3D Fabrication with Integration Molding of a Graphene Oxide/Polycaprolactone Nanoscaffold for Neurite Regeneration and Angiogenesis

Abstract

Treating peripheral nerve injury faces major challenges and may benefit from bioactive scaffolds due to the limited autograft resources. Graphene oxide (GO) has emerged as a promising nanomaterial with excellent physical and chemical properties. GO has functional groups that confer biocompatibility that is better than that of graphene. Here, GO/polycaprolactone (PCL) nanoscaffolds are fabricated using an integration molding method. The nanoscaffolds exhibit many merits, including even GO nanoparticle distribution, macroporous structure, and strong mechanical support. Additionally, the process enables excellent quality control. In vitro studies confirm the advantages of the GO/PCL nanoscaffolds in terms of Schwann cell proliferation, viability, and attachment, as well as neural characteristics maintenance. This is the first study to evaluate the in vivo performance of GO‐based nanoscaffolds in this context. GO release and PCL biodegradation is analyzed after long‐term in vivo study. It is also found that the GO/PCL nerve guidance conduit could successfully repair a 15 mm sciatic nerve defect. The pro‐angiogenic characteristic of GO is evaluated in vivo using immunohistochemistry. In addition, the AKT‐endothelial nitric oxide synthase (eNOS)‐vascular endothelial growth factor (VEGF) signaling pathway might play a major role in the angiogenic process. These findings demonstrate that the GO/PCL nanoscaffold efficiently promotes functional and morphological recovery in peripheral nerve regeneration, indicating its promise for tissue engineering applications.

A study on graphene composites for peripheral nerve injury repair under electrical stimulation

“…The noted importance of SC participation in PNI repair make SCs an attractive addition to articial nerve gras. 36 Our goals ought to evaluate the sensitivity of SCs to electrical cues in vitro that could better promote axonal growth and other related neural behaviors for PNI repair. By preparing a conductive graphenebased composite membrane with excellent electrical and mechanical property, we demonstrated that SC proliferation can be prompted through appropriate ES.…”

Enhancement of sciatic nerve regeneration with dual delivery of vascular endothelial growth factor and nerve growth factor genes

“…Therefore, here we did not observe there exist biologically synergistic recovery effect between VEGF and NGF. However, we think it may be caused by the short term recovery time we used in this study (4 weeks), as it's usually reported to last for 8 weeks or even longer for nerve recovery [8,9].…”

“…Peripheral sciatic nerve crush injury model was established on Sprague Dawley (SD) rats to evaluate the therapeutic effect of PDAPEI/pDNA polyplexes. All surgical operations followed instructions in published studies [8,9,35,36]. Briefly, SD rats (weight of 150 ± 10 g) were maintained in the SPF environment for 1 week and then anesthetized by 10% chloral hydrate (0.3 mL/kg) via intraperitoneal injection.…”

“…However, problems of low success rate of surgery, limited supply of donor nerves, insufficiency in large nerve gaps and inherent damage to donor Fang et al J Nanobiotechnol (2020) 18:46 sites have posed a huge challenge to the clinical use of autologous nerve grafting [6,7]. Currently, recovery with tissue-engineered methods is gradually becoming an alternative strategy for sciatic nerve reconstruction [8][9][10]. However, after having an overview of reported studies on tissue-engineered nerve grafting, we found that most pre-clinical researches focused on the role of neurogenesis in the peripheral nerve recovery, while the angiogenesis effect of blood vessels were often ignored [11].…”

Multilayered spraying and gradient dotting of nanodiamond–polycaprolactone guidance channels for restoration of immune homeostasis

“…We also discussed GO/PCL conduits via integration molding and evaluated their potential in stimulating angiogenesis to promote sciatic nerve defect repair. The possible mechanism was via vascular endothelial growth factor (VEGF) signaling 11 . Although they can effectively repair nerve injury, graphene-loaded nerve scaffolds are generally not very biocompatible, which limits their biomedical application.…”