PEG‐fibrinogen hydrogels for three‐dimensional breast cancer cell culture

Pradhan, Shantanu; Hassani, Iman; Seeto, Wen J.; Lipke, Elizabeth A.

doi:10.1002/jbm.a.35899

Cited by 69 publications

(84 citation statements)

References 61 publications

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“…Many groups have developed biomaterial cell culture platforms and suggested that future applications could include drug screening. [4][5][46][47] These materials could have significant impact on improving the data obtained by in vitro cell studies, if adapted to current high-throughput screening technologies. Towards this goal, we adapted our lab's existing biomaterial technologies to 96-well plates and semi-automated liquid handling robotics.…”

Section: Discussionmentioning

confidence: 99%

Complementary, Semi-automated Methods for Creating Multi-dimensional, PEG-based Biomaterials

Brooks

Jansen

Gencoglu

et al. 2017

Preprint

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Tunable biomaterials that mimic selected features of the extracellular matrix (ECM), such as its stiffness, protein composition, and dimensionality, are increasingly popular for studying how cells sense and respond to ECM cues. In the field, there exists a significant trade-off for how complex and how well these biomaterials represent the in vivo microenvironment, versus how easy they are to make and how adaptable they are to high-throughput fabrication techniques. To address this need to integrate more complex biomaterials design with high-throughput screening approaches, we present several methods to fabricate synthetic biomaterials in 96-well plates and demonstrate that they can be adapted to existing liquid handling robotics. These platforms include 1) glass bottom plates with covalently attached ECM proteins, and 2) hydrogels with tunable stiffness and protein composition with either cells seeded on the surface, or 3) laden within the three-dimensional hydrogel matrix. This study includes proof-of-concept results demonstrating control over breast cancer cell line phenotypes via these ECM cues in a highthroughput fashion. We foresee the use of these methods as a mechanism to bridge the gap between high-throughput cell-matrix screening and engineered ECM-mimicking biomaterials.

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Section: Discussionmentioning

confidence: 99%

Complementary, Semi-automated Methods for Creating Multi-dimensional, PEG-based Biomaterials

Brooks

Jansen

Gencoglu

et al. 2017

Preprint

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“…[9,72] However, MDA-MB-231 breast cancer cells, which are noted for their aggressive, invasive phenotype, did not cluster in the gels but rather showed a more disordered, spread morphology, with protrusions into the surrounding matrix. [71] Collectively, these results suggest that the engineered PEG-fibrinogen platform is a suitable surrogate for Matrigel in breast cancer studies. Building on this work, a subsequent study used the PEG-fibrinogen platform to produce MCF-7 breast cancer cell spheroids via microsphere encapsulation in the hydrogels.…”

Section: Breast Cancermentioning

confidence: 90%

“…As one example, Pradhan et al utilized fibrinogen-conjugated PEG diacrylate crosslinked via a radicalinitiated chain polymerization to encapsulate breast cancer cells. [71] They adjusted the stiffness of the gels from 3.2 ± 0.5 kPa to 5.4 ± 0.5 kPa to 9.0 ± 1.4 kPa (Young's modulus) by introducing increasing concentrations of PEG diacrylate that was not fibrinogen-conjugated to the gel and observed that two breast cancer cell lines, MCF-7 and SK-BR-3, formed cell clusters after 15 days of culture and had comparable morphologies across gels of differing stiffness. These cells formed orderly spherical cell clusters, similar to the acini-like structures observed in Matrigel.…”

Section: Breast Cancermentioning

confidence: 99%

Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics

2017

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Tissue engineering holds great promise for advancing cancer research and achieving the goals of the Cancer Moonshot by providing better models for basic research and testing novel therapeutics. This paper focuses on the use of hydrogel biomaterials due to their unique ability to entrap cells in three-dimensional (3D) matrix that mimics tissues and can be programmed with physical and chemical cues to recreate key aspects of tumor microenvironments. The chemistry of some commonly used hydrogel platforms is discussed, and important examples of their use in tissue engineering 3D cancer models are highlighted. Challenges and opportunities for future research are also discussed.

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“…PEG-fibrinogen precursors were used to synthesize microspheres of adjustable stiffness and porosity for 3D culture of breast cancer cells MCF-7, SK-BR-3, and MDA-MB-231. [111] Cancer cells pre-mixed with the PEG-fibrinogen polymer precursor were suspended on a polydimethylsiloxane substrate and photo-crosslinked to form cancer cell-containing hydrogel microspheres. Hydrogels degraded over time and cells proliferated.…”

Section: 2 Synthetic Materialsmentioning

confidence: 99%

Biomaterials‐Based Approaches to Tumor Spheroid and Organoid Modeling

Thakuri

Liu

Luker

et al. 2017

Adv Healthcare Materials

109

100

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Evolving understanding of structural and biological complexity of tumors has stimulated development of physiologically relevant tumor models for cancer research and drug discovery. A major motivation for developing new tumor models is to recreate the 3D environment of tumors and context-mediated functional regulation of cancer cells. Such models overcome many limitations of standard monolayer cancer cell cultures. Under defined culture conditions, cancer cells self-assemble into 3D constructs known as spheroids. Additionally, cancer cells may recapitulate steps in embryonic development to self-organize into 3D cultures known as organoids. Importantly, spheroids and organoids reproduce morphology and biologic properties of tumors, providing valuable new tools for research, drug discovery, and precision medicine in cancer. This Progress Report discusses uses of both natural and synthetic biomaterials to culture cancer cells as spheroids or organoids, specifically highlighting studies that demonstrate how these models recapitulate key properties of native tumors. The report concludes with the perspectives on the utility of these models and areas of need for future developments to more closely mimic pathologic events in tumors.

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PEG‐fibrinogen hydrogels for three‐dimensional breast cancer cell culture

Cited by 69 publications

References 61 publications

Complementary, Semi-automated Methods for Creating Multi-dimensional, PEG-based Biomaterials

Complementary, Semi-automated Methods for Creating Multi-dimensional, PEG-based Biomaterials

Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics

Biomaterials‐Based Approaches to Tumor Spheroid and Organoid Modeling

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