Microvessel manifold for perfusion and media exchange in three-dimensional cell cultures

Roberts, Steven A.; DiVito, Kyle A.; Ligler, Frances S.; Adams, André A.; Daniele, Michael A.

doi:10.1063/1.4963145

Cited by 11 publications

(10 citation statements)

References 62 publications

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“…By day 5, fibroblasts present in the hydrogel display characteristic bipolar, elongated morphology consistent with viable fibroblast expansion (Fig. S6b) [52]. When fibroblasts were excluded, endothelial sprouting was found to be significantly reduced with only short projections of 27 mm median length observed nearest the HEMV lumen at the time of collection on day 21 (Fig.…”

Section: Neoangiogenesismentioning

confidence: 77%

“…Not only does shear stress generate forces that act upon the vessel, but cells undergo morphological changes in response to pulsatile perfusion. Therefore, to illustrate that HEMV support perfusion in a microvessel containing living cells, a novel manifold device [52,55] in conjunction with a peristaltic pump was used to recirculate either growth media or Nile Red microparticles through individual microvessels.…”

Section: Hemv Perfusion and Shear Stress Responsementioning

confidence: 99%

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Microfabricated blood vessels undergo neoangiogenesis

et al. 2017

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The greatest ambition and promise of tissue engineering is to manufacture human organs. Before "made-to-measure" tissues can become a reality [1-3], however, three-dimensional tissues must be reconstructed and characterized. The current inability to manufacture operational vasculature has limited the growth of engineered tissues. Here, free-standing, small diameter blood vessels with organized cell layers that recapitulate normal biological functionality are fabricated using microfluidic technology. Over time in culture, the endothelial cells form a monolayer on the luminal wall and remodel the scaffold with human extracellular matrix proteins. After integration into three-dimensional gels containing fibroblasts, the microvessels sprout and generate extended hollow branches that anastomose with neighboring capillaries to form a network. Both the microfabricated vessels and the extended sprouts support perfusion of fluids and particles. The ability to create cellularized microvessels that can be designed with a diameter of choice, produced by the meter, and undergo angiogenesis and anastomoses will be an extremely valuable tool for vascularization of engineered tissues. To summarize, ultraviolet (UV) photo-crosslinkable poly(ethylene glycol) and gelatin methacrylate polymers used in combination with sheath-flow microfluidics allow for the fabrication of small diameter blood vessels which undergo neoangiogenesis as well as other developmental processes associated with normal human blood vessel maturation. Once mature, these vessels can be embedded; perfused; cryogenically stored and respond to stimuli such as chemokines and shear stresses to mimic native human blood vessels. The applications range from tissue-on-chip systems for drug screening, characterization of normal and pathologic processes, and creation and characterization of engineered tissues for organ repair.

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Section: Neoangiogenesismentioning

confidence: 77%

Section: Hemv Perfusion and Shear Stress Responsementioning

confidence: 99%

Microfabricated blood vessels undergo neoangiogenesis

et al. 2017

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“…For example, PEGDA was shaped by multiaxial flows and formed microtubes after UV‐light exposure . The generated tubes can be integrated within a thick 3D tissue in vitro to enable nutrients supply for the cells in the thick tissue …”

Section: Engineering Approaches On Fabricating Perfusable Microchannementioning

confidence: 99%

Engineering of Hydrogel Materials with Perfusable Microchannels for Building Vascularized Tissues

Xie

Zheng

Guan

et al. 2019

Small

130

117

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Vascular systems are responsible for various physiological and pathological processes related to all organs in vivo, and the survival of engineered tissues for enough nutrient supply in vitro. Thus, biomimetic vascularization is highly needed for constructing both a biomimetic organ model and a reliable engineered tissue. However, many challenges remain in constructing vascularized tissues, requiring the combination of suitable biomaterials and engineering techniques. In this review, the advantages of hydrogels on building engineered vascularized tissues are discussed and recent engineering techniques for building perfusable microchannels in hydrogels are summarized, including micromolding, 3D printing, and microfluidic spinning. Furthermore, the applications of these perfusable hydrogels in manufacturing organ‐on‐a‐chip devices and transplantable engineered tissues are highlighted. Finally, current challenges in recapitulating the complexity of native vascular systems are discussed and future development of vascularized tissues is prospected.

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“…For example, the advent of three‐dimensional culture systems has yielded tremendous insights in biology that were previously difficult or impossible to observe with traditional two‐dimensional culture systems (Kolesky, Homan, Skylar‐Scott, & Lewis, ; Laschke & Menger, ). Moreover, the use of perfusion devices, which can deliver media throughout a tissue construct, has been instrumental in overcoming the limits of gas and nutrient diffusion that would otherwise lead to necrosis (Gao et al., ; Huang et al., ; Karimi et al., ; Prodanov et al., ; Roberts, DiVito, Ligler, Adams, & Daniele, ; Zhang, Wang, Hui, Qiu, & Wang, ). However, the use of these perfusion approaches to control soluble factor delivery, and therefore morphogen presentation to embedded cells, has not been explored in great depth.…”

Section: Commentarymentioning

confidence: 99%

“…Current Protocols in Stem Cell Biology can deliver media throughout a tissue construct, has been instrumental in overcoming the limits of gas and nutrient diffusion that would otherwise lead to necrosis (Gao et al, 2017;Huang et al, 2011;Karimi et al, 2016;Prodanov et al, 2016;Roberts, DiVito, Ligler, Adams, & Daniele, 2016;Zhang, Wang, Hui, Qiu, & Wang, 2017). However, the use of these perfusion approaches to control soluble factor delivery, and therefore morphogen presentation to embedded cells, has not been explored in great depth.…”

Section: Of 21mentioning

confidence: 99%

Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three‐Dimensional Hydrogels

O’Grady

Balikov

Lippmann

et al. 2019

CP Stem Cell Biology

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Morphogens are biological molecules that alter cellular identity and behavior across both space and time. During embryonic development, morphogen spatial localization can be confined to small volumes in a single tissue or permeate throughout an entire organism, and the temporal effects of morphogens can range from fractions of a second to several days. In most cases, morphogens are presented as a gradient to adjacent cells within tissues to pattern cell fate. As such, to appropriately model development and build representative multicellular architectures in vitro, it is vital to recapitulate these gradients during stem cell differentiation. However, the ability to control morphogen presentation within in vitro systems remains challenging. Here, we describe an innovative platform using channels patterned within thick, three‐dimensional hydrogels that deliver multiple morphogens to embedded cells, thereby demonstrating exquisite control over both spatial and temporal variations in morphogen presentation. This generalizable approach should have broad utility for researchers interested in patterning in vitro tissue structures. © 2019 by John Wiley & Sons, Inc.

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Microvessel manifold for perfusion and media exchange in three-dimensional cell cultures

Cited by 11 publications

References 62 publications

Microfabricated blood vessels undergo neoangiogenesis

Microfabricated blood vessels undergo neoangiogenesis

Engineering of Hydrogel Materials with Perfusable Microchannels for Building Vascularized Tissues

Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three‐Dimensional Hydrogels

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