Effects of Valve Geometry and Tissue Anisotropy on the Radial Stretch and Coaptation Area of Tissue-Engineered Heart Valves

Abstract

Tissue engineering represents a promising technique to overcome the limitations of the current valve replacements, since it allows for creating living autologous heart valves that have the potential to grow and remodel. However, also this approach still faces a number of challenges. One particular problem is regurgitation, caused by cell-mediated tissue retraction or the mismatch in geometrical and material properties between tissue-engineered heart valves (TEHVs) and their native counterparts. The goal of the present study was to assess the influence of valve geometry and tissue anisotropy on the deformation profile and closed configuration of TEHVs. To achieve this aim, a range of finite element models incorporating different valve shapes was developed, and the constitutive behavior of the tissue was modeled using an established computational framework, where the degree of anisotropy was varied between values representative of TEHVs and native valves. The results of this study suggest that valve geometry and tissue anisotropy are both important to maximize the radial strains and thereby the coaptation area. Additionally, the minimum degree of anisotropy that is required to obtain positive radial strains was shown to depend on the valve shape and the pressure to which the valves are exposed. Exposure to pulmonary diastolic pressure only yielded positive radial strains if the anisotropy was comparable to the native situation, whereas considerably less anisotropy was required if the valves were exposed to aortic diastolic pressure. AbstractTissue engineering represents a promising technique to overcome the limitations of the current valve replacements, since it allows for creating living autologous heart valves that have the potential to grow and remodel. However, also this approach still faces a number of challenges. One particular problem is regurgitation, caused by cell-mediated tissue retraction or the mismatch in geometrical and material properties between tissue-engineered heart valves (TEHVs) and their native counterparts. The goal of the present study was to assess the influence of valve geometry and tissue anisotropy on the deformation profile and closed configuration of TEHVs. To achieve this aim, a range of finite element models incorporating different valve shapes was developed, and the constitutive behavior of the tissue was modeled using an established computational framework, where the degree of anisotropy was varied between values representative of TEHVs and native valves. The results of this study suggest that valve geometry and tissue anisotropy are both important to maximize the radial strains and thereby the coaptation area. Additionally, the minimum degree of anisotropy that is required to obtain positive radial strains was shown to depend on the valve shape and the pressure to which the valves are exposed. Exposure to pulmonary diastolic pressure only yielded positive radial strains if the anisotropy was comparable to the native situation, whereas considerably less anisotropy was ...

A Computational Tool for the Microstructure Optimization of a Polymeric Heart Valve Prosthesis

“…A similar result was also obtained by Loerakker et al [18] with a model of tissue engineered heart valves, where a larger radial and smaller circumferential strain were found with an increased material anisotropy.…”

“…As a consequence of this particular architecture, the leaflet circumferential stiffness is significantly larger than the radial stiffness (about 15 MPa versus 2 MPa [11,15]). Even if the mechanisms underlying this tissue arrangement are not completely understood, it surely influence the valve mechanical behavior and failure mechanism [13,[16][17][18][19][20]. The anisotropic tissue structure allows the valve to open easily due to the low resistance of collagen fibers to bending and increases the material stiffness and strength during valve closure.…”

Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model

“…S1) (32,33). In brief, a relatively large coaptation area was included in the design to address potential retraction phenomena in this region as documented in our previous preclinical studies (15,22) and predicted in a recent computational study (34).…”

“…The initial mechanical behavior of the valves was predicted using computational modeling as described previously (32,33). In short, the valve geometry was described according to Hamid et al (49) and equaled the geometry imposed on the TEHVs via the geometrical constraints described above.…”

Efficient computational simulation of actin stress fiber remodeling

“…For example, in heart valves, circumferentially aligned collagen fibers have been observed (Billiar & Sacks 2000a;Martin & Sun 2012) that transfer the pressure applied on the closed heart valve to the aortic wall (Peskin & McQueen 1994). Furthermore, they reinforce the circumferential direction enabling the stretch in the radial direction for a proper closure of the heart valve (Billiar & Sacks 2000a, 2000bSacks et al 2009;Martin & Sun 2012;Fan et al 2013;Loerakker et al 2013). Next to external loads (Ruberti & Hallab 2005;Bhole et al 2009;Wyatt et al 2009;De Jonge et al 2013), the collagen network is remodeled by contractile forces exerted by the cells along their principal direction, which is determined by the organization of actin stress fibers (Wang et al 2003;Ghibaudo et al 2008;Faust et al 2011).…”