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High-throughput fabrication of vascularized spheroids for bioprinting

(2018) BIOFABRICATION. 10(3).
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Abstract
Overcoming the problem of vascularization remains the main challenge in the field of tissue engineering. As three-dimensional (3D) bioprinting is the rising technique for the fabrication of large tissue constructs, small prevascularized building blocks were generated that can be incorporated throughout a printed construct, answering the need for a microvasculature within the small micron range (<10 mu m). Uniform spheroids with an ideal geometry and diameter for bioprinting were formed, using a high-throughput non-adhesive agarose microwell system. Since monoculture spheroids of endothelial cells were unable to remain stable, coculture spheroids combining endothelial cells with fibroblasts and/or adipose tissue derived mesenchymal stem cells (ADSC) as supporting cells, were created. When applying the favorable coculture ratio, viable spheroids were obtained and endothelial cells spontaneously formed a capillary-like network and lumina, as shown by immunohistochemistry and transmission electron microscopy. Especially the presence of ADSC led to a higher vascularization and extracellular matrix production of the microtissue. Moreover, spheroids were able to assemble at random in suspension and in a hydrogel, creating a macrotissue. During at random assembly, cells reorganized, creating a branched capillary-network throughout the entire fused construct by inoculating with capillaries of adjacent spheroids. Combining the advantage of this natural capacity of microtissues to self-assemble and the controlled organization by bioprinting technologies, these prevascularized spheroids can be useful as building blocks for the engineering of large vascularized 3D tissues.
Keywords
spheroids, vascularization, coculture, scaffold-free, 3D culture, bioprinting, MESENCHYMAL STEM-CELLS, BLOOD-VESSEL FORMATION, PREVASCULARIZED MICROTISSUE SPHEROIDS, ENDOTHELIAL-CELLS, IN-VITRO, DIFFERENTIAL ADHESION, NETWORK FORMATION, ADIPOSE-TISSUE, BONE-MARROW, ANGIOGENESIS

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Citation

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MLA
De Moor, Lise, Idriz Merovci, Sarah Baetens, et al. “High-throughput Fabrication of Vascularized Spheroids for Bioprinting.” BIOFABRICATION 10.3 (2018): n. pag. Print.
APA
De Moor, L., Merovci, I., Baetens, S., Verstraeten, J., Kowalska, P., Krysko, D., De Vos, W., et al. (2018). High-throughput fabrication of vascularized spheroids for bioprinting. BIOFABRICATION, 10(3).
Chicago author-date
De Moor, Lise, Idriz Merovci, Sarah Baetens, Julien Verstraeten, Paulina Kowalska, Dmitri Krysko, Winnok De Vos, and Heidi Declercq. 2018. “High-throughput Fabrication of Vascularized Spheroids for Bioprinting.” Biofabrication 10 (3).
Chicago author-date (all authors)
De Moor, Lise, Idriz Merovci, Sarah Baetens, Julien Verstraeten, Paulina Kowalska, Dmitri Krysko, Winnok De Vos, and Heidi Declercq. 2018. “High-throughput Fabrication of Vascularized Spheroids for Bioprinting.” Biofabrication 10 (3).
Vancouver
1.
De Moor L, Merovci I, Baetens S, Verstraeten J, Kowalska P, Krysko D, et al. High-throughput fabrication of vascularized spheroids for bioprinting. BIOFABRICATION. 2018;10(3).
IEEE
[1]
L. De Moor et al., “High-throughput fabrication of vascularized spheroids for bioprinting,” BIOFABRICATION, vol. 10, no. 3, 2018.
@article{8567547,
  abstract     = {{Overcoming the problem of vascularization remains the main challenge in the field of tissue engineering. As three-dimensional (3D) bioprinting is the rising technique for the fabrication of large tissue constructs, small prevascularized building blocks were generated that can be incorporated throughout a printed construct, answering the need for a microvasculature within the small micron range (<10 mu m). Uniform spheroids with an ideal geometry and diameter for bioprinting were formed, using a high-throughput non-adhesive agarose microwell system. Since monoculture spheroids of endothelial cells were unable to remain stable, coculture spheroids combining endothelial cells with fibroblasts and/or adipose tissue derived mesenchymal stem cells (ADSC) as supporting cells, were created. When applying the favorable coculture ratio, viable spheroids were obtained and endothelial cells spontaneously formed a capillary-like network and lumina, as shown by immunohistochemistry and transmission electron microscopy. Especially the presence of ADSC led to a higher vascularization and extracellular matrix production of the microtissue. Moreover, spheroids were able to assemble at random in suspension and in a hydrogel, creating a macrotissue. During at random assembly, cells reorganized, creating a branched capillary-network throughout the entire fused construct by inoculating with capillaries of adjacent spheroids. Combining the advantage of this natural capacity of microtissues to self-assemble and the controlled organization by bioprinting technologies, these prevascularized spheroids can be useful as building blocks for the engineering of large vascularized 3D tissues.}},
  articleno    = {{035009}},
  author       = {{De Moor, Lise and Merovci, Idriz and Baetens, Sarah and Verstraeten, Julien and Kowalska, Paulina and Krysko, Dmitri and De Vos, Winnok and Declercq, Heidi}},
  issn         = {{1758-5082}},
  journal      = {{BIOFABRICATION}},
  keywords     = {{spheroids,vascularization,coculture,scaffold-free,3D culture,bioprinting,MESENCHYMAL STEM-CELLS,BLOOD-VESSEL FORMATION,PREVASCULARIZED MICROTISSUE SPHEROIDS,ENDOTHELIAL-CELLS,IN-VITRO,DIFFERENTIAL ADHESION,NETWORK FORMATION,ADIPOSE-TISSUE,BONE-MARROW,ANGIOGENESIS}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{14}},
  title        = {{High-throughput fabrication of vascularized spheroids for bioprinting}},
  url          = {{http://dx.doi.org/10.1088/1758-5090/aac7e6}},
  volume       = {{10}},
  year         = {{2018}},
}

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