Planar Biaxial Mechanical Behavior of Bioartificial Tissues Possessing Prescribed Fiber Alignment

Abstract

Though it is widely accepted that fiber alignment has a great influence on the mechanical anisotropy of tissues, a systematic study of the influence of fiber alignment on the macroscopic mechanical behavior by native tissues is precluded due to their predefined microstructure and heterogeneity. Such a study is possible using collagen-based bioartificial tissues that allow for alignment to be prescribed during their fabrication. To generate a systemic variation of strength of fiber alignment, we made cruciform tissue constructs in Teflon molds that had arms of different aspect ratios. We implemented our anisotropic biphasic theory of tissue-equivalent mechanics to simulate the compaction by finite element analysis. Prior to tensile testing, the construct geometry was standardized by cutting test samples with a 1:1 cruciform punch after releasing constructs from the molds. Planar biaxial testing was performed on these samples, after stretching them to their in-mold dimensions to recover in-mold alignment, to observe the macroscopic mechanical response with simultaneous fiber alignment imaging using a polarimetry system. We found that the strength of fiber alignment of the samples prior to release from the molds linearly increased with anisotropy of the mold, and the modulus ratio (modulus in fiber-direction) / (modulus in normal-direction) was greater as the initial strength of fiber alignment increased, that is, as the aspect ratio increased. We also found that the fiber alignment strength and modulus ratio increased in a hyperbolic fashion with stretching for a sample of given aspect ratio.

Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels

“…For the mold geometry studied, cell compaction produced strong alignment along the vertical and horizontal arms of the cruciform and gave the central region slightly more alignment in the horizontal direction because of the wider horizontal arms used (16). During mechanical testing, real-time fiber reorganization in the cruciform was assessed by monitoring changes in fiber direction () and strength of fiber alignment (␦*) with polarimetric fiber alignment imaging (PFAI).…”

“…The mold geometry consisted of a vertical channel 4 mm wide and a horizontal channel 8 mm wide. This configuration produces strong alignment in the arms and produces slightly more horizontal alignment in the center (16). The cruciform was cultured for 4 days to allow compaction, which stiffens and aligns the gel, without allowing significant remodeling to occur.…”

“…Our group is developing multiscale modeling techniques to understand how the complex mechanical interactions that arise within the ECM microstructure are integrated into the mechanical response of the whole tissue, particularly in engineered tissues (13)(14)(15). In our experiments, we mechanically test cross-shaped, cell-compacted collagen gels (cruciforms) (16) while simultaneously imaging local collagen fiber network restructuring (17). An image-based multiscale computational model is then constructed that must match both the macroscopic mechanical response of the cruciform and the microscopic rearrangements of the ECM fiber network that occur during loading.…”

Simulated remodeling of loaded collagen networks via strain-dependent enzymatic degradation and constant-rate fiber growth

“…The cruciform had an arm width ratio of 1:2, with the sample grip in axis 1 measuring 4.0 mm on its edge, and the sample grip in axis 2 measuring 8.0 mm. This geometry was chosen to be consistent with previous experimental and computational studies (Sander et al, 2009b; Jhun et al, 2009). The mesh discretization was tested against a refined 1172-element uniaxial mesh and resulted in a mean grip-to-grip Green strain difference of only 0.19% versus the 290-element mesh over a 1000-second fixed force uniaxial hold with decay, ensuring that the chosen mesh discretization was sufficiently refined for the present study.…”

Swelling of Collagen-Hyaluronic Acid Co-Gels: An In Vitro Residual Stress Model

“…For example, the relationship between microscopic fiber alignment and macroscopic mechanical properties has been studied extensively in this model system 16, 36, 22, 20, 26 . Collagen gels, often in conjunction with other biopolymers, have served for a long time as the basis for many engineered tissues 39 .…”