Characterization of the mechanical properties of the native mitral valve leaflets at physiological strain rates is a critical step in improving our understanding of MV function and providing experimental data for dynamic constitutive models. We explored, for the first time, the effects of strain rate (from quasi-static to physiologic) on the biaxial mechanical properties of the native mitral valve anterior leaflet (MVAL). A novel high-speed biaxial testing device was developed, capable of achieving in vitro strain rates reported for the MVAL (Sacks et al., Ann. Biomed. Eng. 30(10):1280-1290, 2002). Porcine MVAL specimens were loaded to physiological load levels with cycle periods of 15, 1, 0.5, 0.1, and 0.05 s. The resulting loading stress-strain responses were found to be remarkably independent of strain rate. The hysteresis, defined as the fraction of the membrane strain energy between the loading and unloading curves tension-areal stretch curves, was low (approximately 12%) and did not vary with strain rate. The results of the present work indicated that MVAL tissues exhibit complete strain rate insensitivity at and below physiological strain rates under physiological loading conditions. These novel results suggest that experimental tests utilizing quasi-static strain rates are appropriate for constitutive model development for mitral valve tissues. The mechanisms underlying this quasi-elastic behavior are as yet unknown, but are likely an important functional aspect of native mitral valve tissues and clearly warrant further study.

We have recently demonstrated that the mitral valve anterior leaflet (MVAL) exhibited minimal hysteresis, no strain rate sensitivity, stress relaxation but not creep (Grashow et al., 2006, Ann Biomed Eng., 34(2), pp. 315-325; Grashow et al., 2006, Ann Biomed. Eng., 34(10), pp. 1509-1518). However, the underlying structural basis for this unique quasi-elastic mechanical behavior is presently unknown. As collagen is the major structural component of the MVAL, we investigated the relation between collagen fibril kinematics (rotation and stretch) and tissue-level mechanical properties in the MVAL under biaxial loading using small angle X-ray scattering. A novel device was developed and utilized to perform simultaneous measurements of tissue level forces and strain under a planar biaxial loading state. Collagen fibril D-period strain (epsilonD) and the fibrillar angular distribution were measured under equibiaxial tension, creep, and stress relaxation to a peak tension of 90 N/m. Results indicated that, under equibiaxial tension, collagen fibril straining did not initiate until the end of the nonlinear region of the tissue-level stress-strain curve. At higher tissue tension levels, epsilonD increased linearly with increasing tension. Changes in the angular distribution of the collagen fibrils mainly occurred in the tissue toe region. Using epsilonD, the tangent modulus of collagen fibrils was estimated to be 95.5+/-25.5 MPa, which was approximately 27 times higher than the tissue tensile tangent modulus of 3.58+/-1.83 MPa. In creep tests performed at 90 N/m equibiaxial tension for 60 min, both tissue strain and epsilonD remained constant with no observable changes over the test length. In contrast, in stress relaxation tests performed for 90 min epsilonD was found to rapidly decrease in the first 10 min followed by a slower decay rate for the remainder of the test. Using a single exponential model, the time constant for the reduction in collagen fibril strain was 8.3 min, which was smaller than the tissue-level stress relaxation time constants of 22.0 and 16.9 min in the circumferential and radial directions, respectively. Moreover, there was no change in the fibril angular distribution under both creep and stress relaxation over the test period. Our results suggest that (1) the MVAL collagen fibrils do not exhibit intrinsic viscoelastic behavior, (2) tissue relaxation results from the removal of stress from the fibrils, possibly by a slipping mechanism modulated by noncollagenous components (e.g. proteoglycans), and (3) the lack of creep but the occurrence of stress relaxation suggests a "load-locking" behavior under maintained loading conditions. These unique mechanical characteristics are likely necessary for normal valvular function.

A fundamental assumption in mitral valve (MV) therapies is that a repaired or replaced valve should mimic the functionality of the native valve as closely as possible. Thus, improvements in valvular treatments are dependent on the establishment of a complete understanding of the function and mechanical properties of the native normal MV. In a recent study [Grashow et al. ABME 34(2), 2006] we demonstrated that the planar biaxial stress-strain relationship of the MV anterior leaflet (MVAL) exhibited minimal hysteresis and a stress-strain response independent of strain rate, suggesting that MVAL could be modeled as a "quasi-elastic" material. The objective of our current study was to expand these results to provide a more complete picture of the time-dependent mechanical properties of the MVAL. To accomplish this, biaxial stress-relaxation and creep studies were performed on porcine MVAL specimens. Our primary finding was that while the MVAL leaflet exhibited significant stress relaxation, it exhibited negligible creep over the 3-h test. These results furthered our assertion that the MVAL functionally behaves not as a linear or non-linear viscoelastic material, but as an anisotropic quasi-elastic material. These results appear to be unique in the soft tissue literature; suggesting that valvular tissues are unequalled in their ability to withstand significant loading without time-dependent material effects. Moreover, insight into these specialized characteristics can help guide and inform efforts directed toward surgical repair and engineered valvular tissue replacements.