Predicting cell fate via intelligent porous microcapsules: A multiphysics computational design framework
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Published on: October 13, 2021
Mahdi Poursaberi1, Guillermo Hauke2, S Jamaleddin Mousavi3
1School of Engineering and Architecture (EINA), University of Zaragoza, Zaragoza, Spain; Aragon Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
Background And Objective:
Controlled and localized release of biochemical signals is essential for regulating cell differentiation, proliferation, apoptosis, and migration during tissue regeneration. Uncontrolled release can cause adverse effects such as inflammation or fibrotic tissue formation, whereas gradual and spatially confined delivery enables precise modulation of cell behavior. Microcapsule-based systems represent a promising strategy to engineer these interactions. In this study, a multiphysics computational design framework is developed to model the coupled mechanisms of molecular diffusion and fundamental cellular processes within extracellular matrices containing porous microcapsules.
Methods:
Molecular release is described using Fick's law, with the membrane modeled as a porous barrier with an effective diffusivity dependent on porosity and thickness. Cell motility is governed by a force-balance formulation, while proliferation and differentiation are regulated by cell deformation and a maturation threshold time dependent on integrated mechanical and chemical stimuli. The model was implemented in a standardized COMSOL and Abaqus environment and validated against Lattice Boltzmann reference data.
Results:
The model showed excellent agreement with reference data for numerical verification of the transport solver. Parametric analyses indicate that increasing membrane porosity accelerates transport, while thickness acts as a resistive barrier. An empirical design equation was derived to act as a computational surrogate, enabling the a priori selection of structural parameters to match specific tissue maturation windows without experimental trial-and-error. Simulations demonstrate that centrally positioned microcapsules generate synergistic chemical-mechanical cues that maximize the cellular response (15 cells) compared to peripheral configurations.
Conclusion:
The proposed framework provides a predictive computational design tool for the rational design of microstructured delivery systems to optimize tissue regeneration.
