Computational modeling to predict the micromechanical environment in tissue engineering scaffolds

Cell fate in tissue engineering (TE) strategies is paramount to regenerate healthy, functional organs. The mechanical loads experienced by cells play an important role in cell fate. However, in TE scaffolds with a cell-laden hydrogel matrix, it is prohibitively complex to prescribe and measure this cellular micromechanical environment (CME). Accordingly, this study aimed to develop a finite element (FE) model of a TE scaffold unit cell that can be subsequently implemented to predict the CME and cell fates under prescribed loading. The compressible hyperelastic mechanics of a fibrin hydrogel were characterized by fitting unconfined compression and confined compression experimental data. This material model was implemented in a unit cell FE model of a TE scaffold. The FE mesh and boundary conditions were evaluated with respect to the mechanical response of a region of interest (ROI). A compressible second-order reduced polynomial hyperelastic model gave the best fit to the experimental data (C₁₀ = 1.72 × 10^-4, C₂₀ = 3.83 × 10^-4, D₁ = 3.41, D₂ = 8.06 × 10^-2). A mesh with seed sizes of 40 µm and 60 µm in the ROI and non-ROI regions, respectively, yielded a converged model in 54 min. The in-plane boundary conditions demonstrated minimal influence on ROI mechanics for a 2-by-2 unit cell. However, the out-of-plane boundary conditions did exhibit an appreciable influence on ROI mechanics for a two bilayer unit cell. Overall, the developed unit cell model facilitates the modeling of the mechanical state of a cell-laden hydrogel within a TE scaffold under prescribed loading. This model will be utilized to characterize the CME in future studies, and 3D micromechanical criteria may be applied to predict cell fate in these scaffolds.