Hydrogel-based methods for engineering cellular microenvironment with spatiotemporal gradients

Wang, Lin; Li, Yuhui; Huang, Guangsu; Zhang, Xiaohui; Murphy, Belinda; Gao, Bin; Lu, Tian Jian; Xu, Feng

doi:10.3109/07388551.2014.993588

Cited by 39 publications

(33 citation statements)

References 116 publications

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“…After that, varied biodegradability alginate hydrogel were printed with human cells to investigate cell response . Lin Wang's review systematically introduced hydrogel‐based methods for engineering cellular microenvironment with spatiotemporal gradients . Although the content introduced in this article is limited, there are many degradation and stability test methods introduced by others.…”

Section: Conclusion and Future Prospectivementioning

confidence: 99%

“…Mechanical properties are key parameters when designing hydrogels for specific tissue engineering applications . The hydrogel stiffness influences cell behavior and can serve as multidimensional cell culture platforms to further mimic the intravital niche . The stiffness of hyaluronic acid (HA) gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.…”

Section: Introductionmentioning

confidence: 99%

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A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine

Xia

Liu

Yang

2017

J Biomedical Materials Res

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Substrate stiffness is known to impact characteristics including cell differentiation, proliferation, migration and apoptosis. Hydrogels are polymeric materials distinguished by high water content and diverse physical properties. Gradient stiffness hydrogels are designed by the need to develop biologically friendly materials as extracellular matrix (ECM) alternatives to replace the separated and narrow-ranged hydrogel substrates. Important new discoveries in cell behaviors have been realized with model gradient stiffness hydrogel systems from the two-dimensional (2D) to three-dimensional (3D) scale. Basic and clinical applications for gradient stiffness hydrogels in tissue engineering and regenerative medicine continue to drive the development of stiffness and structure varied hydrogels. Given the importance of gradient stiffness hydrogels in basic research and biomedical applications, there is a clear need for systems for gradient stiffness hydrogel design strategies and their applications. This review will highlight past work in the field of gradient stiffness hydrogels fabrication methods, mechanical property test, applications as well as areas for future study. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1799-1812, 2017.

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Section: Conclusion and Future Prospectivementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine

Xia

Liu

Yang

2017

J Biomedical Materials Res

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“…[1][2][3][4] Cells sense and respond to mechanical cues, such as the mechanical strains and the rigidity of their extracellular matrix (ECM), by adjusting the transmembrane molecules (e.g., integrins) and by reorganizing the intracellular cytoskeleton. 5,6 Tools for studying strain responses of cells in two-dimensional (2D) environment, including stretchable substrata, 7 micropost arrays 8 and 2D traction microscopy, 9 are well established.…”

Section: Introductionmentioning

confidence: 99%

Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

Huang

Gao

et al. 2016

NPG Asia Mater

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Living cells respond to their mechanical microenvironments during development, healing, tissue remodeling and homeostasis attainment. However, this mechanosensitivity has not yet been established definitively for cells in three-dimensional (3D) culture environments, in part because of challenges associated with providing uniform and consistent 3D environments that can deliver a large range of physiological and pathophysiological strains to cells. Here, we report microscale magnetically actuated, cell-laden hydrogels (μMACs) for investigating the strain-induced cell response in 3D cultures. μMACs provide high-throughput arrays of defined 3D cellular microenvironments that undergo reversible, relatively homogeneous deformation following non-contact actuation under external magnetic fields. We present a technique that not only enables the application of these high strains (60%) to cells but also enables simplified microscopy of these specimens under tension. We apply the technique to reveal cellular strain-threshold and saturation behaviors that are substantially different from their 2D analogs, including spreading, proliferation, and differentiation. μMACs offer insights for mechanotransduction and may also provide a view of how cells respond to the extracellular matrix in a 3D manner.

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“…Recently, advanced tools have been developed to accurately mimic natural tumor microenvironments composed of ECM, vasculature, and supporting stromal cells (141, 142). These innovative approaches include 3D coculture systems, micropatterning, microfluidics, and 3D bioprinting, which provide unique opportunities to recapitulate complex and sophisticated tumor microenvironments, such as multicellular microenvironments and spatiotemporal gradients of various physicochemical and biological cues.…”

Section: Emerging Techniques To Create Engineered Tumor/tumor Angimentioning

confidence: 99%

Bioinspired Hydrogels to Engineer Cancer Microenvironments

Park

Lewis

Gerecht

2017

Annu. Rev. Biomed. Eng.

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Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen tension, pH, cytokines, and matrix stiffness. An emerging trend in cancer research involves the creation of engineered three-dimensional tumor models using bioinspired hydrogels that accurately recapitulate the native tumor microenvironment. With recent advances in materials engineering, many researchers are developing engineered tumor models, which are promising platforms for the study of cancer biology and for screening of therapeutic agents for better clinical outcomes. In this review, we discuss the development and use of polymeric hydrogel materials to engineer native tumor ECMs for cancer research, focusing on emerging technologies in cancer engineering that aim to accelerate clinical outcomes.

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Hydrogel-based methods for engineering cellular microenvironment with spatiotemporal gradients

Cited by 39 publications

References 116 publications

A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine

A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine

Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

Bioinspired Hydrogels to Engineer Cancer Microenvironments

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