The potential of Antheraea pernyi silk for spinal cord repair

A Varone,A M Rajnicek,F Vollrath,W Huang,D Knight,S Lesage

doi:10.1038/s41598-017-14280-5

A Varone, A M Rajnicek + Show 4 more

Open Access

https://doi.org/10.1038/s41598-017-14280-5

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Journal: Scientific Reports	Publication Date: Oct 23, 2017
Citations: 16	License type: open-access

Affiliation: University of Oxford, University of Aberdeen

Abstract

One of the most challenging applications for tissue regeneration is spinal cord damage. There is no cure for this, partly because cavities and scar tissue formed after injury present formidable barriers that must be crossed by axons to restore function. Natural silks are considered increasingly for medical applications because they are biocompatible, biodegradable and in selected cases promote tissue growth. Filaments from wild Antheraea pernyi silkworms can support axon regeneration in peripheral nerve injury. Here we presented evidence that degummed A. pernyi filaments (DAPF) support excellent outgrowth of CNS neurons in vitro by cell attachment to the high density of arginine-glycine-aspartic acid tripeptide present in DAPF. Importantly, DAPF showed stiffness properties that are well suited to spinal cord repair by supporting cell growth mechano-biology. Furthermore, we demonstrated that DAPF induced no activation of microglia, the CNS resident immune cells, either in vitro when exposed to DAPF or in vivo when DAPF were implanted in the cord. In vitro DAPF degraded gradually with a corresponding decrease in tensile properties. We conclude that A. pernyi silk meets the major biochemical and biomaterial criteria for spinal repair, and may have potential as a key component in combinatorial strategies for spinal repair.

Highlights

One of the most challenging applications for tissue regeneration is spinal cord damage
To assess whether degummed A. pernyi filaments (DAPF) promoted cell adhesion and guided neurite growth, we studied the interactions of primary neuron cultures with DAPF using CNS neurons derived from postnatal rat cortex (Figs 1 and 2 and Supplementary Fig. S3) and from embryonic Xenopus spinal cord neurons (Supplementary Fig. S3)
Analysis of the interactions between DAPF and CNS neurons located within a distance of 100 μm of the silk filaments showed that the percentage of neurons with their cell bodies attached to DAPF, i.e. physically interacting with the filaments, was significantly higher than that of neurons with their cell bodies attached to the coverslips, i.e. not physically interacting with the filaments (Supplementary Fig. S3a,b)

Summary

Introduction

One of the most challenging applications for tissue regeneration is spinal cord damage. ® In our previous work degummed A. pernyi filaments (DAPF) known as Spidrex silk filaments promoted significant axonal regeneration and functional recovery in a rat model of sciatic nerve injury[10] This prompted us to investigate here whether DAPF have all the relevant properties considered to be key criteria in biomaterial design for spinal cord repair[12,13]. These include: (1) a surface chemistry and topography to facilitate cell adhesion and provide guidance to axonal extension; (2) a minimal host immune response; (3) a stiffness approximating that of www.nature.com/scientificreports/. We report that DAPF appear to fulfil all these criteria suggesting that DAPF as part of a combinatorial strategy may promote axon regeneration and functional recovery after spinal cord injury

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Conclusion