Toward 3D-bioprinting of an endocrine pancreas: a building-block concept for bioartificial insulin-secreting tissue

Three-dimensional bioprinting of an endocrine pancreas is a promising future curative treatment for patients with insulin secretion deficiency. In this study, we present an end-to-end concept from the molecular to the macroscopic level. Building-blocks for a hybrid scaffold device of hydrogel and fu...

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Main Authors: Salg, Gabriel Alexander (Author) , Zillich, Eric (Author) , Neulinger-Muñoz, Matthias (Author) , Gerhardus, Jamina (Author) , Cebulla, Daniel (Author) , Bludszuweit-Philipp, Catrin (Author) , Vieira, Vitor Manuel Machado (Author) , Nickel, Felix (Author) , Herr, Ingrid (Author) , Blaeser, Andreas (Author) , Giese, Nathalia (Author) , Hackert, Thilo (Author) , Kenngott, Hannes Götz (Author)
Format: Article (Journal)
Language:English
Published: 2022
In: Journal of tissue engineering
Year: 2022, Volume: 13, Pages: 1-19
ISSN:2041-7314
DOI:10.1177/20417314221091033
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1177/20417314221091033
Verlag, kostenfrei, Volltext: https://journals.sagepub.com/doi/10.1177/20417314221091033
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Author Notes:Gabriel A Salg, Eric Poisel, Matthias Neulinger-Munoz, Jamina Gerhardus, Daniel Cebulla, Catrin Bludszuweit-Philipp, Vitor Vieira, Felix Nickel, Ingrid Herr, Andreas Blaeser, Nathalia A Giese, Thilo Hackert and Hannes G Kenngott
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Summary:Three-dimensional bioprinting of an endocrine pancreas is a promising future curative treatment for patients with insulin secretion deficiency. In this study, we present an end-to-end concept from the molecular to the macroscopic level. Building-blocks for a hybrid scaffold device of hydrogel and functionalized polycaprolactone were manufactured by 3D-(bio)printing. Pseudoislet formation from INS-1 cells after bioprinting resulted in a viable and proliferative experimental model. Transcriptomics showed an upregulation of proliferative and ß-cell-specific signaling cascades, downregulation of apoptotic pathways, overexpression of extracellular matrix proteins, and VEGF induced by pseudoislet formation and 3D-culture. Co-culture with endothelial cells created a natural cellular niche with enhanced insulin secretion after glucose stimulation. Survival and function of pseudoislets after explantation and extensive scaffold vascularization of both hydrogel and heparinized polycaprolactone were demonstrated in vivo. Computer simulations of oxygen, glucose and insulin flows were used to evaluate scaffold architectures and Langerhans islets at a future perivascular transplantation site.
Item Description:Gesehen am 02.06.2022
Physical Description:Online Resource
ISSN:2041-7314
DOI:10.1177/20417314221091033