Maj Martijn Cox

Mechanical Characterization of Anisotropic Planar Biological Soft Tissues Using Large Indentation: A Computational Feasibility Study

Traditionally, the complex mechanical behavior of planar soft biological tissues is characterized by (multi)axial tensile testing. While uniaxial tests do not provide sufficient information for a full characterization of the material anisotropy, biaxial tensile tests are difficult to perform and tethering effects limit the analyses to a small central portion of the test sample. In both cases, determination of local mechanical properties is not trivial. Local mechanical characterization may be performed by indentation testing. Conventional indentation tests, however, often assume linear elastic and isotropic material properties, and therefore these tests are of limited use in characterizing the nonlinear, anisotropic material behavior typical for planar soft biological tissues. In this study, a spherical indentation experiment assuming large deformations is proposed. A finite element model of the aortic valve leaflet demonstrates that combining force and deformation gradient data, one single indentation test provides sufficient information to characterize the local material behavior. Parameter estimation is used to fit the computational model to simulated experimental data. The aortic valve leaflet is chosen as a typical example. However, the proposed method is expected to apply for the mechanical characterization of planar soft biological materials in general.

The non-linear mechanical properties of soft engineered biological tissues determined by finite spherical indentation.

The mechanical properties of soft biological tissues in general and early stage engineered tissues in particular limit the feasibility of conventional tensile tests for their mechanical characterisation. Furthermore, the most important mode in development of deep tissue injury (DTI) is compression. Therefore, an inverse numerical–experimental approach using a finite spherical indentation test is proposed. To demonstrate the feasibility of the approach indentation tests are applied to bio-artificial muscle (BAM) tissue. BAMs are cultured in vitro with (n = 20) or without (n = 12) myoblast cells to quantify the effect of the cells on the passive transverse mechanical properties. Indentation tests are applied up to 80% of the tissue thickness. A non-linear Neo-Hookean constitutive model is fitted to the experimental results for parameter estimation. BAMs with cells demonstrated both stiffer and more non-linear material behaviour than BAMs without cells.

Poly‐ε‐caprolactone scaffold and reduced in vitro cell culture: beneficial effect on compaction and improved valvular tissue formation

Tissue‐engineered heart valves (TEHVs), based on polyglycolic acid (PGA) scaffolds coated with poly‐4‐hydroxybutyrate (P4HB), have shown promising in vivo results in terms of tissue formation. However, a major drawback of these TEHVs is compaction and retraction of the leaflets, causing regurgitation. To overcome this problem, the aim of this study was to investigate: (a) the use of the slowly degrading poly‐ε‐caprolactone (PCL) scaffold for prolonged mechanical integrity; and (b) the use of lower passage cells for enhanced tissue formation. Passage 3, 5 and 7 (P3, P5 and P7) human and ovine vascular‐derived cells were seeded onto both PGA–P4HB and PCL scaffold strips. After 4 weeks of culture, compaction, tissue formation, mechanical properties and cell phenotypes were compared. TEHVs were cultured to observe retraction of the leaflets in the native‐like geometry. After culture, tissues based on PGA–P4HB scaffold showed 50–60% compaction, while PCL‐based tissues showed compaction of 0–10%. Tissue formation, stiffness and strength were increased with decreasing passage number; however, this did not influence compaction. Ovine PCL‐based tissues did render less strong tissues compared to PGA–P4HB‐based tissues. No differences in cell phenotype between the scaffold materials, species or cell passage numbers were observed. This study shows that PCL scaffolds may serve as alternative scaffold materials for human TEHVs with minimal compaction and without compromising tissue composition and properties, while further optimization of ovine TEHVs is needed. Reducing cell expansion time will result in faster generation of TEHVs, providing more rapid treatment for patients. Copyright

Remodeling of the collagen architecture in cardiovascular tissues

The stimulus functions are assumed to depend on the mechanical loading condition within the tissue, i.e., gi = gi(λi, σi). The stimulus functions are specified such that: (1) for a uniaxial loading condition all fiber directions align with the major loading direction, (2) in case of a biaxial loading condition, the fiber families are situated in between the major directions with the main orientation and dispersity depending on the ratio of g1 and g2, and (3) for an equibiaxial loading condition, the fibers are distributed uniformly in the plane of the major directions v1 and v2. The artery is modeled as a thick-walled cylinder, which is inflated by an internal pressure and stretched longitudinally. The aortic valve is modeled as a leaflet with uniform thickness and is loaded by a transvalvular pressure in the diastolic (i.e., closed) configuration.