title: Predicting cell viability within tissue scaffolds under equiaxial strain: multi-scale finite element model of collagen-cardiomyocytes constructs.
abstract: Successful tissue engineering and regenerative therapy necessitate having extensive knowledge about mechanical milieu in engineered tissues and the resident cells. In this study, we have merged two powerful analysis tools, namely finite element analysis and stochastic analysis, to understand the mechanical strain within the tissue scaffold and residing cells and to predict the cell viability upon applying mechanical strains. A continuum-based multi-length scale finite element model (FEM) was created to simulate the physiologically relevant equiaxial strain exposure on cell-embedded tissue scaffold and to calculate strain transferred to the tissue scaffold (macro-scale) and residing cells (micro-scale) upon various equiaxial strains. The data from FEM were used to predict cell viability under various equiaxial strain magnitudes using stochastic damage criterion analysis. The model validation was conducted through mechanically straining the cardiomyocyte-encapsulated collagen constructs using a custom-built mechanical loading platform (EQUicycler). FEM quantified the strain gradients over the radial and longitudinal direction of the scaffolds and the cells residing in different areas of interest. With the use of the experimental viability data, stochastic damage criterion, and the average cellular strains obtained from multi-length scale models, cellular viability was predicted and successfully validated. This methodology can provide a great tool to characterize the mechanical stimulation of bioreactors used in tissue engineering applications in providing quantification of mechanical strain and predicting cellular viability variations due to applied mechanical strain.
authors.affiliation: Department of Bioengineering, University of Toledo, Toledo, OH, USA.
authors.forename: Mostafa
authors.identifier: http://orcid.org/0000-0001-9388-8149
authors.initials: M
authors.lastname: Elsaadany
authors.affiliation: Department of Mechanical Engineering, The College of New Jersey, Ewing, NJ, USA.
authors.forename: Karen Chang
authors.identifier: http://orcid.org/0000-0003-2223-8805
authors.initials: KC
authors.lastname: Yan
authors.affiliation: Department of Bioengineering, University of Toledo, Toledo, OH, USA. Eda-yildirimayan@utoledo.edu.|Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH, USA. Eda-yildirimayan@utoledo.edu.
authors.forename: Eda
authors.identifier: http://orcid.org/0000-0003-3275-167X
authors.initials: E
authors.lastname: Yildirim-Ayan
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D003094:Collagen / Q000378:metabolism*; D020342:Finite Element Analysis; D006801:Humans; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015203:Reproducibility of Results; D013314:Stress, Mechanical; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D003094:Collagen
keywords: 3D tissue scaffold; Biomechanics; Cardiomyocytes; Cell damage; Cell viability prediction; Collagen; Computational mechanics; Equiaxial strain; Finite element analysis; Mechanical strain; Predictive multi-length scale modeling; Stochastic analysis; Tissue engineering