‐linked immunosorbent assay, which showed that ca. 1% of NGF was released from each of the bioactive surface within 7 days. Furthermore, each surface showed a maximum release of 97% of BDNF. Neurotrophin release on neurite outgrowth was evaluated by primary dorsal root ganglion with a maximum neurite growth response in vitro of 1,075 µm detected for surfaces immobilized with NGF at 1 ng/ml. In summary, the study reports on the design and construction of a biomimetic platform to deliver NGF and BDNF using physiologically low concentrations of neurotrophin. The platform is directly applicable and scalable for improving the regenerative ability of existing NGCs and scaffolds.

Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor. This splicing enables mRNA from a single gene to synthesize different proteins, which have different cellular properties and functions and yet arise from the same single gene. A family of splicing factors, Serine-arginine rich proteins, are needed to initiate the assembly and activation of the spliceosome. Serine and arginine rich splicing factor 1, part of the arginine/serine-rich splicing factor protein family, can either activate or inhibit the splicing of mRNAs, depending on the phosphorylation status of the protein and its interaction partners. Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor, this protein has been studied widely to identify its various roles in different diseases. Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection, showing its promising potential use in therapeutics for neurodegenerative disorders. Furthermore, serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases. In this review, we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection. In addition, we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders, as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.

The specialized role of the Schwann cell is reviewed in the context of peripheral nerve, spanning neural development, anatomy, signaling, and function. A particular focus of this chapter is the increasingly important role identified in many studies of Schwann cells in nerve injury and repair. We summarize a range of key studies describing these specialized roles, which include the alignment of