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Evaluation of the Stress–Growth Hypothesis in Saphenous Vein Perfusion Culture

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Abstract

The great saphenous vein (GSV) has served as a coronary artery bypass graft (CABG) conduit for over 50 years. Despite prevalent use, first-year failure rates remain high compared to arterial autograft options. Amongst other factors, vein graft failure can be attributed to material and mechanical mismatching that lead to apoptosis, inflammation, and intimal-medial hyperplasia. Through the implementation of the continuum mechanical-based theory of “stress-mediated growth and remodeling,” we hypothesize that the mechanical properties of porcine GSV grafts can be favorably tuned for CABG applications prior to implantation using a prolonged but gradual transition from venous to arterial loading conditions in an inflammatory and thrombogenic deficient environment. To test this hypothesis, we used a hemodynamic-mimetic perfusion bioreactor to guide remodeling through stepwise incremental changes in pressure and flow over the course of 21-day cultures. Biaxial mechanical testing of vessels pre- and post-remodeling was performed, with results fit to structurally-motivated constitutive models using non-parametric bootstrapping. The theory of “small-on-large” was used to describe appropriate stiffness moduli, while histology and viability assays confirmed microstructural adaptations and vessel viability. Results suggest that stepwise transition from venous-to-arterial conditions results in a partial restoration of circumferential stretch and circumferential, but not axial, stress through vessel dilation and wall thickening in a primarily outward remodeling process. These remodeled tissues also exhibited decreased mechanical isotropy and circumferential, but not axial, stiffening. In contrast, only increases in axial stiffness were observed using culture under venous perfusion conditions and those tissues experienced moderate intimal resorption.

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Acknowledgments

The authors would like to acknowledge the contributions of Boran Zhou (PhD), Shahd Hasanain (BS), Colton Kostelnik (BS), Laurel Carter (MD) and Nicole Carey (MD) for their technological contributions to the project.

Funding

This work is supported by the National Institutes of Health under Grant Numbers (R21 EB022131, R01HL133662, and P20GM103444).

Conflicts of interest

No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

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Authors and Affiliations

  1. Biomedical Engineering Program, University of South Carolina, Columbia, SC, USA

    David A. Prim, Brooks A. Lane, Tarek Shazly & John F. Eberth

  2. Biomedical Engineering Department, Boston University, Boston, MA, USA

    Jacopo Ferruzzi

  3. Mechanical Engineering Department, University of South Carolina, Columbia, SC, USA

    Tarek Shazly

  4. Cell Biology and Anatomy Department (CBA), SOM, University of South Carolina (USC), Bldg.1, Rm. C-36, Columbia, SC, 29208, USA

    John F. Eberth

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  1. David A. Prim
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Correspondence to John F. Eberth.

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Prim, D.A., Lane, B.A., Ferruzzi, J. et al. Evaluation of the Stress–Growth Hypothesis in Saphenous Vein Perfusion Culture. Ann Biomed Eng 49, 487–501 (2021). https://doi.org/10.1007/s10439-020-02582-1

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