Two‐Dimensional Multiarray Formation of Hepatocyte Spheroids on a Microfabricated PEG‐Brush Surface

Otsuka, Hidenori; Hirano, Atsushi; Nagasaki, Yukio; Okano, Teruo; Horiike, Yasuhiro; Kataoka, Kazunori

doi:10.1002/cbic.200300822

Cited by 134 publications

(94 citation statements)

References 30 publications

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“…[74][75][76] One application of interest is the use of cell spheroids (Fig. 2B), such as those made from embryonic stem cells (as discussed above), hepatocytes, 77 mesenchymal stem cells, 78 neural stem cells 70 or tumor cells. 79 However, it should be noted that microwells do not provide any new functionality compared to conventional cell culture systems.…”

Section: Discussionmentioning

confidence: 99%

Integration column: microwell arrays for mammalian cell culture

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Integration column: microwell arrays for mammalian cell culture

et al. 2009

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“…Hepatocyte spheroids constructed by patterning technology are expected to be an alternative for animal experiments in drug screening. 33 On the other hand, there is a major technical barrier to the use of micropatterned cells for future transplantation, because of difficulties in dissociating cells from substrates, such as glass, silicon, gold, metal oxides and polymeric materials, without a loss of the constructed structures. Creating cell micropatterns on biocompatible or biodegradable biomaterials 34,35 or poly(Nisopropylacrylamide), [36][37][38] a smart material that allows dissociation of a contiguous cell sheet accompanying extracellular matrices, overcomes this issue.…”

Section: ·3 Tissue Engineeringmentioning

confidence: 99%

Recent Advances in Cell Micropatterning Techniques for Bioanalytical and Biomedical Sciences

et al. 2008

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Cell micropatterning is a method for controlling the placement of living cells on a substrate surface. [1][2][3][4][5][6][7][8] It is important for a wide range of applications, such as tissue engineering, cellbased drug screening, and fundamental cell biology studies. Most cell micropatterning methods fall into three categories based on strategy: (1) seeding cells on a chemically patterned surface of different cell adhesiveness, (2) seeding cells on a topographically patterned surface, or (3) directed delivery of cells onto discrete regions of a substrate. Although the latter two categories are also important, this review mainly focuses on the first category. This is because it is the most common strategy and it provides tools to study fundamental aspects of cell adhesion at the single protein/receptor molecule level. 9There are excellent reviews that also cover the latter two categories. 3,8,10 We first introduce some of the important applications of cell micropatterning in general. We then describe methods for micropatterning the cell adhesiveness, referring to materials that promote or inhibit cell adhesion. We then move on to much more sophisticated substrates, so-called "dynamic substrates", whose cell adhesiveness can be changed by an external stimulus, such as heat, voltage and light. As an example of dynamic substrates, we describe a caged culture substrate developed by our group. This type of functional substrate opens up new possibilities in bioanalytical and biomedical sciences. Cell micropatterning is an important technique for a wide range of applications, such as tissue engineering, cell-based drug screening, and fundamental cell biology studies. This paper overviews cell patterning techniques based on chemically modified substrates with different degrees of cell adhesiveness. In particular, the focus is on dynamic substrates that change their cell adhesiveness in response to external stimuli, such as heat, voltage, and light. Such substrates allow researchers to achieve an in situ alteration of patterns of cell adhesiveness, which is useful for coculturing multiple cell types and analyzing dynamic cellular activities. As an example of dynamic substrates, we introduce a dynamic substrate based on a caged compound, where we accomplished a light-driven alteration of cell adhesiveness and the analysis of a single cell's motility.

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“…As isolated primary cells are known to readily lose many cell-specific functions during culture, the most crucial issues in CBBs are long-term viability and retention of cell-specific functions of cultured cells. In this regards, the formation of multicellular spheroids is of particular interest because spheroids show not only morphological but also functional similarities to tissues and organs [5,6]. In this study, two-dimensional microarrays of cell-adhesive circular domains (φ = 100 µm), surrounded by poly(ethylene glycol) (PEG) hydrogel, were prepared by photolithography to promote adhesion and spheroid formation of chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Chondrocyte spheroids on microfabricated PEG hydrogel surface and their noninvasive functional monitoring

Otsuka

Nagamura

Kaneko

et al. 2012

Science and Technology of Advanced Materials

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A two-dimensional microarray of 10 000 (100 × 100) chondrocyte spheroids was constructed with a 100 µm spacing on a micropatterned gold electrode that was coated with poly(ethylene glycol) (PEG) hydrogels. The PEGylated surface as a cytophobic region was regulated by controlling the gel structure through photolithography. In this way, a PEG hydrogel was modulated enough to inhibit outgrowth of chondrocytes from a cell adhering region in the horizontal direction, which is critical for inducing formation of three-dimensional chondrocyte aggregations (spheroids) within 24 h. We further report noninvasive monitoring of the cellular functional change at the cell membrane using a chondrocyte-based field effect transistor. This measurement is based on detection of extracellular potential change induced as a result of the interaction between extracellular matrix protein secreted from spheroid and substrate at the cell membrane. The interface potential change at the cell membrane/gate interface can be monitored during the differentiation of spheroids without any labeling materials. Our measurements of the time evolution of the interface potential provide important information for understanding the uptake kinetics for cellular differentiation.

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Two‐Dimensional Multiarray Formation of Hepatocyte Spheroids on a Microfabricated PEG‐Brush Surface

Cited by 134 publications

References 30 publications

Integration column: microwell arrays for mammalian cell culture

Integration column: microwell arrays for mammalian cell culture

Recent Advances in Cell Micropatterning Techniques for Bioanalytical and Biomedical Sciences

Chondrocyte spheroids on microfabricated PEG hydrogel surface and their noninvasive functional monitoring

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