An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications

Abstract A clinical implementation of cell-based bone regeneration in combination with scaffold materials requires the development of efficient, controlled and reproducible seeding procedures and a tailor-made bioreactor design. A perfusion system for efficient, homogeneous, and rapid seeding with h...

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Autores principales: Nadja Engel, Carsten Fechner, Annika Voges, Robert Ott, Jan Stenzel, Stefan Siewert, Carina Bergner, Valeria Khaimov, Jan Liese, Klaus-Peter Schmitz, Bernd Joachim Krause, Bernhard Frerich
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:035a8910773f4f7a95dcd461eca70e5a2021-11-21T12:21:03ZAn optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications10.1038/s41598-021-01516-82045-2322https://doaj.org/article/035a8910773f4f7a95dcd461eca70e5a2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01516-8https://doaj.org/toc/2045-2322Abstract A clinical implementation of cell-based bone regeneration in combination with scaffold materials requires the development of efficient, controlled and reproducible seeding procedures and a tailor-made bioreactor design. A perfusion system for efficient, homogeneous, and rapid seeding with human adipogenic stem cells in bone substitute scaffolds was designed. Variants concerning medium inlet and outlet port geometry, i.e. cylindrical or conical diffuser, cell concentration, perfusion mode and perfusion rates were simulated in silico. Cell distribution during perfusion was monitored by dynamic [18F]FDG micro-PET/CT and validated by laser scanning microscopy with three-dimensional image reconstruction. By iterative feedback of the in silico and in vitro experiments, the homogeneity of cell distribution throughout the scaffold was optimized with adjustment of flow rates, cell density and perfusion properties. Finally, a bioreactor with a conical diffusor geometry was developed, that allows a homogeneous cell seeding (hoover coefficient: 0.24) in less than 60 min with an oscillating perfusion mode. During this short period of time, the cells initially adhere within the entire scaffold and stay viable. After two weeks, the formation of several cell layers was observed, which was associated with an osteogenic differentiation process. This newly designed bioreactor may be considered as a prototype for chairside application.Nadja EngelCarsten FechnerAnnika VogesRobert OttJan StenzelStefan SiewertCarina BergnerValeria KhaimovJan LieseKlaus-Peter SchmitzBernd Joachim KrauseBernhard FrerichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Nadja Engel
Carsten Fechner
Annika Voges
Robert Ott
Jan Stenzel
Stefan Siewert
Carina Bergner
Valeria Khaimov
Jan Liese
Klaus-Peter Schmitz
Bernd Joachim Krause
Bernhard Frerich
An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications
description Abstract A clinical implementation of cell-based bone regeneration in combination with scaffold materials requires the development of efficient, controlled and reproducible seeding procedures and a tailor-made bioreactor design. A perfusion system for efficient, homogeneous, and rapid seeding with human adipogenic stem cells in bone substitute scaffolds was designed. Variants concerning medium inlet and outlet port geometry, i.e. cylindrical or conical diffuser, cell concentration, perfusion mode and perfusion rates were simulated in silico. Cell distribution during perfusion was monitored by dynamic [18F]FDG micro-PET/CT and validated by laser scanning microscopy with three-dimensional image reconstruction. By iterative feedback of the in silico and in vitro experiments, the homogeneity of cell distribution throughout the scaffold was optimized with adjustment of flow rates, cell density and perfusion properties. Finally, a bioreactor with a conical diffusor geometry was developed, that allows a homogeneous cell seeding (hoover coefficient: 0.24) in less than 60 min with an oscillating perfusion mode. During this short period of time, the cells initially adhere within the entire scaffold and stay viable. After two weeks, the formation of several cell layers was observed, which was associated with an osteogenic differentiation process. This newly designed bioreactor may be considered as a prototype for chairside application.
format article
author Nadja Engel
Carsten Fechner
Annika Voges
Robert Ott
Jan Stenzel
Stefan Siewert
Carina Bergner
Valeria Khaimov
Jan Liese
Klaus-Peter Schmitz
Bernd Joachim Krause
Bernhard Frerich
author_facet Nadja Engel
Carsten Fechner
Annika Voges
Robert Ott
Jan Stenzel
Stefan Siewert
Carina Bergner
Valeria Khaimov
Jan Liese
Klaus-Peter Schmitz
Bernd Joachim Krause
Bernhard Frerich
author_sort Nadja Engel
title An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications
title_short An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications
title_full An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications
title_fullStr An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications
title_full_unstemmed An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications
title_sort optimized 3d-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/035a8910773f4f7a95dcd461eca70e5a
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