Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures

Fukuda, Junji; Khademhosseini, Ali; Yeo, Yoon; Yang, Xiaoyu; Yeh, Judy; Eng, George; Blumling, James; Wang, Chi Fong; Kohane, Daniel S.; Langer, Robert

doi:10.1016/j.biomaterials.2006.05.044

Cited by 308 publications

(244 citation statements)

References 40 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%

“…Investigators have recently begun to address this limitation by creating micro-scale hydrogels containing viable cells [30]. Photolithographic methods have been used to generate spatially patterned hydrogel structures, in which distinct regions contain specific cell types [31], cell adhesion ligands [32] or ECM chemistries [33,34]. For example, Pishko and coworkers have used photopolymerization within channels [35] or spots [32] to generate PEG microstructures, and demonstrated that multiple mammalian cell types remain viable in spatially patterned hydrogels for up to 7 days.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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“…Patterned hydrogel microstructures have raised notable interest in the fields of biosensing,21 cell culture,22 and cell imaging (for example, neural stem cells23 and spheroids24. Various techniques were reported for fabricating hydrogel microwells in the 100–1000 μm range: replica molding of photocrosslinkable chitosan,24 PEG/heparin multilayered structures,25 or peptide‐based gels,26 soft embossing of PEG gels,23 as well as contact photolithography to pattern PEG‐based materials 22. There is a need for techniques enabling to pattern multiple functional materials with high spatial control.…”

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confidence: 99%

High‐Throughput Contact Flow Lithography

et al. 2015

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High‐throughput fabrication of graphically encoded hydrogel microparticles is achieved by combining flow contact lithography in a multichannel microfluidic device and a high capacity 25 mm LED UV source. Production rates of chemically homogeneous particles are improved by two orders of magnitude. Additionally, the custom‐built contact lithography instrument provides an affordable solution for patterning complex microstructures on surfaces.

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“…1E). Micromolding has also been used to generate microengineered hydrogels from a variety of materials including hyaluronic acid (HA), 36,37 chitosan 38 and PEG. 39 In addition micromolding techniques have been recently adapted to micromold hydrogels such as alginate and fibrin that require the addition of crosslinkers such as divalent cations.…”

Section: Directed Assembly Of Cell-laden Hydrogels For Engineering Timentioning

confidence: 99%