Stress Analysis-Driven Design of Bilayered Scaffolds for Tissue Engineered Vascular Grafts

[+] Author and Article Information
Jason M Szafron

Department of Biomedical Engineering, Yale University, New Haven, CT 06520

Christopher Breuer

Tissue Engineering Program, Nationwide Children's Hospital, Columbus, OH 43215

Yadong Wang

Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853

Jay Humphrey

Fellow ASME, Department of Biomedical Engineering, Yale University, New Haven, CT 06520

1Corresponding author.

ASME doi:10.1115/1.4037856 History: Received April 11, 2017; Revised August 11, 2017


Continuing advances in the fabrication of scaffolds for tissue engineered vascular grafts is greatly expanding the scope of potential designs. Increasing recognition of the importance of local biomechanical cues for cell-mediated neotissue formation, neovessel growth, and subsequent remodeling is similarly influencing the design process. This study examines directly the potential effects of different combinations of key geometric and material properties of polymeric scaffolds on the initial mechanical state of an implanted graft into which cells are seeded or migrate. Toward this end, we developed a bilayered computational model that accounts for layer-specific thickness and stiffness, as well as the potential to be residually stressed during fabrication or to swell during implantation. We found that, for realistic ranges of parameter values, the circumferential stress that would be presented to seeded or infiltrating cells is typically much lower than ideal, often by an order of magnitude. Indeed, accounting for layer-specific intrinsic swelling resulting from hydrophilicity or residual stresses not relieved via annealing revealed potentially large compressive stresses, which could lead to unintended cell phenotypes and associated maladaptive growth or, in extreme cases, graft failure. Metrics of global hemodynamics were also found to be inversely related to markers of a favorable local mechanobiological environment, suggesting a tradeoff in designs that seek mechanical homeostasis at a single scale. These findings highlight the importance of the initial mechanical state in tissue engineering scaffold design and the utility of computational modeling in reducing the experimental search space for future graft development and testing.

Copyright (c) 2017 by ASME
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