Simple Precision Creation of Digitally Specified, Spatially Heterogeneous, Engineered Tissue Architectures

Gürkan, Umut A.; Fan, Yantao; Xu, Feng; Erkmen, Burcu; Urkac, Emel Sokullu; Parlakgül, Güneş; Bernstein, Jared; Xing, Wangli; Boyden, Edward S.; Demirci, Utkan

doi:10.1002/adma.201203261

Cited by 65 publications

(68 citation statements)

References 52 publications

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“…The 3D brain-like tissue growth was found to be affected by neuron densities. The axons showed a tendency to extend long distances over available space and form connections with neighboring neurons, consistent with other reports of hydrogel-based 3D neuronal systems (6). Two-dimensional cultures and collagen gel-based 3D cultures were used as control systems with cell numbers determined by DNA quantitation (Materials and Methods and Fig.…”

Section: Resultssupporting

confidence: 60%

Bioengineered functional brain-like cortical tissue

Tang-Schomer¹,

White²,

Tien³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

265

299

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The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.electrophysiology | connectivity | silk | scaffold | traumatic brain injury

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Section: Resultssupporting

confidence: 60%

Bioengineered functional brain-like cortical tissue

Tang-Schomer¹,

White²,

Tien³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

265

299

View full text Add to dashboard Cite

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“…1. Lithography and mask fabrication methods have also been adapted to tissue engineering and biological systems [33]. (II) Nano-embossing is a promising method of nanostructure preparation, enabling inexpensive and high throughput nanofabrication.…”

Section: Nanostructure Preparation Techniquesmentioning

confidence: 99%

Nanostructured substrates for isolation of circulating tumor cells

et al. 2013

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Summary Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. CTCs hold the key to understanding the biology of metastasis and also play a vital role in cancer diagnosis, prognosis, disease monitoring, and personalized therapy. However, CTCs are rare in blood and hard to isolate. Additionally, the viability of CTCs can easily be compromised under high shear stress while releasing them from a surface. The heterogeneity of CTCs in biomarker expression makes their isolation quite challenging; the isolation efficiency and specificity of current approaches need to be improved. Nanostructured substrates have emerged as a promising biosensing platform since they provide better isolation sensitivity at the cost of specificity for CTC isolation. This review discusses major challenges faced by CTC isolation techniques and focuses on nanostructured substrates as a platform for CTC isolation.

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“…The recent emergence of microfabricated 3D biomaterials systems may provide a potential solution for this problem. Bioprinting techniques [19, 20] and photolithography-based patterning techniques [13, 21] have been used to build 3D tissues that are of millimeter and even smaller length scales. The small size of these microtissues enables the study of structural remodeling from micro to macoscopic tissue levels.…”

Section: Introductionmentioning

confidence: 99%

Force-driven evolution of mesoscale structure in engineered 3D microtissues and the modulation of tissue stiffening

2014

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The complex structures of tissues determine their mechanical strength. In engineered tissues formed through self-assembly in a mold, artificially imposed boundary constraints have been found to induce anisotropic clustering of the cells and the extracellular matrix in local regions. To understand how such tissue remodeling at the intermediate length-scale (mesoscale) affects tissue stiffening, we used a novel microtissue mechanical testing system to manipulate the remodeling of the tissue structures and to measure the subsequent changes in tissue stiffness. Microtissues were formed through cell driven self-assembly of collagen matrix in arrays of micro-patterned wells, each containing two flexible micropillars that measured the microtissues’ contractile forces and also their elastic moduli via magnetic actuation. We manipulated tissue remodeling by inducing myofibroblast differentiation with TGF-β1, by varying the micropillar spring constants or by blocking cell contractility with blebbistatin and collagen cross-linking with BAPN. We showed that increased anisotropic compaction of the collagen matrix, caused by increased micropillar spring constant or elevated cell contraction force, contributed to tissue stiffening. Conversely, collagen matrix and tissue stiffness were not affected by inhibition of cell-generated contraction forces.. Together, these measurements showed that mesoscale tissue remodeling is an important middle step linking tissue compaction forces and tissue stiffening.

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Simple Precision Creation of Digitally Specified, Spatially Heterogeneous, Engineered Tissue Architectures

Cited by 65 publications

References 52 publications

Bioengineered functional brain-like cortical tissue

Bioengineered functional brain-like cortical tissue

Nanostructured substrates for isolation of circulating tumor cells

Force-driven evolution of mesoscale structure in engineered 3D microtissues and the modulation of tissue stiffening

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