scholarly journals Extrusion-Printing of Multi-Channeled Two-Component Hydrogel Constructs from Gelatinous Peptides and Anhydride-Containing Oligomers

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 370
Author(s):  
Jan Krieghoff ◽  
Johannes Rost ◽  
Caroline Kohn-Polster ◽  
Benno Müller ◽  
Andreas Koenig ◽  
...  
Keyword(s):  
3D Printing ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Organic N ◽  
Cross Linking ◽  
Two Component ◽  
The Cross ◽  
Small Channels

The performance of artificial nerve guidance conduits (NGC) in peripheral nerve regeneration can be improved by providing structures with multiple small channels instead of a single wide lumen. 3D-printing is a strategy to access such multi-channeled structures in a defined and reproducible way. This study explores extrusion-based 3D-printing of two-component hydrogels from a single cartridge printhead into multi-channeled structures under aseptic conditions. The gels are based on a platform of synthetic, anhydride-containing oligomers for cross-linking of gelatinous peptides. Stable constructs with continuous small channels and a variety of footprints and sizes were successfully generated from formulations containing either an organic or inorganic gelation base. The adjustability of the system was investigated by varying the cross-linking oligomer and substituting the gelation bases controlling the cross-linking kinetics. Formulations with organic N‑methyl-piperidin-3-ol and inorganic K2HPO4 yielded hydrogels with comparable properties after manual processing and extrusion-based 3D-printing. The slower reaction kinetics of formulations with K2HPO4 can be beneficial for extending the time frame for printing. The two-component hydrogels displayed both slow hydrolytic and activity-dependent enzymatic degradability. Together with satisfying in vitro cell proliferation data, these results indicate the suitability of our cross-linked hydrogels as multi-channeled NGC for enhanced peripheral nerve regeneration.

scholarly journals Translational strategies in peripheral neuroinflammation and neurovascular repair

2012 ◽  
Vol 3 (4) ◽  
Author(s):  
Eroboghene Ubogu
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Axonal Degeneration ◽  
Peripheral Nerve Regeneration ◽  
Treatment Strategies ◽  
Normal Function ◽  
New Drugs ◽  
Immune Mediated ◽  
Current Therapies

AbstractCurrent therapies for immune-mediated inflammatory disorders in peripheral nerves are non-specific, and partly efficacious. Peripheral nerve regeneration following axonal degeneration or injury is suboptimal, with current therapies focused on modulating the underlying etiology and treating the consequences, such as neuropathic pain and weakness. Despite significant advances in understanding mechanisms of peripheral nerve inflammation, as well as axonal degeneration and regeneration, there has been limited translation into effective new drugs for these disorders. A major limitation in the field has been the unavailability of reliable disease models or research tools that mimic some key essential features of these human conditions. A relatively overlooked aspect of peripheral nerve regeneration has been neurovascular repair required to restore the homeostatic microenvironment necessary for normal function. Using Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as examples of human acute and chronic immune-mediated peripheral neuroinflammatory disorders respectively, we have performed detailed studies in representative mouse models to demonstrate essential features of the human disorders. These models are important tools to develop and test treatment strategies using realistic outcomes measures applicable to affected patients. In vitro models of the human blood-nerve barrier using endothelial cells derived by endoneurial microvessels provide insights into pro-inflammatory leukocyte-endothelial cell interactions relevant to peripheral neuroinflammation, as well as potential mediators and signaling pathways required for vascular proliferation, angiogenesis, remodeling and tight junction specialization necessary to restore peripheral nerve function following injury. This review discusses some of the progress being made in translational peripheral neurobiology and some future

Producing Neurospheroids and Hydrogels to Create a Three-dimensional in Vitro Model for the Use of Conduits in Peripheral Nerve Regeneration

Neurosurgery ◽  
2019 ◽  
Vol 84 (5) ◽  
pp. E272-E272
Author(s):  
Devyani Shete ◽  
Aran Batth ◽  
Aditi Nijhawan ◽  
Jaffer Choudhary ◽  
Ian Thompson
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
3D Structure ◽  
Three Dimensional ◽  
Negative Control ◽  
Cellular Growth ◽  
Live Cells

Abstract INTRODUCTION Peripheral nerve regeneration is a complex challenge that requires suitable nerve guidance systems to bridge the severed ends of 2 nerves back together. Current polymeric conduits on the market provide good cellular growth but are limited by the length of gap defect they can repair, and complete functional recovery is rare. This project focused on creating a three-dimensional (3D) in Vitro spheroidal sprouting assay for peripheral nerve regeneration, as well as producing and testing different polymeric hydrogels as potential scaffold materials for the conduit. METHODS Different concentrations of chitosan, methylcellulose (MC) and sodium alginate were produced, as well as blends of these materials. These hydrogels were seeded with 3D neurospheroids, along with NG108-15 (neuronal) cells and Schwann cells to test their biocompatibility. RESULTS MTT assays showed the mean absorbance of chitosan gels with NG108-15 cells at 24 hr (P < .001) and 72 hr (P > .05) was similar/slightly higher than the negative control. Live-Dead data showed 93.4% of live cells at DIV7 on MC: Ch blends, compared to 72% with chitosan alone. CONCLUSION Overall, both chitosan and MC were nontoxic and biocompatible with NG108-15 and Schwann cells. Blending chitosan with MC improved its chemical and physical properties. The cells formed spheroids that well on a gel; this pseudo-3D structure is excellent for research purposes compared to 2D as it mimics the body's internal environment.

Effect of Arecoline on Regeneration of Injured Peripheral Nerves

2013 ◽  
Vol 41 (04) ◽  
pp. 865-885 ◽  
Author(s):  
Sheng-Chi Lee ◽  
Chin-Chuan Tsai ◽  
Chun-Hsu Yao ◽  
Yuan-Man Hsu ◽  
Yueh-Sheng Chen ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
In Vitro Study ◽  
Control Group ◽  
Neural Cells ◽  
In Vivo Evaluation

The present study provides in vitro and in vivo evaluation of arecoline on peripheral nerve regeneration. In the in vitro study, we found that arecoline at 50 μg/ml could significantly promote the survival and outgrowth of cultured Schwann cells as compared to the controls treated with culture medium only. In the in vivo study, we evaluated peripheral nerve regeneration across a 10-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve chamber filled with the arecoline solution. In the control group, the chambers were filled with normal saline only. At the end of the fourth week, morphometric data revealed that the arecoline-treated group at 5 μg/ml significantly increased the number and the density of myelinated axons as compared to the controls. Immunohistochemical staining in the arecoline-treated animals at 5 μg/ml also showed their neural cells in the L4 and L5 dorsal root ganglia ipsilateral to the injury were strongly retrograde-labeled with fluorogold and lamina I–II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled compared with the controls. In addition, we found that the number of macrophages recruited in the distal sciatic nerve was increased as the concentration of arecoline was increased. Electrophysiological measurements showed the arecoline-treated groups at 5 and 50 μg/ml had a relatively larger nerve conductive velocity of the evoked muscle action potentials compared to the controls. These results indicate that arecoline could stimulate local inflammatory conditions, improving the recovery of a severe peripheral nerve injury.

scholarly journals Fibroblast Growth Factor 13 Facilitates Peripheral Nerve Regeneration through Maintaining Microtubule Stability

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Rui Li ◽  
Xuetao Tao ◽  
Minghong Huang ◽  
Yan Peng ◽  
Jiahong Liang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Fibroblast Growth Factor ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Fibroblast Growth ◽  
Promising Alternative ◽  
Microtubule Stability

Peripheral nerve injury (PNI), resulting in the impairment of myelin sheaths and axons, seriously affects the transmission of sensory or motor nerves. Growth factors (GFs) provide a biological microenvironment for supporting nerve regrowth and have become a promising alternative for repairing PNI. As one number of intracellular growth factor family, fibroblast growth factor 13 (FGF13) was regard as a microtubule-stabilizing protein for regulating cytoskeletal plasticity and neuronal polarization. However, the therapeutic efficiency and underlying mechanism of FGF13 for treating PNI remained unknown. Here, the application of lentivirus that overexpressed FGF13 was delivered directly to the lesion site of transverse sciatic nerve for promoting peripheral nerve regeneration. Through behavioral analysis and histological and ultrastructure examinations, we found that FGF13 not only facilitated motor and sense functional recovery but also enhanced axon elongation and remyelination. Furthermore, pretreatment with FGF13 also promoted Schwann cell (SC) viability and upregulated the expression cellular microtubule-associated proteins in vitro PNI model. These data indicated FGF13 therapeutic effect was closely related to maintain cellular microtubule stability. Thus, this work provides the evident that FGF13-medicated microtubule stability is necessary for promoting peripheral nerve repair following PNI, highlighting the potential therapeutic value of FGF13 on ameliorating injured nerve recovery.

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