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

Abstract

The major problem in peripheral nerve repair is restoration of the microenvironment rather than traditional structural reconstruction. Nanodiamonds (NDs), highly biocompatible carbon nanoparticles, are widely applied in medical engineering. They may alleviate inflammatory insults in peripheral nerve injury because they can induce macrophage polarization from a proinflammatory to an anti-inflammatory state. Here we report a concentric multilayered spraying manufacturing process to fabricate microporous ND/polycaprolactone (PCL) nerve bridges. We investigated the proliferative, adhesive, and glioprotective role of these bridges in Schwann cells in vitro. We further evaluated their long-term in vivo performance in a 20-mm sciatic nerve defect rat model. ND/PCL nerve bridges are comparable to autografts in functional, electrophysiological, and morphological sciatic nerve repair. They ameliorate the immune milieu by inducing M1 to M2 macrophage polarization. In addition, they pose no harm to major organs after 4 months of implantation. These findings show the promising roles of ND-based nanotechnology in neuroengineering.

(‐)‐Epigallocatechin gallate‐loaded polycaprolactone scaffolds fabricated using a 3D integrated moulding method alleviate immune stress and induce neurogenesis

“…Melatonin‐loaded polycaprolactone scaffolds alleviated immune insult and improved repair of a 15 mm long sciatic nerve insult by regulating the autophagy signalling pathway . Three‐dimensional nanoceria‐based nerve conduit and nanodiamond channels also contributed to restoration of immune homeostasis by reducing regional oxidative stress and inflammatory reactions in lengthy sciatic nerve defects . Inflammation and oxidative stress are also responsible for radiation‐induced peripheral neuropathy.…”

Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension and Decrease Schwann Cell Expression of Promyelinating Factors

“…Several research groups are developing artificial nerve grafts that contain features that mimic the aligned organization of the native nervous system extracellular matrix (Arslantunali et al, 2014; Abbreviations: BDNF, brain-derived neurotrophic factor; BSA, bovine serum albumin; Cx32, connexin-32; DRG, dorsal root ganglia; GAP43, growth-associated protein 43; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HFP, 1,1,1,3,3,3hexafluoro-2-propanol; HPLC, high-performance liquid chromatography; LCMS, liquid chromatography-mass spectrometry; MBP, myelin basic protein; mRNA, messenger ribonucleic acid; NCAM1, neural cell adhesion molecule 1; Oct6, octamer-binding factor 6; PBS, phosphate-buffered saline; PDGF-BB, plateletderived growth factor-BB; PDMS, polydimethylsiloxane; PLGA, poly(lactic-coglycolic acid); PLLA, poly-L-lactic acid; PMP2, peripheral myelin protein 2; qPCR, quantitative polymerase chain reaction; S1P, sphingosine-1-phosphate; SEM, scanning electron microscopy. Quan et al, 2016;Qian et al, 2018Qian et al, , 2019aHoushyar et al, 2019). Electrospinning can be used to generate a polymer scaffold with highly aligned topography.…”

“…To overcome the limitations of autografts and allografts, artificial nerve grafts have been developed and tested ( Arslantunali et al, 2014 ; López-Cebral et al, 2017 ; Houshyar et al, 2019 ; Kornfeld et al, 2019 ; Qian et al, 2018 , 2019a , b ). Currently, there are nine commercially available biodegradable artificial nerve grafts for peripheral nerve reconstruction; however, these products are only approved for gap distances of 3 cm or less ( Kornfeld et al, 2019 ).…”

High Nanodiamond Content-PCL Composite for Tissue Engineering Scaffolds

“…The fabrication of ND-PCL composites is limited by the fabrication techniques used to manufacture the composites. Using casting and electrospinning, significantly lower ND concentrations of 0.1-6% ND w/v [3,4,21,42] are used to make composites, while herein we are increasing this to 20% ND w/w loading. Here, we use the ND-PCL composite as a base material in a custom-made bioextruder for additive manufacturing.…”