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Affordable Oxygen Microscopy-Assisted Biofabrication of Multicellular Spheroids
Published on: April 6, 2022
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A heuristic computational model of basic cellular processes and oxygenation during spheroid-dependent biofabrication.
T J Sego1, U Kasacheuski, D Hauersperger
1Department of Mechanical Engineering, Indiana University-Purdue University at Indianapolis, IN, United States of America.
Biofabrication
|June 16, 2017
Summary
This study introduces a computational model for scaffold-free biofabrication, simulating cell dynamics and metabolism to minimize cell loss in 3D tissue constructs. The model predicts conditions for optimized spheroid fusion and tissue development.
Area of Science:
- Biofabrication
- Biophysics
- Computational Biology
Background:
- Scaffold-free, cell spheroid-only methods are emerging for 3D tissue construct creation.
- Spheroid fusion, driven by energy minimization, is key, but oxygen and metabolite accessibility affect construct properties.
- Metabolism-related cell loss within spheroids is a challenge in biofabrication.
Purpose of the Study:
- To develop a simulation platform for predicting conditions that minimize metabolism-related cell loss in spheroids.
- To model cell behavior and dynamics in response to neighbors and nutrient gradients.
- To enhance scaffold-free bioprinting techniques.
Main Methods:
- A hybrid discrete-continuous heuristic model combining cellular Potts-type approach with field equations.
- Modeling cellular adhesiveness, motility, and interactions with concentration fields (diffusivity, oxygen consumption).
- Incorporating concentration-dependent, stochastic cell dynamics driven by metabolite-dependent cell death.
Main Results:
- The model captured key scaffold-free bioprinting steps: intra-spheroid cell sorting, defect closure, and inter-spheroid fusion.
- Hypoxia-induced cell death at the spheroid core was amplified upon fusion.
- External oxygen supplementation mitigated hypoxia-induced cell death.
Conclusions:
- The developed computational model can optimize scaffold-free biofabrication.
- The model accounts for both cellular dynamics and metabolism in biofabricated constructs.
- Further development of scaffold-free bioprinting can benefit from this predictive modeling approach.

