Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions

Yamada, Masao; Utoh, Rie; Ohashi, Kazuhiko; Tatsumi, Kohei; Yamato, Masayuki; Okano, Teruo; Seki, Minoru

doi:10.1016/j.biomaterials.2012.07.068

Cited by 227 publications

(227 citation statements)

References 57 publications

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“…Therefore, stability can be defined as a tissue that is not changing with time. This can be determined by tracking material properties [3], matrix content [4], or by other markers of function such as secreted proteins [5–8] or endogenous signals [9, 10]. A homeostatic, ‘stable’ tissue is essential for tissue engineering as a baseline for in vitro studies of the efficacy and toxicity of compounds or to maintain phenotype upon implantation for regenerative applications.…”

Section: Defining ‘Physiological Relevance’ In Tissue Engineering Appmentioning

confidence: 99%

Strategies for improving the physiological relevance of human engineered tissues

Abbott

Kaplan

2015

Trends in Biotechnology

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This review examines important robust methods for sustained, steady state, in vitro culture. To achieve ‘physiologically relevant’ tissues in vitro additional complexity must be introduced to provide suitable transport, cell signaling, and matrix support for cells in 3D environments to achieve stable readouts of tissue function. Most tissue engineering systems draw conclusions on tissue functions such as responses to toxins, nutrition or drugs based on short term outcomes with in vitro cultures (2–14 days). However, short term cultures limit insight with physiological relevance, as the cells and tissues have not reached a steady state.

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Section: Defining ‘Physiological Relevance’ In Tissue Engineering Appmentioning

confidence: 99%

Strategies for improving the physiological relevance of human engineered tissues

Abbott

Kaplan

2015

Trends in Biotechnology

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“…Because hepatic cords consist of aligned single or coupled hepatocytes, this aligned structure can be mimicked by hydrogel microfibers. Yamada et al 50 reported formation of such hepatocyte structures in alginate gel microfibers. Fibroblasts were also embedded in the alginate gel to enhance hepatocyte differentiation via cell−cell communications.…”

Section: Bottom-up Approach: Biomemsmentioning

confidence: 99%

Multiscale tissue engineering for liver reconstruction

Sudo¹

2014

Organogenesis

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The liver is a target of in vitro tissue engineering despite its capability to regenerate in vivo. The construction of liver tissues in vitro remains challenging. In this review, conventional 3D cultures of hepatocytes are first discussed. Recent advances in the 3D culturing of liver cells are then summarized in the context of in vitro liver tissue reconstruction at the micro- and macroscales. The application of microfluidics technology to liver tissue engineering has been introduced as a bottom-up approach performed at the microscale, whereas whole-organ bioengineering technology was introduced as a top-down approach performed at the macroscale. Mesoscale approaches are also discussed in considering the integration of micro- and macroscale approaches. Multiple parallel multiscale liver tissue engineering studies are ongoing; however, no tissue-engineered liver that is appropriate for clinical use has yet been realized. The integration of multiscale tissue engineering studies is essential for further understanding of liver reconstruction strategies.

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“…Alginate is a biocompatible polymer obtained from seaweed, which rapidly gels in the presence of multivalent cations such as Ca 2þ and Ba 2þ . Because of the mild gelation conditions required, alginate hydrogels have been used for a variety of applications, including biological immobilization for bio-production, 39 patterned cell culture, 40 tissue engineering, 41,42 and cell transplantation therapies. 43 In this study, we introduced an aqueous solution of the gelation agent (1M CaCl 2 ) into the microfluidic device (with a dissolution channel length of 70 mm) at the second confluence point, by which time the droplet shrinkage was almost complete.…”

Section: B Production Of Ca-alginate Hydrogel Beadsmentioning

confidence: 99%

Microfluidic production of single micrometer-sized hydrogel beads utilizing droplet dissolution in a polar solvent

et al. 2013

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In this study, a microfluidic process is proposed for preparing monodisperse micrometer-sized hydrogel beads. This process utilizes non-equilibrium aqueous droplets formed in a polar organic solvent. The water-in-oil droplets of the hydrogel precursor rapidly shrunk owing to the dissolution of water molecules into the continuous phase. The shrunken and condensed droplets were then gelled, resulting in the formation of hydrogel microbeads with sizes significantly smaller than the initial droplet size. This study employed methyl acetate as the polar organic solvent, which can dissolve water at 8%. Two types of monodisperse hydrogel beads-Caalginate and chitosan-with sizes of 6-10 lm (coefficient of variation < 6%) were successfully produced. In addition, we obtained hydrogel beads with non-spherical morphologies by controlling the degree of droplet shrinkage at the time of gelation and by adjusting the concentration of the gelation agent. Furthermore, the encapsulation and concentration of DNA molecules within the hydrogel beads were demonstrated. The process presented in this study has great potential to produce small and highly concentrated hydrogel beads that are difficult to obtain by using conventional microfluidic processes. V C 2013 AIP Publishing LLC.

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Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions

Cited by 227 publications

References 57 publications

Strategies for improving the physiological relevance of human engineered tissues

Strategies for improving the physiological relevance of human engineered tissues

Multiscale tissue engineering for liver reconstruction

Microfluidic production of single micrometer-sized hydrogel beads utilizing droplet dissolution in a polar solvent

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