Effects of cyclic flexural fatigue on porcine bioprosthetic heart valve heterograft biomaterials

Abstract

Although bioprosthetic heart valves (BHV) remain the primary treatment modality for adult heart valve replacement, continued problems with durability remain. Several studies have implicated flexure as a major damage mode in porcine-derived heterograft biomaterials used in BHV fabrication. Although conventional accelerated wear testing can provide valuable insights into BHV damage phenomena, the constituent tissues are subjected to complex, time-varying deformation modes (i.e., tension and flexure) that do not allow for the control of the amount, direction, and location of flexure. Thus, in this study, customized fatigue testing devices were developed to subject circumferentially oriented porcine BHV tissue strips to controlled cyclic flexural loading. By using this approach, we were able to study layer-specific structural damage induced by cyclic flexural tensile and compressive stresses alone. Cycle levels of 10 x 10(6), 25 x 10(6), and 50 x 10(6) were used, with resulting changes in flexural stiffness and collagen structure assessed. Results indicated that flexural rigidity was markedly reduced after only 10 x 10(6) cycles, and progressively decayed at a lower rate with cycle number thereafter. Moreover, the against-curvature fatigue direction induced the most damage, suggesting that the ventricularis and fibrosa layers have low resistance to cyclic flexural compressive and tensile loads, respectively. The histological analyses indicated progressive collagen fiber delamination as early as 10 x 10(6) cycles but otherwise no change in gross collagen orientation. Our results underscore that porcine-derived heterograft biomaterials are very sensitive to flexural fatigue, with delamination of the tissue layers the primary underlying mechanism. This appears to be in contrast to pericardial BHV, wherein high tensile stresses are considered to be the major cause of structural failure. These findings point toward the need for the development of chemical fixation technologies that minimize flexure-induced damage to extend porcine heterograft biomaterial durability. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Fig. 1

(a) The region of the leaflet from which the specimens were dissected, (b) a schematic highlighting how the leaflet layers are loaded under flexure.

Fig. 2

(a) A photo of the FA and FW fatigue devices and the overall experimental setup, and (b) enlarged schematic of the flexing mechanism.

Fig. 3

(a) Sequence of images representing a complete cycle of motion, (b) enlarged images depicting the extreme curvatures with numerical approximations of the sample shape superimposed. Here, the numbers indicate the marker number, d the pivot distance, and h the maximum specimen displacement. Instantaneous curvatures were determined by fitting the marker positions (see text for details).

Fig. 4

(a) Representative M/I-Δκ response for the BHV porcine tissues, highlighting the directional differences. The directional differences were consistent in all specimens, with approximately a 2:1 ratio between the AC and WC directions, respectively (b), clearly underscoring the effects of varying layer mechanical behaviors in the unicycle state. *-statistically significant (p<0.05) from the AC value.

Fig. 5

The flexural rigidity EI vs. cycle number for both FA and FW groups tested in both AC and WC directions. Both groups for both directions demonstrated substantial drop in EI with increasing cycle number, with the greatest changes occurring in the first 10×10⁶ cycles. Normalized EI reductions indicated that the AC direction, regardless of the direction of applied cyclic flexure, experienced the greatest decrease in value. *-statistically significant (p<0.05) from the corresponding AC value.

Fig. 6

The results of SALS analysis of specimen from both FA and FW group scanned after each loading increment, indicating little change in overall collagen fiber alignment.

Fig. 7

Results of histology of specimen of FA group analyzed after each loading cycle showing the complete cross section of the specimens. Note that progressive delamination occurred with increasing cycle number.