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: 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, Hannes G Kenngott
Format: Article
Language:English
Published: SAGE Publishing 2022-04-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/20417314221091033
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author 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
Hannes G Kenngott
author_facet 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
Hannes G Kenngott
author_sort Gabriel A Salg
collection DOAJ
description 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.
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spelling doaj.art-586238002f114a4689c233790fa2608e2022-12-22T02:57:43ZengSAGE PublishingJournal of Tissue Engineering2041-73142022-04-011310.1177/20417314221091033Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissueGabriel A Salg0Eric Poisel1Matthias Neulinger-Munoz2Jamina Gerhardus3Daniel Cebulla4Catrin Bludszuweit-Philipp5Vitor Vieira6Felix Nickel7Ingrid Herr8Andreas Blaeser9Nathalia A Giese10Thilo Hackert11Hannes G Kenngott12Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Dermatology and Allergy, University Hospital LMU Munich, Munich, GermanyTechnical University of Darmstadt, Institute for BioMedical Printing Technology, Darmstadt, GermanyASD Advanced Simulation and Design GmbH, Rostock, GermanyASD Advanced Simulation and Design GmbH, Rostock, GermanyINOVA DE GmbH, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, GermanyTechnical University of Darmstadt, Institute for BioMedical Printing Technology, Darmstadt, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, GermanyThree-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.https://doi.org/10.1177/20417314221091033
spellingShingle 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
Hannes G Kenngott
Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue
Journal of Tissue Engineering
title Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue
title_full Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue
title_fullStr Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue
title_full_unstemmed Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue
title_short Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue
title_sort toward 3d bioprinting of an endocrine pancreas a building block concept for bioartificial insulin secreting tissue
url https://doi.org/10.1177/20417314221091033
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