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Shell engineering in soft alginate-based capsules for culturing liver spheroids.

Xuan Peng1,2, Željko Janićijević1, Sandy Lemm1,3

  • 1Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.

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|March 21, 2023
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Summary

Researchers developed a low-cost method using fluidics to create tunable microcapsules for growing cancer spheroids. This platform aids in studying cancer cell interactions within the tumor microenvironment.

Keywords:
alginate and alginate-chitosan microcapsuleshuman hepatoma cell line (HepG2)liver spheroidsmicrofluidic droplet generation systempermeability

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Area of Science:

  • Biotechnology
  • Cancer Research
  • Materials Science

Background:

  • Understanding cancer cell and microenvironment interactions is crucial for developing effective cancer therapies.
  • Existing in vitro tumor models face limitations in mimicking the complex tumor microenvironment.
  • Tumoroid growth is influenced by nutrient transport, metabolite exchange, and spatial constraints.

Purpose of the Study:

  • To develop a low-cost, fluidics-based method for generating tunable alginate and alginate-chitosan microcapsules.
  • To investigate the controlled growth of human hepatoma (HepG2) spheroids within these microcapsules.
  • To establish a versatile platform for studying cancer spheroid formation and microenvironment interactions.

Main Methods:

  • Utilized fluidics for reproducible fabrication of alginate and alginate-chitosan microcapsules.
  • Systematically tuned microcapsule permeability by adjusting hydrogel shell composition and thickness.
  • Employed experiments and simulations to analyze the diffusion of benchmark molecules through the microcapsule shells.
  • Assessed spheroid metabolic activity using testosterone to androstenedione turnover assays and chromatography.
  • Observed spheroid morphology and aggregation patterns in response to varying capsule dimensions.

Main Results:

  • Successfully generated alginate and alginate-chitosan microcapsules with tunable permeability.
  • Demonstrated controlled growth of HepG2 spheroids with diverse dimensions and geometries within the microcapsules.
  • Validated efficient mass transfer and selective filtering capabilities of the microcapsule shells.
  • Confirmed metabolic activity of the encapsulated spheroids.
  • Observed phenotypic variations in spheroid morphology and cell aggregation based on available space.

Conclusions:

  • The developed fluidics-based system offers a low-cost and reproducible method for creating tunable microcapsules.
  • This platform facilitates the study of cancer spheroid formation and their interactions with the microenvironment.
  • The ability to tune shell permeability is essential for controlling mass transfer and studying biochemical species.
  • The system provides a promising tool for advancing cancer research and therapeutic development.