Noncovalent Bonding of RGD and YIGSR to an Electrospun Poly(ε‐Caprolactone) Conduit through Peptide Self‐Assembly to Synergistically Promote Sciatic Nerve Regeneration in Rats

Abstract

The nerve conduit with biofunctionalities can regulate neurite outgrowth, as well as the migration, proliferation, and myelination activity of Schwann cells. In the present study, polycaprolactone (PCL) conduits are coated with Naphthalene-phenylalanine-phenylalanine-glycine-arginine-glycine-aspartic (Nap-FFGRGD) and Naphthalene-phenylalanine-phenylalanine-glycine-cysteine-aspartic-proline-glycine-tyrosine-isoleucine-glycine-serine-arginine (Nap-FFGCDPGYIGSR) by self-assembly. In vitro studies demonstrate that arginine-glycine-aspartic (RGD) and tyrosine-isoleucine-glycine-serine-arginine (YIGSR) are capable of synergistically enhancing the ability of PCL to support the adhesion and proliferation of Schwann cells, as well as increasing neurite outgrowth from dorsal root ganglions explants. This synergistic effect may occur via the activation of both the phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated protein kinase pathways. RGD/YIGSR modifications demonstrate beneficial effects across a 15 mm sciatic nerve gap in axonal regeneration and functional recovery. In addition, increased vascularization is observed in the RGD/YIGSR-PCL group, which might contribute to their beneficial effects on nerve regeneration. These findings indicate the potential of the RGD/YIGSR-PCL conduit to promote axonal regeneration and functional recovery, making the RGD/YIGSR-PCL conduit an attractive candidate for the treatment of a critical nerve defect.

Electrospun Fibrous Architectures for Drug Delivery, Tissue Engineering and Cancer Therapy

“…The application of electrospun scaffolds extends to both peripheral nerve injury, and central nervous system injury,[28a,167] which consists of traumatic brain injury168 and spinal cord injury. [33b,91,169] Those neurodegenerative diseases and traumatic nerve injuries vastly deteriorate the life quality and proper treatment methods are yet missing.…”

“…Aiming for bridging the defected nerve with a gap larger than 10 mm, Zhu et al produced a tubular PCL nerve conduit composed of electrospun microfibers. Peptide self‐assembled RGD and YIGSR layers were non‐covalently bonded to the obtained PCL fibers and were expected to improve the biocompatibility of hydrophobic PCL fibers ( Figure a,b).…”

“…c) The gross view of the regenerated nerve, toluidine blue staining of regenerated axons, TEM of regenerated axon, and myelin sheath at middle portion in all groups at 12 weeks after surgery: c1,6,11,16) autograft group, c2,7,12,17) control group, c3,8,13,18) RGD group, c4,9,14,19) YIGSR group, and c5,10,15,20) RGD/YIGSR group. Reproduced with permission . Copyright 2017, John Wiley and Sons.…”

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

“…Also, it has been shown that a PCL conduit can improve motor functional recovery by increase in sciatic functional index (SFI) values, recovery in muscle atrophy, and increase in number of regenerated axons in the sciatic nerve gaps due to creating proper porosity and increase of vascularization in the implanted site (Pixley et al, ; Zhu et al, ). Therefore, this polymer can be considered as one of the most suitable candidates for fabricating the neural conduit.…”

Tubular electrospun scaffolds tested in vivo for tissue engineering

“…This team concluded that PCL scaffolds may be improved by the use of RGD/YIGSR peptides. 25 One of the possible modifications of the electrospinning technique is the fabrication of a layered scaffold, which can regulate degradation time and improve mechanical/biological properties. Chung J et al in 2014 made tubular scaffolds of three layers: internal and external layers made of polycaprolactone and a middle layer made of silk fibroin.…”