An automated microfluidic platform integrating functional vascularized organoids-on-chip

The development of vascular networks on-chip is crucial for the long-term culture of three-dimensional cell aggregates such as organoids, spheroids, tumoroids, and tissue explants. Despite the rapid advancement of microvascular network systems and organoid technology, vascularizing organoids-on-chips remains a challenge in tissue engineering. Moreover, most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical settings to operate. Considering these constraints, we developed an innovative platform to establish and monitor the formation of endothelial networks around model spheroids of mesenchymal and endothelial cells as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 15 days on-chip. Importantly, these networks were functional, demonstrating intravascular perfusion within the spheroids or vascular organoids connected to neighbouring endothelial beds. This microphysiological system thus represents a viable organ-on-chip model to vascularize biological tissues and should allow to establish perfusion into organoids using advanced microfluidics.

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Multi-Organs-on-Chips: Towards Long-Term Biomedical Investigations

Molecules ◽

10.3390/molecules24040675 ◽

2019 ◽

Vol 24 (4) ◽

pp. 675 ◽

Cited By ~ 22

Author(s):

Yi Zhao ◽

Ranjith Kankala ◽

Shi-Bin Wang ◽

Ai-Zheng Chen

Keyword(s):

Real Time ◽

Three Dimensional ◽

Drug Efficacy ◽

Dynamic Responses ◽

Physical Parameters ◽

Real Time Monitoring ◽

Multiple Organs ◽

On Chip

With advantageous features such as minimizing the cost, time, and sample size requirements, organ-on-a-chip (OOC) systems have garnered enormous interest from researchers for their ability for real-time monitoring of physical parameters by mimicking the in vivo microenvironment and the precise responses of xenobiotics, i.e., drug efficacy and toxicity over conventional two-dimensional (2D) and three-dimensional (3D) cell cultures, as well as animal models. Recent advancements of OOC systems have evidenced the fabrication of ‘multi-organ-on-chip’ (MOC) models, which connect separated organ chambers together to resemble an ideal pharmacokinetic and pharmacodynamic (PK-PD) model for monitoring the complex interactions between multiple organs and the resultant dynamic responses of multiple organs to pharmaceutical compounds. Numerous varieties of MOC systems have been proposed, mainly focusing on the construction of these multi-organ models, while there are only few studies on how to realize continual, automated, and stable testing, which still remains a significant challenge in the development process of MOCs. Herein, this review emphasizes the recent advancements in realizing long-term testing of MOCs to promote their capability for real-time monitoring of multi-organ interactions and chronic cellular reactions more accurately and steadily over the available chip models. Efforts in this field are still ongoing for better performance in the assessment of preclinical attributes for a new chemical entity. Further, we give a brief overview on the various biomedical applications of long-term testing in MOCs, including several proposed applications and their potential utilization in the future. Finally, we summarize with perspectives.

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High-resolution three-dimensional probes of biomaterials and their interfaces

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2011.0253 ◽

2012 ◽

Vol 370 (1963) ◽

pp. 1337-1351 ◽

Cited By ~ 19

Author(s):

Kathryn Grandfield ◽

Anders Palmquist ◽

Håkan Engqvist

Keyword(s):

High Resolution ◽

Electron Tomography ◽

Three Dimensional ◽

Controlled Drug Release ◽

Biological Tissues ◽

Dimensional Structure ◽

Bone Interface ◽

Biomaterial Interfaces ◽

Titania Coating

Interfacial relationships between biomaterials and tissues strongly influence the success of implant materials and their long-term functionality. Owing to the inhomogeneity of biological tissues at an interface, in particular bone tissue, two-dimensional images often lack detail on the interfacial morphological complexity. Furthermore, the increasing use of nanotechnology in the design and production of biomaterials demands characterization techniques on a similar length scale. Electron tomography (ET) can meet these challenges by enabling high-resolution three-dimensional imaging of biomaterial interfaces. In this article, we review the fundamentals of ET and highlight its recent applications in probing the three-dimensional structure of bioceramics and their interfaces, with particular focus on the hydroxyapatite–bone interface, titanium dioxide–bone interface and a mesoporous titania coating for controlled drug release.

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Three-Dimensional Networks-on-Chip Architectures

Embedded Multi-Core Systems - Networks-on-Chips ◽

10.1201/9781420079791.ch1 ◽

2009 ◽

pp. 1-27 ◽

Cited By ~ 6

Author(s):

Kostas Siozios ◽

Alexandros Bartzas ◽

Dimitrios Soudris

Keyword(s):

Three Dimensional ◽

Networks On Chip ◽

On Chip

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Microribbons composed of directionally self-assembled nanoflakes as highly stretchable ionic neural electrodes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2003079117 ◽

2020 ◽

Vol 117 (26) ◽

pp. 14667-14675 ◽

Cited By ~ 2

Author(s):

Mingchao Zhang ◽

Rui Guo ◽

Ke Chen ◽

Yiliang Wang ◽

Jiali Niu ◽

...

Keyword(s):

Self Assembly ◽

Structural Variation ◽

Three Dimensional ◽

Biological Tissues ◽

Superior Performance ◽

Ionic Conductors ◽

Structural Variations ◽

Neural Electrodes ◽

Self Assembled

Many natural materials possess built-in structural variation, endowing them with superior performance. However, it is challenging to realize programmable structural variation in self-assembled synthetic materials since self-assembly processes usually generate uniform and ordered structures. Here, we report the formation of asymmetric microribbons composed of directionally self-assembled two-dimensional nanoflakes in a polymeric matrix during three-dimensional direct-ink printing. The printed ribbons with embedded structural variations show site-specific variance in their mechanical properties. Remarkably, the ribbons can spontaneously transform into ultrastretchable springs with controllable helical architecture upon stimulation. Such springs also exhibit superior nanoscale transport behavior as nanofluidic ionic conductors under even ultralarge tensile strains (>1,000%). Furthermore, to show possible real-world uses of such materials, we demonstrate in vivo neural recording and stimulation using such springs in a bullfrog animal model. Thus, such springs can be used as neural electrodes compatible with soft and dynamic biological tissues.

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Networks-on-Chip in a Three-Dimensional Environment: A Performance Evaluation

IEEE Transactions on Computers ◽

10.1109/tc.2008.142 ◽

2009 ◽

Vol 58 (1) ◽

pp. 32-45 ◽

Cited By ~ 316

Author(s):

Brett Stanley Feero ◽

Partha Pratim Pande

Keyword(s):

Performance Evaluation ◽

Three Dimensional ◽

Networks On Chip ◽

On Chip ◽

A Performance

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On the effect of long-term electrical stimulation on three-dimensional cell cultures: Hen embryo brain spheroids

Medical Devices Evidence and Research ◽

10.2147/mder.s3245 ◽

2008 ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Ivan Uroukov

Keyword(s):

Electrical Stimulation ◽

Cell Cultures ◽

Three Dimensional ◽

Embryo Brain ◽

Dimensional Cell

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On-chip hydrogel arrays individually encapsulating acoustic formed multicellular aggregates for high throughput drug testing

Lab on a Chip ◽

10.1039/d0lc00255k ◽

2020 ◽

Vol 20 (12) ◽

pp. 2228-2236 ◽

Cited By ~ 5

Author(s):

Xuejia Hu ◽

Shukun Zhao ◽

Ziyi Luo ◽

Yunfeng Zuo ◽

Fang Wang ◽

...

Keyword(s):

Drug Resistance ◽

High Throughput ◽

Solid Tumor ◽

Drug Testing ◽

Three Dimensional ◽

Multicellular Aggregates ◽

3D Environments ◽

On Chip ◽

Insight Into

Multicellular aggregates in three-dimensional (3D) environments provide novel solid tumor models that can provide insight into in vivo drug resistance.

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