Abstract
Numerous nanostructured synthetic scaffolds mimicking the architecture of the natural extracellular matrix (ECM) have been described, but the polymeric nanofibers comprising the scaffold were substantially thicker than the natural collagen nanofibers of neural ECM. Here, we report neuron growth on electrospun scaffolds of nylon-4,6 fibers with an average diameter of 60 nm, which closely matches the diameter of collagen nanofibers of neural ECM, and compare their properties with the scaffolds of thicker 300 nm nanofibers. Previously unmodified nylon was not regarded as an independent nanostructured matrix for guided growth of neural cells; however, it is particularly useful for ultrathin nanofiber production. We demonstrate that, while both types of fibers stimulate directed growth of neuronal processes, ultrathin fibers are more efficient in promoting and accelerating neurite elongation. Both types of scaffolds also improved synaptogenesis and the formation of connections between hippocampal neurons; however, the mechanisms of interaction of neurites with the scaffolds were substantially different. While ultrathin fibers formed numerous weak immature β1-integrin-positive focal contacts localized over the entire cell surface, scaffolds of submicron fibers formed β1-integrin focal adhesions only on the cell soma. This indicates that the scaffold nanotopology can influence focal adhesion assembly involving various integrin subunits. The fabricated nanostructured scaffolds demonstrated high stability and resistance to biodegradation, as well as absence of toxic compound release after 1 month of incubation with live cells in vitro. Our results demonstrate the high potential of this novel type of nanofibers for clinical application as substrates facilitating regeneration of nervous tissue.
Highlights
Various types of peripheral nerve damage are known to be widespread and often lead to loss of sensation, organ, and muscle innervation, which can cause disability [1]
Information)has has shown that no toxic products were formed by the nylon scaffold after a month of expo‐to shown that no toxic products were formed by the nylon scaffold after a month of exposure sure to collagenase, theenzyme main enzyme of the extracellular matrixS2)
Scaffolds formed by 60 nm diameter ultrathin nylon nanofibers with both random and aligned fiber orientation were fabricated by electrospinning
Summary
Various types of peripheral nerve damage are known to be widespread and often lead to loss of sensation, organ, and muscle innervation, which can cause disability [1]. In cases of extensive damage, autologous nerve grafts were used to connect the damaged ends of the nerve fibers without tension The disadvantages of this approach include, but are not limited to, the need for additional surgery; slow rates of regeneration, which can lead to degeneration of target-end-organ after prolonged periods of denervation; inability in some cases to detect the proximal end of the damaged nerve; low numbers of damaged neurons sprouting through the donor tissue, which leads to incomplete restoration of functions and frequent pain [2]. The limitations are related, in particular, to the longer time required to vascularize the longer grafts This can lead to the formation of an ischemic environment inside the graft and decrease the release of neurotrophic factors due to Schwann cell senescence, which inhibits axon regeneration.
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