Effects of Scaffold Architecture, Materials, and Loading on Cellular Micromechanical Environment in Tissue Engineering Strategies

In tissue engineering (TE) strategies, cell processes are regulated by mechanical stimuli. Although TE scaffolds have been developed to replicate tissue-level mechanical properties, it is experimentally prohibitive to measure and prescribe the cellular micromechanical environment (CME) generated within these constructs. Accordingly, this study aimed to fill this lack of understanding by modelling the CME in TE scaffolds using the finite element method. A repeating unit of composite fiber scaffold for annulus fibrosus repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The CME was predicted and the corresponding cell phenotypes were predicted based on previously hypothesized criteria. Scaffold multi-axial loading was demonstrated as the most pertinent parameter contributing to the CME criteria being satisfied. Specifically, radial-direction compression with biaxial tension lead to a prediction of regeneration for 66.5% of the cell volumes. Additionally, the architectural scale had a moderate influence on the CME with minimal change in the tissue-level properties of the scaffold. All other scaffold materials and architectures considered had secondary influences on the predicted regeneration by modifying the scaffold loading. By predicting the regeneration potential of different scaffold designs, the developed high-fidelity computational tool described in this study enables for a more comprehensive understanding of the relationship between tissue-level and cell-level mechanics for a broad range of tissue engineering applications.