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Shell engineering in soft alginate-based capsules for culturing liver tumoroids
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  • Xuan Peng,
  • Zeljko Janicjievic,
  • Sandy Lemm,
  • Markus Laube,
  • Jens Pietzsch,
  • Michael Bachmann,
  • Larysa Baraban
Xuan Peng
Helmholtz Centre Dresden-Rossendorf Institute of Radiopharmaceutical Cancer Research

Corresponding Author:x.peng@hzde.de

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Zeljko Janicjievic
Helmholtz Centre Dresden-Rossendorf Institute of Radiopharmaceutical Cancer Research
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Sandy Lemm
Helmholtz Centre Dresden-Rossendorf Institute of Radiopharmaceutical Cancer Research
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Markus Laube
Helmholtz Centre Dresden-Rossendorf Institute of Radiopharmaceutical Cancer Research
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Jens Pietzsch
Helmholtz Centre Dresden-Rossendorf Institute of Radiopharmaceutical Cancer Research
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Michael Bachmann
Helmholtz Centre Dresden-Rossendorf Institute of Radiopharmaceutical Cancer Research
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Larysa Baraban
Helmholtz Centre Dresden-Rossendorf Institute of Radiopharmaceutical Cancer Research
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Abstract

Functional interaction between cancer cells and the surrounding microenvironment is still not sufficiently understood, which motivates the tremendous interest for the development of numerous in vitro and in vivo tumor models. Diverse parameters, e.g., transport of nutrients and metabolites, availability of space in the confinement, interaction with scaffolds, etc. make an impact on the size, shape, and metabolism of the tumoroids. Herein, we demonstrate the fluidics-based low-cost methodology to reproducibly generate the alginate and alginate-chitosan microcapsules and apply it to grow human hepatoma (HepG2) tumoroids of different dimensions and geometries. Focusing specifically on the composition and thickness of the hydrogel shell, permeability of the microcapsules is selectively tuned. The diffusion of the selected benchmark molecules through the shell has been systematically investigated using both, experiments and simulations, which is essential to ensure efficient mass transfer of small molecules and prevent large substances from reaching the encapsulated cells. Depending on available space, phenotypically different 3D cell assemblies have been observed inside the capsules, varying in the tightness of cell aggregations and their shapes. Metabolic activity of tumoroids in microcapsules was confirmed by tracking the turnover of testosterone to androstenedione with chromatography studies in a metabolic assay. Because of the high reproducibility, compartmentalization, and facile tuning of the shell thickness and permeability, our system is not only a great platform for the formation of cancer tumoroids, but also a promising tool for the design and engineering of other cells.
15 Jul 2022Submitted to Biotechnology Journal
18 Jul 2022Submission Checks Completed
18 Jul 2022Assigned to Editor
27 Jul 2022Reviewer(s) Assigned
06 Sep 2022Editorial Decision: Revise Major
15 Nov 20221st Revision Received
16 Nov 2022Submission Checks Completed
16 Nov 2022Assigned to Editor
23 Nov 2022Reviewer(s) Assigned
23 Feb 2023Review(s) Completed, Editorial Evaluation Pending
09 Mar 2023Editorial Decision: Accept