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Accurately assessing the complex tissue mechanics of cerebral aneurysms (CAs) is critical for elucidating how CAs grow and whether that growth will lead to rupture. The factors that have been implicated in CA progression - blood flow dynamics, immune infiltration, and extracellular matrix remodeling - all occur heterogeneously throughout the CA. Thus, it stands to reason that the mechanical properties of CAs are also spatially heterogeneous. Here, we present a new method for characterizing the mechanical heterogeneity of human CAs using generalized anisotropic inverse mechanics, which uses biaxial stretching experiments and inverse analyses to determine the local Kelvin moduli and principal alignments within the tissue. Using this approach, we find that there is significant mechanical heterogeneity within a single acquired human CA. These results were confirmed using second harmonic generation imaging of the CA's fiber architecture and a correlation was observed. This approach provides a single-step method for determining the complex heterogeneous mechanics of CAs, which has important implications for future identification of metrics that can improve accuracy in prediction risk of rupture., (© 2021 S. Karger AG, Basel.)

Amyloid beta accumulation in neuronal and cerebrovascular tissue is a key precursor to development of Alzheimer's disease and can result in neurodegeneration. While its persistence in Alzheimer's cases is well-studied, amyloid beta's direct effect on vascular function is unclear. Here, we measured the effect of amyloid beta treatment on vascular smooth muscle cell functional contractility and modeled the mechanoadaptive growth and remodeling response to these functional perturbations. We found that the amyloid beta 1-42 isoform induced a reduction in vascular smooth muscle cell mechanical output and reduced response to vasocontractile cues. These data were used to develop a thin-walled constrained mixture arterial model that suggests vessel growth, and remodeling in response to amyloid betamediated alteration of smooth muscle function leads to decreased ability of cerebrovascular vessels to vasodilate. These findings provide a possible explanation for the vascular injury and malfunction often associated with the development of neurodegeneration in Alzheimer's disease.

Vascular disease is a leading cause of death globally and typically manifests chronically due to long-term maladaptive arterial growth and remodeling. To date, there is no in vitro technique for studying vascular function over relevant disease time courses that both mimics in vivo-like tissue structure and provides a simple readout of tissue stress. We aimed to extend tissue viability in our muscular thin film contractility assay by modifying the polydimethylsiloxane (PDMS) substrate with micropatterned genipin, allowing extracellular matrix turnover without cell loss. To achieve this, we developed a microfluidic delivery system to pattern genipin and extracellular matrix proteins on PDMS prior to cell seeding. Tissues constructed using this method showed improved viability and maintenance of in vivo-like lamellar structure. Functional contractility of tissues fabricated on genipin-modified substrates remained consistent throughout two weeks in culture. These results suggest that muscular thin films with genipin-modified PDMS substrates are a viable method for conducting functional studies of arterial growth and remodeling in vascular diseases.

Ascending thoracic aortic aneurysms (ATAA) have a high propensity for dissection, which occurs when the hemodynamic load exceeds the mechanical strength of the aortic media. Despite our recognition of this essential fact, the complex architecture of the media has made a predictive model of medial failure-even in the relatively simple case of the healthy vessel-difficult to achieve. As a first step towards a general model of ATAA failure, we characterized the mechanical behavior of healthy ascending thoracic aorta (ATA) media using uniaxial stretch-to-failure in both circumferential (n = 11) and axial (n = 11) orientations and equibiaxial extensions (n = 9). Both experiments demonstrated anisotropy, with higher tensile strength in the circumferential direction (2510 ± 439.3 kPa) compared to the axial direction (750 ± 102.6 kPa) for the uniaxial tests, and a ratio of 1.44 between the peak circumferential and axial loads in equibiaxial extension. Uniaxial tests for both orientations showed macroscopic tissue failure at a stretch of 1.9. A multiscale computational model, consisting of a realistically aligned interconnected fiber network in parallel with a neo-Hookean solid, was used to describe the data; failure was modeled at the fiber level, with an individual fiber failing when stretched beyond a critical threshold. The best-fit model results were within the 95% confidence intervals for uniaxial and biaxial experiments, including both prefailure and failure, and were consistent with properties of the components of the ATA media.

A mathematical model is presented for growth and remodeling of arteries. The model is a thick-walled tube composed of a constrained mixture of smooth muscle cells, elastin and collagen. Material properties and radial and axial distributions of each constituent are prescribed according to previously published data. The analysis includes stress-dependent growth and contractility of the muscle and turnover of collagen fibers. Simulations were conducted for homeostatic conditions and for the temporal response following sudden hypertension. Numerical pressure-radius relations and opening angles (residual stress) show reasonable agreement with published experimental results. In particular, for realistic material and structural properties, the model predicts measured variations in opening angles along the length of the aorta with reasonable accuracy. These results provide a better understanding of the determinants of residual stress in arteries and could lend insight into the importance of constituent distributions in both natural and tissue-engineered blood vessels.

Epicardial strains were measured in Hamburger-Hamilton stage 11 and 12 embryonic chick hearts (1.6-2.0 days of incubation). These stages include part of the early phase of cardiac looping, as the initially straight heart tube bends and twists to form a curved c-shaped tube. By analyzing the motion of microbeads placed on the myocardial surface, we measured strains near the outer curvature, in the central region, and near the inner curvature of the primitive ventricle. No significant differences in strain were found between stages. Relative to end diastole, all three regions shortened by about 10% during systole in the circumferential direction, and the outer curvature shortened longitudinally by about 5%. In contrast, and unlike strains in older hearts, the inner curvature and central regions elongated by approximately 5-10% in the longitudinal direction during systole. These results are consistent with microstructural data and suggest that the material properties of the outer curvature are relatively isotropic, whereas the properties of the central and inner curvature regions are orthotropic, with contractile stress exerted primarily in the circumferential direction.