A cell-laden microfluidic hydrogel

Ling, Yibo; Rubin, Jamie; Deng, Yuting; Huang, Chen; Demirci, Utkan; Karp, Jeffrey M.; Khademhosseini, Ali

doi:10.1039/b615486g

Cited by 355 publications

(353 citation statements)

References 45 publications

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“…Previous studies in 2-D and 3-D culture work have used photolithographic techniques [31,[33][34][35], laminar flow [36,[49][50][51][52], and combinations thereof [32,53,54], to generate microarrays of photo-reactive polymers. Although these previous studies provide valuable insights into the effects of ECM signals on cell behavior, photolithographic techniques are typically limited to the use of photo-reactive polymers, and laminar flow is dimensionally limited to micro-scale materials.…”

Section: Discussionmentioning

confidence: 99%

An adaptable hydrogel array format for 3-dimensional cell culture and analysis

et al. 2008

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Hydrogels have been commonly used as model systems for 3-dimensional (3-D) cell biology, as they have material properties that resemble natural extracellular matrices (ECMs), and their cellinteractive properties can be readily adapted in order to address a particular hypothesis. Natural and synthetic hydrogels have been used to gain fundamental insights into virtually all aspects of cell behavior, including cell adhesion, migration, and differentiated function. However, cell responses to complex 3-D environments are difficult to adequately explore due to the large number of variables that must be controlled simultaneously. Here we describe an adaptable, automated approach for 3-D cell culture within hydrogel arrays. Our initial results demonstrate that the hydrogel network chemistry (both natural and synthetic), cell type, cell density, cell adhesion ligand density, and degradability within each array spot can be systematically varied to screen for environments that promote cell viability in a 3-D context. In a testbed application we then demonstrate that a hydrogel array format can be used to identify environments that promote viability of HL-1 cardiomyocytes, a cell line that has not been cultured previously in 3-D hydrogel matrices. Results demonstrate that the fibronectin-derived cell adhesion ligand RGDSP improves HL-1 viability in a dose-dependent manner, and that the effect of RGDSP is particularly pronounced in degrading hydrogel arrays. Importantly, in the presence of 70µM RGDSP, HL-1 cardiomyocyte viability does not decrease even after 7 days of culture in PEG hydrogels. Taken together, our results indicate that the adaptable, array-based format developed in this study may be useful as an enhanced throughput platform for 3-D culture of a variety of cell types.

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Section: Discussionmentioning

confidence: 99%

An adaptable hydrogel array format for 3-dimensional cell culture and analysis

et al. 2008

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“…Such advances allow the introduction of spatially specific cues in hydrogels, making multicellular constructs, either through co-cultures or multilineage differentiation, a possibility [16][17][18] . Spatial patterning of hydrogels also provides an additional tool for the development of high-throughput screening technology for the rapid investigation of cell-material interactions [19][20][21][22] .…”

Section: Static Hydrogels That Mimic Biophysical Cuesmentioning

confidence: 99%

Moving from static to dynamic complexity in hydrogel design

2012

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Hydrogels are water-swollen polymer networks that have found a range of applications from biological scaffolds to contact lenses. Historically, their design has consisted primarily of static systems and those that exhibit simple degradation. However, advances in polymer synthesis and processing have led to a new generation of dynamic systems that are capable of responding to artificial triggers and biological signals with spatial precision. These systems will open up new possibilities for the use of hydrogels as model biological structures and in tissue regeneration.H ydrogels are water-swollen polymer networks that have been used for many decades, with applications as varied as contact lenses and super-absorbant materials. As the field of biomedical engineering has developed, hydrogels have become a prime candidate for application as molecule delivery vehicles and as carriers for cells in tissue engineering, owing to their ability to mimic many aspects of the native cellular environment (for example, high water content, mechanical properties that match soft tissues). Traditional hydrogels, formed through the covalent and non-covalent crosslinking of polymer chains, were regarded as relatively inert materials, providing a simple biomimetic three-dimensional (3D) environment, either for tissue production by local resident cells or for positioning of cells delivered in vivo. However, the simplicity of these materials may have in fact hindered their application, restricting cellular interactions with the environment and preventing uniform extracellular matrix (ECM) production and proper tissue development. In addition, these materials were limited to modelling static environments and lacked the spatiotemporal dynamic properties relevant for complex tissue processes. Fortunately, during the last decade the concepts of hydrogel design and cellular interaction have evolved, shedding light on how they may control cell behaviour, particularly for tissue engineering applications.Hydrogels with a range of mechanical properties, and capable of incorporating a wide range of biologically relevant molecules, from individual functional groups to multidomain proteins, are currently in development 1 . In addition, hydrogels are being designed with spatial heterogeneity, to either replicate properties in native tissue structures or to produce constructs with distinct regionally specific cell behavior 2 . As a result, studies to date have clearly demonstrated the possibility of creating well-defined microenvironments with control over the 3D presentation of signals to cells 3 . However, recently there has been a focus on the concept of hydrogels that exhibit dynamic complexity. These materials should evolve with time and in response to

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“…Since then, we have extended their approach to ECM gels using chaotropes and other perturbants (such as glycerol for type I collagen), and others have shown that silk and agarose gels are also amenable to bonding. 4,23,38 By iteratively molding, stacking, and bonding thin layers of alginate, Zheng et al 58 recently showed that three-dimensional interconnected microscale networks could be constructed within gels.…”

Section: Micromoldingmentioning

confidence: 99%

Microstructured extracellular matrices in tissue engineering and development

Nelson

Tien

2006

Current Opinion in Biotechnology

106

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Abstract-Microstructured extracellular matrix (ECM), which contains heterogeneous features of the same size scale (5-100 lm) as tissue organoids, has become an important material for the engineering of functional tissues and for the study of tissue-level biology. This review describes methods to generate this class of ECM, and highlights recent advances in the application of microstructured ECM to problems in basic and applied biology. It also discusses computational techniques to analyze and optimize the microstructural patterns for a desired functional output.

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A cell-laden microfluidic hydrogel

Cited by 355 publications

References 45 publications

An adaptable hydrogel array format for 3-dimensional cell culture and analysis

An adaptable hydrogel array format for 3-dimensional cell culture and analysis

Moving from static to dynamic complexity in hydrogel design

Microstructured extracellular matrices in tissue engineering and development

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