scholarly journals Microdevice for directional axodendritic connectivity between micro 3D neuronal cultures

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yixuan Ming ◽  
Md Joynal Abedin ◽  
Svetlana Tatic-Lucic ◽  
Yevgeny Berdichevsky

AbstractNeuronal cultures are widely used in neuroscience research. However, the randomness of circuits in conventional cultures prevents accurate in vitro modeling of cortical development and of the pathogenesis of neurological and psychiatric disorders. A basic feature of cortical circuits that is not captured in standard cultures of dissociated cortical cells is directional connectivity. In this work, a polydimethylsiloxane (PDMS)-based device that achieves directional connectivity between micro 3D cultures is demonstrated. The device consists of through-holes for micro three-dimensional (μ3D) clusters of cortical cells connected by microtrenches for axon and dendrite guidance. The design of the trenches relies in part on the concept of axonal edge guidance, as well as on the novel concept of specific dendrite targeting. This replicates dominant excitatory connectivity in the cortex, enables the guidance of the axon after it forms a synapse in passing (an “en passant” synapse), and ensures that directional selectivity is preserved over the lifetime of the culture. The directionality of connections was verified morphologically and functionally. Connections were dependent on glutamatergic synapses. The design of this device has the potential to serve as a building block for the reconstruction of more complex cortical circuits in vitro.

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2273
Author(s):  
Wan-Ying Huang ◽  
Norichika Hashimoto ◽  
Ryuhei Kitai ◽  
Shin-ichiro Suye ◽  
Satoshi Fujita

The occasional malignant transformation of intracranial epidermoid cysts into squamous cell carcinomas remains poorly understood; the development of an in vitro cyst model is urgently needed. For this purpose, we designed a hollow nanofiber sphere, the “nanofiber-mâché ball.” This hollow structure was fabricated by electrospinning nanofiber onto alginate hydrogel beads followed by dissolving the beads. A ball with approximately 230 mm3 inner volume provided a fibrous geometry mimicking the topography of the extracellular matrix. Two ducts located on opposite sides provided a route to exchange nutrients and waste. This resulted in a concentration gradient that induced oriented migration, in which seeded cells adhered randomly to the inner surface, formed a highly oriented structure, and then secreted a dense web of collagen fibrils. Circumferentially aligned fibers on the internal interface between the duct and hollow ball inhibited cells from migrating out of the interior, similar to a fish bottle trap. This structure helped to form an adepithelial layer on the inner surface. The novel nanofiber-mâché technique, using a millimeter-sized hollow fibrous scaffold, is excellently suited to investigating cyst physiology.


2019 ◽  
Author(s):  
Liam M. Rooney ◽  
Lisa S. Kölln ◽  
Ross Scrimgeour ◽  
William B. Amos ◽  
Paul A. Hoskisson ◽  
...  

The Delta-proteobacterium, Myxococcus xanthus, has been used as a model for bacterial motility and to provide insights of bacterial swarming behaviours. Fluorescence microscopy techniques have shown that various mechanisms are involved in gliding motility, but these have almost entirely been limited to 2D studies and there is currently no understanding of gliding motility in a 3D context. We present here the first use of confocal interference reflection microscopy (IRM) to study gliding bacteria, and we reveal aperiodic oscillatory behaviour with changes in the position of the basal membrane relative to the coverglass on the order of 90 nm in vitro. Firstly, we use a model plano-convex lens specimen to show how topological information can be obtained from the wavelength-dependent interference pattern in IRM. We then use IRM to observe gliding M. xanthus and show that cells undergo previously unobserved changes in their height as they glide. We compare the wild-type with mutants of reduced motility, which also exhibit the same changes in adhesion profile during gliding. We find that the general gliding behaviour is independent of the proton motive force-generating complex, AglRQS, and suggest that the novel behaviour we present here may be a result of recoil and force transmission along the length of the cell body following firing of the Type IV pili.


Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2203 ◽  
Author(s):  
JunJie Yu ◽  
SuJeong Lee ◽  
Sunkyung Choi ◽  
Kee K. Kim ◽  
Bokyeong Ryu ◽  
...  

Osteochondral defects, including damage to both the articular cartilage and the subchondral bone, are challenging to repair. Although many technological advancements have been made in recent years, there are technical difficulties in the engineering of cartilage and bone layers, simultaneously. Moreover, there is a great need for a valuable in vitro platform enabling the assessment of osteochondral tissues to reduce pre-operative risk. Three-dimensional (3D) bioprinting systems may be a promising approach for fabricating human tissues and organs. Here, we aimed to develop a polycaprolactone (PCL)/alginate bipartite hybrid scaffold using a multihead 3D bioprinting system. The hybrid scaffold was composed of PCL, which could improve the mechanical properties of the construct, and alginate, encapsulating progenitor cells that could differentiate into cartilage and bone. To differentiate the bipartite hybrid scaffold into osteochondral tissue, a polydimethylsiloxane coculture system for osteochondral tissue (PCSOT) was designed and developed. Based on evaluation of the biological performance of the novel hybrid scaffold, the PCL/alginate bipartite scaffold was successfully fabricated; importantly, our findings suggest that this PCSOT system may be applicable as an in vitro platform for osteochondral tissue engineering.


Perfusion ◽  
2002 ◽  
Vol 17 (2) ◽  
pp. 153-156 ◽  
Author(s):  
Anja Gerdes ◽  
Thorsten Hanke ◽  
Hans-H Sievers

Background: Prevention of intraoperative plaque dislodgement in patients with atherosclerotic ascending aorta by development of innovative aortic cannula designs gains growing interest in cardiac surgery. To increase knowledge about the hydrodynamics of the innovative Embol-X™ cannula, which includes an intra-aortic filter device targeting at atheromatous emboli capture, was the aim of the present study. Methods: Pressure gradients and back pressures of the Embol-X™ cannula were measured at varying flow rates in a mock circulation and compared with two commonly used single-stream cannulae. Results: At a flow rate of 5.5 l/min, pressure gradients across the Argyle™ and the RMI cannulae were 48% and 62% and back pressures 25% and 47% lower than the corresponding values across the Embol-X™ cannula. Conclusions: The novel concept of integrating a filter device may provide clinical advantages concerning neurologic outcome. Further in vivo studies seem to be desirable to obtain more information concerning the clinical effects of the Embol-X™ cannula hydrodynamics.


Open Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 180177 ◽  
Author(s):  
Yi-Ying Wu ◽  
Feng-Lan Chiu ◽  
Chan-Shien Yeh ◽  
Hung-Chih Kuo

Adult-onset neurodegenerative diseases are among the most difficult human health conditions to model for drug development. Most genetic or toxin-induced cell and animal models cannot faithfully recapitulate pathology in disease-relevant cells, making it excessively challenging to explore the potential mechanisms underlying sporadic disease. Patient-derived induced pluripotent stem cells (iPSCs) can be differentiated into disease-relevant neurons, providing an unparalleled platform for in vitro modelling and development of therapeutic strategies. Here, we review recent progress in generating Alzheimer's, Parkinson's and Huntington's disease models from patient-derived iPSCs. We also describe novel discoveries of pathological mechanisms and drug evaluations that have used these patient iPSC-derived neuronal models. Additionally, current human iPSC technology allows researchers to model diseases with 3D brain organoids, which are more representative of tissue architecture than traditional neuronal cultures. We discuss remaining challenges and emerging opportunities for the use of three-dimensional brain organoids in modelling brain development and neurodegeneration.


2004 ◽  
Vol 48 (5) ◽  
pp. 1495-1502 ◽  
Author(s):  
Irina V. Alymova ◽  
Garry Taylor ◽  
Toru Takimoto ◽  
Tsu-Hsing Lin ◽  
Pooran Chand ◽  
...  

ABSTRACT Human parainfluenza viruses are important respiratory tract pathogens, especially of children. However, no vaccines or specific therapies for infections caused by these viruses are currently available. In the present study we characterized the efficacy of the novel parainfluenza virus inhibitors BCX 2798 and BCX 2855, which were designed based on the three-dimensional structure of the hemagglutinin-neuraminidase (HN) protein. The compounds were highly effective in inhibiting hemagglutinin (HA) and neuraminidase (NA) activities and the growth of hPIV-1, hPIV-2, and hPIV-3 in LLC-MK2 cells. The concentrations required to reduce the activity to 50% of that of a control ranged from 0.1 to 6.0 μM in HA inhibition assays and from 0.02 to 20 μM in NA inhibition assays. The concentrations required to inhibit virus replication to 50% of the level of the control ranged from 0.7 to 11.5 μM. BCX 2798 and BCX 2855 were inactive against influenza virus HA and NA and bacterial NA. In mice infected with a recombinant Sendai virus whose HN gene was replaced with that of hPIV-1 [rSV(hHN)], intranasal administration of BCX 2798 (10 mg/kg per day) and of BCX 2855 (50 mg/kg per day) 4 h before the start of infection resulted in a significant reduction in titers of virus in the lungs and protection from death. Treatment beginning 24 h after the start of infection did not prevent death. Together, our results indicate that BCX 2798 and BCX 2855 are effective inhibitors of parainfluenza virus HN and may limit parainfluenza virus infections in humans.


2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Martina Brofiga ◽  
Marietta Pisano ◽  
Mariateresa Tedesco ◽  
Francesca Callegari ◽  
Paolo Massobrio

In this work, we present a novel experimental platform to build in vitro interconnected (i.e., modular) heterogeneous (e.g., cortical-hippocampal) and three-dimensional (3D) neuronal cultures plated on Micro-Electrode Arrays (MEAs) to extracellularly record the electrophysiological activity continuously.


Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 2047 ◽  
Author(s):  
Yunpeng Bai ◽  
Takahiro Kanno ◽  
Hiroto Tatsumi ◽  
Kenichi Miyamoto ◽  
Jingjing Sha ◽  
...  

This study evaluated the feasibility of a novel three-dimensional (3D) porous composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-d/l-lactide (PDLLA) (3D-HA/PDLLA) for the bony regenerative biomaterial in maxillofacial surgery, focusing on cellular activities and osteoconductivity properties in vitro and in vivo. In the in vitro study, we assessed the proliferation and ingrowth of preosteoblastic cells (MC3T3-E1 cells) in 3D-HA/PDLLA biomaterials using 3D cell culture, and the results indicated enhanced bioactive proliferation. After osteogenic differentiation of those cells on 3D-HA/PDLLA, the osteogenesis marker genes runt-related transcription factor-2 (Runx2), and Sp7 (Osterix) were upregulated. For the in vivo study, we evaluated the utility of 3D-HA/PDLLA biomaterials compared to the conventional bone substitute of beta-tricalcium phosphate (β-TCP) in rats with critical mandibular bony defects. The implantation of 3D-HA/PDLLA biomaterials resulted in enhanced bone regeneration, by inducing high osteoconductivity as well as higher β-TCP levels. Our study thus showed that the novel composite, 3D-HA/PDLLA, is an excellent bioactive/bioresorbable biomaterial for use as a cellular scaffold, both in vitro and in vivo, and has utility in bone regenerative therapy, such as for patients with irregular maxillofacial bone defects.


2021 ◽  
Vol 9 (3) ◽  
pp. 671-678
Author(s):  
Amna Aziz ◽  
Aniqa Rashid ◽  
Aqsa Aslam ◽  
Iqra Nazish ◽  
Khadija Majeed

Purpose of the study: This study contextualizes within the border of psychoanalytical perspective specifically focusing on Freud's theory of personality and Lacan’s module of the psyche to evaluate an artist’s mental state that how his/her mental state fluctuates. Methodology: Bali Jatti is taken as an exemplary character to project the reality of being an artist. This analysis presents her three-dimensional world, real, theatrical, and psychological, to represent the challenges she faces as she opts to embrace the life of folk theatre. It explores her psychological life and the chaos in which she spends the rest of her life. It probes into social taboos and stigmas that are associated with her life that makes her a stereotypical icon. Main Findings: This research concludes that the psychological world of folk theatre Bali is under the hegemonic supremacy of the other two worlds, real and theatrical. This diligent inquiry leads the reader through a steady stream of events of Bali's life which is taken as an exemplary character to project the reality of being an artist. Applications of this study: This study provides guidelines to academia and probes into an exploration of the novel concept of Pakistan folk theatre and its artist's three-dimensional world. Novelty/Originality of this study: From a theoretical perspective, this study provides important insights into literature by exploring the most demanding skills in folk theatre artists and their three-dimensional world that formulates their destiny and takes their journey of life from glory to demise.


Author(s):  
Qing Zhang

The microenvironment in which cells reside in vivo dictates their biological and mechanical functioning is associated with morphogenetic and regenerative processes and may find implications in regenerative medicine and tissue engineering. The development of nano- and micro-fabricated technologies, three-dimensional (3D) printing technique, and biomimetic medical materials have enabled researchers to prepare novel advanced substrates mimicking the in vivo microenvironment. Most of the novel morphologies and behaviors of cells, including contact guidance and cell bridges which are observed in vivo but are not perceived in the traditional two-dimensional (2D) culture system, emerged on those novel substrates. Using cell bridges, cell can span over the surface of substrates to maintain mechanical stability and integrity of tissue, as observed in physiological processes, such as wound healing, regeneration and development. Compared to contact guidance, which has received increased attention and is investigated extensively, studies on cell bridges remain scarce. Therefore, in this mini-review, we have comprehensively summarized and classified different kinds of cell bridges formed on various substrates and highlighted possible biophysical mechanisms underlying cell bridge formation for their possible implication in the fields of tissue engineering and regenerative medicine.


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