Porcine bioprosthetic heart valves (PBHV) continue to fail from calcification and mechanical damage. We have demonstrated for PBHV that cyclic fatigue induces loss of radial compliance, tensile strength, and flexural rigidity. Clinically, about 85 percent of all PBHV fail with tearing, and some fail with little or no calcification. These and other studies demonstrate that while not a strict prerequisite for calcification, maintaining tissue structural integrity is a prime factor in inhibiting PBHV calcification and extending durability. Our long-term goal is the development of rigorous engineering principals for improving PBHV, based on a thorough understanding of tissue-and organ-level biomechanics. During the cardiac cycle cusps undergo large flexural displacements, subjecting the layers to alternating tensile and compressive stresses. Cuspal flexural rigidity, and hence the stresses during flexure, are substantially increased by chemical treatment. Since PBHV are fibrous composite materials, it is likely that they are very susceptible to compressive stress induced damage. We hypothesize that a major mechanism of PBHV failure is structural damage independent of calcification, resulting from high compressive stresses present in the chemically treated tissue extracellular matrix (ECM) during cuspal flexure. An in-depth understanding of the fatigue life behavior of the chemically treated porcine aortic valve cusp independent of PBHV design is a critical first step towards the development of novel chemical treatments that seek to mitigate the effects of structural damage. This will ultimately aid in the rational development, as opposed to the current ad-hoc approach, of novel chemically modified collagenous biomaterials for more durable PBHV. We will test our hypothesis with the following specific aims: 1. Determine how chemical treatment alters cuspal layer micromechanics. 2. Quantify PBHV cuspal deformation during the cardiac cycle. 3. Determine how long-term cyclic fatigue alters PBHV later structure and mechanical properties.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063026-03
Application #
6629028
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Lundberg, Martha
Project Start
2001-02-15
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
3
Fiscal Year
2003
Total Cost
$172,905
Indirect Cost
Name
University of Pittsburgh
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Rego, Bruno V; Sacks, Michael S (2017) A functionally graded material model for the transmural stress distribution of the aortic valve leaflet. J Biomech 54:88-95
Soares, Joao S; Feaver, Kristen R; Zhang, Will et al. (2016) Biomechanical Behavior of Bioprosthetic Heart Valve Heterograft Tissues: Characterization, Simulation, and Performance. Cardiovasc Eng Technol 7:309-351
Zhang, Will; Feng, Yuan; Lee, Chung-Hao et al. (2015) A generalized method for the analysis of planar biaxial mechanical data using tethered testing configurations. J Biomech Eng 137:064501
Tam, Hobey; Zhang, Will; Feaver, Kristen R et al. (2015) A novel crosslinking method for improved tear resistance and biocompatibility of tissue based biomaterials. Biomaterials 66:83-91
D'Amore, Antonio; Amoroso, Nicholas; Gottardi, Riccardo et al. (2014) From single fiber to macro-level mechanics: A structural finite-element model for elastomeric fibrous biomaterials. J Mech Behav Biomed Mater 39:146-61
Buchanan, Rachel M; Sacks, Michael S (2014) Interlayer micromechanics of the aortic heart valve leaflet. Biomech Model Mechanobiol 13:813-26
Eckert, Chad E; Fan, Rong; Mikulis, Brandon et al. (2013) On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet. Acta Biomater 9:4653-60
Sugimoto, Hiroatsu; Sacks, Michael S (2013) Effects of Leaflet Stiffness on In Vitro Dynamic Bioprosthetic Heart Valve Leaflet Shape. Cardiovasc Eng Technol 4:2-15
Mirnajafi, Ali; Zubiate, Brett; Sacks, Michael S (2010) Effects of cyclic flexural fatigue on porcine bioprosthetic heart valve heterograft biomaterials. J Biomed Mater Res A 94:205-13
Sacks, Michael S; David Merryman, W; Schmidt, David E (2009) On the biomechanics of heart valve function. J Biomech 42:1804-24

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