(M-494) Viscoelastic characterization of right ventricle biomimetic polyester urethane urea scaffolds

Introduction:: Tissue engineered bioscaffolds are widely used to investigate the pathogenesis and regenerative treatment of heart diseases. Our group has recently developed a tissue engineered platform to fabricate anisotropic polyester urethane urea (PEUU) scaffolds that mimic the elastic behavior of healthy and diseased right ventricles (RV). However, the myocardial wall is viscoelastic in nature, exhibiting both elastic and viscous resistance during the deformation of the tissue. The increase in myocardium viscoelasticity has been found to impair systolic and diastolic function in failing ventricles, including the RV. While the biaxial elastic behavior of the PEUU scaffolds has been reported, it is unclear whether these scaffolds are viscoelastic and how similar their viscoelastic behavior is compared to that of native RVs. The aims of this work are to characterize the anisotropic viscoelastic behavior of PEUU scaffolds and compare it to the viscoelasticity of rat RV tissues in healthy and diseased conditions.


Materials and Methods:: The fabrication of PEUU scaffolds was described previously. Briefly, two groups of PEUU scaffolds were electrospun to exhibit distinct Young’s modulus and degree of fiber alignment that mimic normal (soft&anisotropic; soft) and failing (stiff&anisotropic; stiff) RVs reported in literature. To measure the viscoelastic behavior of scaffolds, equibiaxial stress relaxation testing was performed after at least 24 hr of soaking in 1x PBS and at room temperature for each group (n=7 per group). The main fiber direction was used as the longitudinal direction and the cross-fiber direction was the circumferential direction. Prior to data acquisition, cyclic equibiaxial stretches were performed at 1 Hz, with a maximum strain level of 20% to precondition the scaffolds. The scaffolds then underwent stress relaxation testing with an input strain of 15%, using different ramp speeds representing quasi-static stretch rate (0.1 Hz) and physiological stretch rates of the human and rodent species (1 Hz and 5 Hz, respectively). Only the data from the ramping speed at rodent heart stretch rate is presented. The native RV viscoelasticity in healthy and failing (induced by monocrotaline (MCT) treatment) condition was obtained from a separate study using the same testing protocol and then compared to the scaffold groups. From the stress relaxation data, elastic and viscous properties are calculated by relaxation modulus and normalized stress as previously reported. Additionally, dissipated energy (W_d) (viscosity), stored energy (W_s) (elasticity), and the ratio of them (V/E) were derived as illustrated in Figure 1.


Results, Conclusions, and Discussions:: First, we examined the anisotropic viscoelastic properties of PEUU scaffolds. Significant viscoelastic relaxation was observed in all samples. In addition, we compared the elastic and viscous behaviors using stored energy and dissipated energy and observed marked differences between the fiber and cross-fiber directions at all periods of the relaxation (Figure 2). The V/E ratio was also higher in the fiber than cross-fiber direction (p< 0.05), but it did not differ between groups (soft vs. stiff) (data not shown). Furthermore, the comparisons between scaffold groups showed that the soft group tended to have lower relaxation modulus and had smaller normalized stress than the stiff group (Figure 3). Similar findings were observed in the longitudinal direction (data not shown). Finally, we compared the soft scaffold with the healthy RVs (CTL) and compared the stiff scaffold with the failing RVs (MCT). We found that the relaxation moduli of the scaffolds were similar to those of the native tissues in both directions. The normalized stress was similar between the stiff scaffold and diseased tissue, but it was significantly lower in the soft scaffold than the healthy tissue in the circumferential direction (Figure 4).

Therefore, our data showed that the PEUU scaffolds exhibit strong anisotropy for both elasticity and viscosity, with a stronger viscoelasticity found in the fiber direction. The larger V/E ratio in the fiber direction of the PEUU scaffolds suggests that the dissipated energy overweighs the stored energy in this direction. Besides, the soft scaffold tended to have smaller relaxation modulus and had lower normalized stress than the stiff scaffold, indicating a softer and more viscous material. Our data also showed that the viscoelasticity of these scaffolds was similar to the native tissues except for a larger viscosity in the soft scaffolds than the healthy RVs in the circumferential direction. Thus, improvement in the viscous behavior of soft scaffolds is needed to better capture the viscoelastic behavior of the healthy RV free wall. With the increasing evidence of the roles of viscoelastic matrix on cell behavior, more attention should be paid to the viscoelastic behavior of bioscaffolds in tissue engineering.


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