Investigation of auditory neuronal survival and outgrowth using a cochlear implant in an artificial cochlear model

Abstract Cochlear implants (CI) can restore hearing to people suffering from sensorineural hearing loss. The CI uses an array of electrodes inserted in the scala tympani to stimulate the spiral ganglion neurons (SGN), which are located in the bony axis of the inner ear. The spatial distance between the electrodes and the SGN results in spread of excitation and unfocused stimulation. This distance could be bypassed by a neurite outgrowth towards the CI. In order to establish a culture system for the development of novel strategies for CI optimization, a neurite outgrowth chamber (NOC) allowing clinically relevant electrical stimulation paradigms was developed using fused deposition modelling. It was made out of biocompatible UV-curing silicone. The NOC was equipped with a slot to insert the electrode array into a scala tympani compartment whereas SGN isolated from postnatal rats were cultured in a neighbouring region mimicking the Rosenthal’s canal. Sound delivered through loudspeakers playing a radio program was captured by the CI sound processor, positioned outside the NOC, for 17 hours daily during a four-day period. The NOCs were tightly sealed and the electrode array could be positioned in the scala tympani compartment. The experimental setup allowed cell cultivation and the stimulation resulted in a significantly increased neurite length of around 36% while explant area and neurite number did not differ to the negative control (NC). A new in vitro testing system which considers the anatomy of the cochlea and clinic stimulation conditions has been developed and validated. The validation experiments resulted in increased neurite length. This indicates a progress in bridging the anatomical gap between electrode and stimulated neurons.

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In vitro performance of 3D printed PCL−β-TCP degradable spinal fusion cage

Journal of Biomaterials Applications ◽

10.1177/0885328220978492 ◽

2020 ◽

pp. 088532822097849

Author(s):

Xiao Han ◽

Yuan Gao ◽

Yilei Ding ◽

Weijie Wang ◽

Li Liu ◽

...

Keyword(s):

Mechanical Properties ◽

Spinal Fusion ◽

Structural Integrity ◽

Stress Shielding ◽

Fused Deposition Modelling ◽

Spinal Diseases ◽

Fused Deposition ◽

Human Cancellous Bone ◽

Fusion Cage

Spinal fusion cages are commonly used to treat spinal diseases caused by degenerative changes, deformities, and trauma. At present, most of the main clinical spinal fusion cage products are non-degradable and still cause some undesirable side effects, such as the stress shielding phenomenon, interference with postoperative medical imaging, and obvious foreign body sensation in patients. Degradable spinal fusion cages have promising potential with extensive perspectives. The purpose of this study was to fabricate a degradable spinal fusion cage from both polycaprolactone (PCL) and high-proportion beta-tricalcium phosphate (β-TCP), using the highly personalised, accurate, and rapid fused deposition modelling 3 D printing technology. PCL and β-TCP were mixed in three different ratios (60:40, 55:45, and 50:50). Both in vitro degradation and cell experiments proved that all cages with the different PCL:β-TCP ratios met the mechanical properties of human cancellous bone while maintaining their structural integrity. The biological activity of the cages improved with higher amounts of the β-TCP content. This study also showed that a spinal fusion cage with high β-TCP content and suitable mechanical properties can be manufactured using extruding rods and appropriate models, providing a new solution for the design of degradable spinal fusion cages.

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Atrial Natriuretic Peptide Improves Neurite Outgrowth from Spiral Ganglion Neurons In Vitro through a cGMP-Dependent Manner

Neural Plasticity ◽

10.1155/2020/8831735 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Fei Sun ◽

Ke Zhou ◽

Ke-yong Tian ◽

Jie Wang ◽

Jian-hua Qiu ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Neurite Outgrowth ◽

Natriuretic Peptide ◽

Critical Role ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Dependent Manner ◽

Ganglion Neurons ◽

Atrial Natriuretic

The spiral ganglion neurons (SGNs) are the primary afferent neurons in the spiral ganglion (SG), while their degeneration or loss would cause sensorineural hearing loss. As a cardiac-derived hormone, atrial natriuretic peptide (ANP) plays a critical role in cardiovascular homeostasis through binding to its functional receptors (NPR-A and NPR-C). ANP and its receptors are widely expressed in the mammalian nervous system where they could be implicated in the regulation of multiple neural functions. Although previous studies have provided direct evidence for the presence of ANP and its functional receptors in the inner ear, their presence within the cochlear SG and their regulatory roles during auditory neurotransmission and development remain largely unknown. Based on our previous findings, we investigated the expression patterns of ANP and its receptors in the cochlear SG and dissociated SGNs and determined the influence of ANP on neurite outgrowth in vitro by using organotypic SG explants and dissociated SGN cultures from postnatal rats. We have demonstrated that ANP and its receptors are expressed in neurons within the cochlear SG of postnatal rat, while ANP may promote neurite outgrowth of SGNs via the NPR-A/cGMP/PKG pathway in a dose-dependent manner. These results indicate that ANP would play a role in normal neuritogenesis of SGN during cochlear development and represents a potential therapeutic candidate to enhance regeneration and regrowth of SGN neurites.

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Slit1 promotes regenerative neurite outgrowth of adult dorsal root ganglion neurons in vitro via binding to the Robo receptor

Journal of Chemical Neuroanatomy ◽

10.1016/j.jchemneu.2010.02.001 ◽

2010 ◽

Vol 39 (4) ◽

pp. 256-261 ◽

Cited By ~ 12

Author(s):

Hai Ying Zhang ◽

Lin Feng Zheng ◽

Xi Nan Yi ◽

Zhi Bin Chen ◽

Zhong Ping He ◽

...

Keyword(s):

Dorsal Root Ganglion ◽

Neurite Outgrowth ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

Ganglion Neurons

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Atrial Natriuretic Peptide Promotes Neurite Outgrowth and Survival of Cochlear Spiral Ganglion Neurons in vitro Through NPR-A/cGMP/PKG Signaling

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.681421 ◽

2021 ◽

Vol 9 ◽

Author(s):

Fei Sun ◽

Ke Zhou ◽

Ke-yong Tian ◽

Xin-yu Zhang ◽

Wei Liu ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Neurite Outgrowth ◽

Natriuretic Peptide ◽

Neuronal Survival ◽

Spiral Ganglion ◽

Bioactive Molecules ◽

Spiral Ganglion Neurons ◽

Ganglion Neurons ◽

Atrial Natriuretic

Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3’,5’-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptor by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions. Despite former literatures and our reports indicating the existence of ANP and its receptors within the inner ear, particularly in the spiral ganglion, their potential regulatory mechanisms underlying functional properties of auditory neurons are still incompletely understood. Our recently published investigation revealed that ANP could promote the neurite outgrowth of SGNs by activating NPR-A/cGMP/PKG cascade in a dose-dependent manner. In the present research, the influence of ANP and its receptor-mediated downstream signaling pathways on neurite outgrowth, neurite attraction, and neuronal survival of SGNs in vitro was evaluated by employing cultures of organotypic explant and dissociated neuron from postnatal rats. Our data indicated that ANP could support and attract neurite outgrowth of SGNs and possess a high capacity to improve neuronal survival of SGNs against glutamate-induced excitotoxicity by triggering the NPR-A/cGMP/PKG pathway. The neuroregenerative and neuroprotective effects of ANP/NPRA/cGMP/PKG-dependent signaling on SGNs would represent an attractive therapeutic candidate for hearing impairment.

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Preparation and in vitro evaluation of PLA/biphasic calcium phosphate filaments used for fused deposition modelling of scaffolds

Materials Science and Engineering C ◽

10.1016/j.msec.2020.111013 ◽

2020 ◽

Vol 114 ◽

pp. 111013

Author(s):

P. Nevado ◽

A. Lopera ◽

V. Bezzon ◽

M.R. Fulla ◽

J. Palacio ◽

...

Keyword(s):

Calcium Phosphate ◽

Biphasic Calcium Phosphate ◽

Fused Deposition Modelling ◽

In Vitro Evaluation ◽

Fused Deposition

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Inhibition of the c-Jun N-Terminal Kinase Signaling Pathway Influences Neurite Outgrowth of Spiral Ganglion Neurons In Vitro

The Laryngoscope ◽

10.1097/00005537-200211000-00028 ◽

2002 ◽

Vol 112 (11) ◽

pp. 2057-2061 ◽

Cited By ~ 21

Author(s):

Daniel Bodmer ◽

Bertrand Gloddek ◽

Allen F. Ryan ◽

Jochen Huverstuhl ◽

Dominik Brors

Keyword(s):

Neurite Outgrowth ◽

Signaling Pathway ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Kinase Signaling ◽

Ganglion Neurons ◽

Kinase Signaling Pathway

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Direct Cyclodextrin Based Powder Extrusion 3D Printing for One-step Production of the BCS Class II Model Drug Niclosamide

10.21203/rs.3.rs-965993/v1 ◽

2021 ◽

Author(s):

Monica Pistone ◽

Giuseppe Francesco Racaniello ◽

Ilaria Arduino ◽

Valentino Laquintana ◽

Antonio Lopalco ◽

...

Keyword(s):

3D Printing ◽

Hydroxypropyl Methylcellulose ◽

Class Ii ◽

Active Principle ◽

Fused Deposition Modelling ◽

Sustained Drug Release ◽

Pharmaceutical Dosage Forms ◽

Fused Deposition ◽

Bcs Class Ii

Abstract Niclosamide (NCS) is a drug that has been used as an anthelmintic and anti-parasitic active principle for about 40 years. Recently, some studies have highlighted its potential in treating various tumors, allowing a repositioning of this drug. Despite its potential, NCS is a Biopharmaceutical Classification System (BCS) Class II drug, and is consequently characterised by low aqueous solubility, poor dissolution rate and reduced bioavailability, which limits its applicability. In this work, we utilize a very novel technique, Direct Powder Extrusion (DPE) 3D printing, which overcomes the limitations of previously used techniques (Fused Deposition Modelling, FDM) to achieve direct extrusion of pharmaceutical grade powder mixtures consisting of NCS, hydroxypropyl methylcellulose (HPMC, Affinisol 15 LV), hydroxypropyl-b-cyclodextrin (HP-β-CD) and polyethylene glycol (PEG) 6000. For the first time, direct printing of powder blends containing HP-β-CD was explored. For all tablets, in vitro dissolution studies showed sustained drug release over 48 hours, but for tablets containing HP-β-CD, the release was faster. Solid-state characterisation studies showed that during extrusion, the drug lost its crystal structure and was evenly distributed within the polymer matrix. All printed tablets exhibited good mechanical and physical features and guarantee stability of the drug content for up to 3 months. This innovative printing technique has demonstrated the possibility to produce personalised pharmaceutical dosage forms starting directly from powders, avoiding the use of filament used by FDM.

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Rapid prototyping of replica knee implants for in vitro testing

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2016-0122 ◽

2016 ◽

Vol 2 (1) ◽

pp. 553-556 ◽

Cited By ~ 1

Author(s):

Mark Verjans ◽

Malte Asseln ◽

Klaus Radermacher

Keyword(s):

Rapid Prototyping ◽

Implant Design ◽

Fused Deposition Modelling ◽

In Vitro Testing ◽

Knee Biomechanics ◽

Fused Deposition ◽

Kinematic Behaviour ◽

Long Lifetime ◽

Manufacturing Technologies

AbstractThe understanding of the complex biomechanics of the knee is a key for an optimal implant design. To easily investigate the influence of prosthetic designs on knee biomechanics a rapid prototyping workflow for knee implants has been developed and evaluated. Therefore, different manufacturing technologies and post-treatment methods have been examined and overall seven different replica knee implants were manufactured. For evaluation, the manufacturing properties such as surface accuracy and roughness were determined and kinematic behaviour was investigated in a novel knee testing rig. It was carried out that PolyJet-Modelling with a sanded surface resulted in changed kinematic patterns compared to a usual CoCr-UHMWPE implant. However, fused deposition modelling using ABS and subsequent surface smoothening with acetone vapor showed the lowest roughness of the manufactured implants and only minor kinematic differences. For this reason this method constitutes a promising approach towards an optimal implant design for improved patient-satisfaction and long lifetime of the implant. Finally the workflow is not only limited to the knee.

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