Engineering‐Aligned 3D Neural Circuit in Microfluidic Device

Bang, Seokyoung; Na, Sangcheol; Jang, Jyongsik; Kim, Jinhyun; Jeon, Noo Li

doi:10.1002/adhm.201500397

Cited by 69 publications

(87 citation statements)

References 29 publications

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“…Nevertheless, each tissue and organ is unique and has very welldefined functions, and therefore, the challenge in recreating such living environments while considering a particular fabrication technology is overwhelming. Although microfluidic systems still enable quite simple models of the enormous complexity of human tissues and organs, they have contributed to significant developments in brain, 53 kidney, 54 heart, 55,56 or neural 57 modeling, providing more complex systems with well-defined architectures mimicking more closely cellular environments of a physiological niche to understand biological mechanisms.…”

Section: New Trends and Directions-a Year In Review 215mentioning

confidence: 99%

“…56 The feasibility of a 3D model with axonal properties resembling structural features of brain tissue was demonstrated by the establishment of a 3D neural network in a microfluidics chip under a continuous flow. 57 In the neural circuit fabricated, the ECM fibers aligned due to the influence of the hydrostatic pressure over the crosslinking density patterns of the hydrogels, the growth of cortical neurons, and the formation of axon bundles.…”

Section: New Trends and Directions-a Year In Review 215mentioning

confidence: 99%

“…57 In the neural circuit fabricated, the ECM fibers aligned due to the influence of the hydrostatic pressure over the crosslinking density patterns of the hydrogels, the growth of cortical neurons, and the formation of axon bundles.…”

mentioning

confidence: 99%

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Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review

Gomes

Rodrigues

Domingues

et al. 2017

Tissue Engineering Part B: Reviews

152

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Tissue engineering (TE) is continuously evolving assimilating inputs from adjacent scientific areas and their technological advances, including nanotechnology developments that have been spawning the range of available options for the precise manipulation and control of cells and cellular environments. Simultaneously, with the maturation of the field, TE has a growing and marked impact in other fields, such as cancer and other diseases research, enabling tri-dimensional (3D) tumor/tissue models of increased complexity that more closely resemble living tissue dynamics, playing a decisive role in the development of new and improved therapies. Nevertheless, TE is still struggling with translational issues. On this matter, the advent of personalized and precision medicine has opened new perspectives, particularly with the striking evolutions enabled by 3D bioprinting technologies. Based on a modified methodology grounded in the past years' approach, we have identified and reviewed some of the most high-impact publications on the topics that are revolutionizing TE and helping to define the future directions of the field, namely: (1) New trends in TE: Personalized/precision regenerative medicine and 3D bioprinting, (2) Contributions of TE to other fields: microfabricated tissueengineered 3D models for cancer and other diseases research, and (3) Diagnostic and theranostic tools: monitoring and real-time control of TE systems.Keywords: 3D bioprinting, 3D disease models, nanotechnology, precision regenerative medicine, theranostic toolsThe Aim, Scope, and Methods of This Review S ince its origin, tissue engineering (TE) holds the promise of revolutionizing healthcare by providing artificially developed tissues and organs substitutes on demand. More recently, TE has expanded into different biomedical areas to feedback research and clinical needs, widening the range not only of possible successful therapies but also of diagnostic/screening tools. Considering the growing number of publications related with TE and approaching different scientific domains, such as cancer science or pharmaceutics research, the potential complementary role of the field in a multitude of clinical areas and therapies in the years to come is evident.Our review attempts to cover some of the most exciting research contributing to both regenerative medicine and in vitro research applications of engineered tissues, along with the novel technological approaches that are advancing the field. This is the fifth review of the kind in TE. The previous four articles [1][2][3][4] helped to establish the methodology adopted for selecting the areas of focus and the contributions to highlight. As in previous years, we started by searching the ISI Web of Knowledge database for articles in ''tissue engineering'' and ''regenerative medicine'' published during the period of September 2015 through December 2016, thus using a 3-month overlap with the previous review to not miss impactful articles in areas not addressed earlier.Similar to previous years, we also consid...

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Section: New Trends and Directions-a Year In Review 215mentioning

confidence: 99%

Section: New Trends and Directions-a Year In Review 215mentioning

confidence: 99%

See 1 more Smart Citation

Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review

Gomes

Rodrigues

Domingues

et al. 2017

Tissue Engineering Part B: Reviews

152

View full text Add to dashboard Cite

show abstract

“…Midori Kato-Negishi, Hiroaki Onoe, Akane Ito, and Shoji Takeuchi* DOI: 10.1002/adhm.201700143 guidance [12,26] have also been developed as alternative means of controlling cell patterning with high cell density and/or aligned nerve fibers. However, coculturing different types of neural tissues is still difficult because culture conditions such as medium, growth factors, and extracellular matrix (ECM) differ according to the type of neural tissues.…”

Section: Rod-shaped Neural Units For Aligned 3d Neural Network Connecmentioning

confidence: 99%

Rod‐Shaped Neural Units for Aligned 3D Neural Network Connection

Kato-Negishi

Onoe

Ito

et al. 2017

Adv Healthcare Materials

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COMMUNICATION (1 of 7)© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Rod-Shaped Neural Units for Aligned 3D Neural Network ConnectionMidori Kato-Negishi, Hiroaki Onoe, Akane Ito, and Shoji Takeuchi* DOI: 10.1002/adhm.201700143 guidance [12,26] have also been developed as alternative means of controlling cell patterning with high cell density and/or aligned nerve fibers. However, coculturing different types of neural tissues is still difficult because culture conditions such as medium, growth factors, and extracellular matrix (ECM) differ according to the type of neural tissues. [27][28][29][30][31][32][33] Neurons also have the characteristic of axon overproduction and, consequently, axons extend over a wide area during early development. [34][35][36] Therefore, selective connectivity between specific, spatially separated neural tissues is technically difficult.This paper proposes neural tissue units with aligned nerve fibers, called "rodshaped neural units," that can connect spatially separate neural regions (Figure 1). To fabricate these units, we employ a meterlong microfiber-shaped neural tissue [22,23] as starting material, in which stem-cell-derived or primary neural cells are encapsulated and aligned within an alginate tubular hydrogel. This tissue is cut into millimeter-sized sections and, after further cell culturing, both edges of the sections bulge out and form spherical ends (Figure 1b). The proposed rod-shaped neural units have the following characteristics: (1) nerve fibers are aligned in the longitudinal direction of the rod, (2) each unit has an insulated region covered with a thin alginate hydrogel layer to prevent the encapsulated neural tissues from connecting to surrounding cells within the regions, and (3) the edges of the unit are connectable, with the spherical ends functioning as glue to connect with other neural tissues or units. In this study, we designed and fabricated the rod-shaped neural units and characterized their connectivity in terms of neuronal morphologies and network formation. In addition, we constructed a neural network from different types of neural tissues in different culture conditions, with connections to specific, spatially neural regions. Therefore, our neural units assembly can coculture different types of neural tissues with aligned nerve fibers that recapitulate the topological complexity of in vivo neural networks with high cell density and cell population.Rod-shaped neural units were prepared by cutting microfibershaped neural tissues, as reported previously. [22,23,37,38] We used three types of neural cells to fabricate microfiber-shaped neural tissues: primary mouse neural stem cells (mNSCs) dissected from the midbrain of mice (mNSC units), primary cortical cells (cortical units), and primary hippocampal cells (hippocampal units). To prepare the rod-shaped neural units in an accurate and reproducible manner, we developed a fiber-cutting device that can fix the microfiber-shaped neural tissues in a culture In the brain, 3D neural networks such as the hippoc...

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“…Similarly, creation of neural circuit models using different microdevices has been investigated. For example creation of a lower motor neuron–neuromuscular junction circuit using microgrooves 143 , a 3D neural circuit using a microdevice consisting of ECM components and micropillar arrays 144 , and acompartmentalized microsystem 145 have all been reported. In regard to application of stem cells and microfabrication devices for this purpose, one example reported a microfabricated compartmentalized chamber with proteins micropatterned on the surfaces for investigating the effects of fibroblast growth factor receptor (FGFR) signaling on guidance and outgrowth of ESCs-derived axons, and creation of functional neural circuits 146 .…”

Section: Stem Cells In Microfluidic-based Neural Tissue Engineeringmentioning

confidence: 99%

Microfluidic systems for stem cell-based neural tissue engineering

et al. 2016

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Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a “brain-on-a-chip”. In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

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Engineering‐Aligned 3D Neural Circuit in Microfluidic Device

Cited by 69 publications

References 29 publications

Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review

Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review

Rod‐Shaped Neural Units for Aligned 3D Neural Network Connection

Microfluidic systems for stem cell-based neural tissue engineering

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