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Information on the layer-specific residual deformations of aortic tissue and how these vary throughout the vessel is important for understanding the regionally-varying aortic functions and pathophysiology, but not so much can be found in the literature. Toward this end, porcine aortas were sectioned into eighteen rings, with one ring from each anatomical position radially cut to obtain the zero-stress state for the intact wall and the other ring dissected into intimal-medial and adventitial layers; these rings were then radially cut to reach the zero-stress state for the intima-media and adventitia. Peripheral variations in internal/external circumferences, thickness, and opening angle of the intact wall and its layers were measured through image analysis at the no-load and zero-stress states. Intact wall and layer circumferences at both states significantly declined along the aorta, as did intact wall and intimal-medial but not adventitial thickness. Adventitia exhibited the greatest opening angles, approaching 180 deg all over the aorta. The opening angles of the intima-media and intact wall were quite similar, with the highest values in the ascending aorta, the lowest at the diaphragm, and increasing subsequently. Bending-related residual stretches were released by radial cutting that were compressive internally and tensile externally, displaying distinct axial variation for the intima-media and intact wall, and non-significant variation for the adventitia. Evidence is provided for the release upon layer separation of compressive stretches in the intima-media and of tensile stretches in the adventitia, whose values were smallest in the descending thoracic aorta and highest near the iliac artery bifurcation.

Detailed estimation of axial residual strains in the human aorta is necessary when performing biomechanical analyses of physiologic functions and pathologic conditions. We recently published such data for autopsied aortas and the present aim was to measure axial residual stretches at different wall depths, along with layer thicknesses on images borrowed from that work. Residual stretches at the external surface and medial-adventitial interface increased along the aorta’s ascending course, decreased along its descending course, and increased from the diaphragm toward the iliac arteries. Residual stretches at the intimal-medial interface and internal surface decreased down the distal one-third of the aorta. A continuous decrease in medial thickness was witnessed along the vessel, whereas intimal and adventitial thickness remained fairly stable. At some axial locations, smaller were the axial residual stretches of the outer than those of the other quadrants, with minor differences in layer-specific thicknesses among quadrants. Adventitial thickness did not vary with age, while the intima and media thickened considerably with different time-courses. The observed intimal thickening solely between young (≤40 yr) and middle-aged subjects (40–60 yr) is consistent with the increased circumferential residual stretches previously established by our group between those subject groups and the minimal further increase in old subjects (≥60 yr). The observed medial thickening between middle-aged and old subjects was accompanied by decreased axial residual stretches that were not seen between young and middle-aged subjects. These observations suggest distinct roles for the intima and media in determining circumferential and axial residual stretches that merit further attention.

Aortic dissection often initiates a few centimeters distal to the coronary ostia in the right lateral wall, with an intimal-medial tear that tends to be transversely directed and occupy half of the aortic circumference, sometimes less, but seldom the entire circumference. To elucidate these clinical observations, tear tests were presently used to determine the layer-specific resistance to tear propagation in ascending thoracic aortic aneurysms, assessing variations over the four circumferential quadrants and two directions. Aneurysmal tissue strips of standardized dimensions from sixteen patients were anatomically separated into layers (seven hundred and twelve) and an incision made along one-third of their length. They underwent tear testing via uniaxial loading and then unloading before crack propagation had proceeded along their complete length. The average tear tension and tear energy per reference area generated were many-fold greater in outer- (adventitial) compared to inner- (intimal with small medial portion) and middle-layer (medial) strips, explaining why the tear is restricted to the inner wall. They were greater in inner- compared to middle-layer strips of the anterior and left lateral quadrants, suggesting that the tear will propagate to the less-resistant media even if initiated in the intima. In most longitudinally-cut middle- and inner-layer strips, the cracks deviated toward the circumferential direction and tore out through the side, justifying the circumferential course of the tear. Both fracture parameters were significantly higher in the right than the left lateral quadrant in outer-layer strips and the anterior quadrant in middle-layer strips, potentially affecting the circumferential extent of the tear.

Material characterization of ascending thoracic aortic aneurysms is indispensable for the determination of stress distributions across wall thickness and the different aneurysm regions that may be responsible for their catastrophic rupture or dissection, but only few studies have addressed this issue hitherto. In this article, we are presenting our findings of implementing microstructure-based formulations for characterizing layer- and region-specific variations in wall properties, which is a reasonable consensus today. Together, we performed image-based analysis to derive collagen-fiber orientation angles that may serve as validation of the preferred candidate for a fiber-reinforced constitutive descriptor. We considered a four-fiber model with dispersions of fiber angles about the main directions, based on our histological observations, demonstrating a wide distribution of fiber orientations spanning circumferential to longitudinal directions, and its successful implementation to our biomechanical data from tensile testing. However, an in-depth parametric analysis showed that a condensed model without longitudinal-fiber family described the data just as well and did not omit essential histological organization of collagen fibers, while reserving a smaller number of parameters, which makes it advantageous for computational applications. A major aberration from almost all existing models in the literature is the hypothesis made that fibers can support compressive stresses. Such a hypothesis needs further examination but it has the benefits of allowing improved fits to the vanishing transverse stresses under uniaxial test conditions and of properly reflecting the exponential nature of the compressive stress–strain response of aortic tissue, being consistent with observations of collagen being under compression in the unloaded wall.

Multiaxial testing of the small intestinal wall is critical for understanding its biomechanical properties and defining material models, but limited data and material models are available. The aim of the present study was to develop a microstructure-based material model for the small intestine and test whether there was a significant variation in the passive biomechanical properties along the length of the organ. Rat tissue was cut into eight segments that underwent inflation/extension testing, and their nonlinearly hyper-elastic and anisotropic response was characterized by a fiber-reinforced model. Extensive parametric analysis showed a non-significant contribution to the model of the isotropic matrix and circumferential-fiber family, leading also to severe over-parameterization. Such issues were not apparent with the reduced neo-Hookean and (axial and diagonal)-fiber family model, that provided equally accurate fitting results. Absence from the model of either the axial or diagonal-fiber families led to ill representations of the force- and pressure-diameter data, respectively. The primary direction of anisotropy, designated by the estimated orientation angle of diagonal-fiber families, was about 35° to the axial direction, corroborating prior microscopic observations of submucosal collagen-fiber orientation. The estimated model parameters varied across and within the duodenum, jejunum, and ileum, corroborating histologically assessed segmental differences in layer thicknesses.

The human ureters have not been thoroughly explored from the biomechanics perspective, despite the wealth of such data for other soft-tissue types. This study was motivated by the need to use relevant biomechanical data from human ureters and microstructure-based material formulations for simulations of ureteral peristalsis and stenting. Our starting choice was the four-fiber family model that has proven its validity as a descriptor of the multiaxial response of cardiovascular tissues. The degree of model complexity, required for rigorous fits to passive quasi-static pressure-diameter-force data at several axial stretches, was systematically investigated. Ureteral segments from sixteen human autopsy subjects were evaluated. A diagonal and axial family model allowed equally-good fits as the full model for all age groups and ureteral regions; considerably better than those allowed by the phenomenological Fung-type model whose root-mean-square error of fitting was three-fold greater. This reduced model mimicked the structure seen in histologic sections, namely plentiful diagonal collagen fibers in the lamina propria and axial fibers in the muscle and adventitia. The paucity of elastin fibers and mixed muscle orientation justified the use of isotropic muscle-dominated matrix with small neo-Hookean parameter values. The significantly thicker lamina propria in the lower than the upper ureter of young subjects (312 ± 27 vs. 232 ± 26 μm; mean ± standard error) corroborated the significant regional differences in diagonal-fiber family parameter values. The significant muscle thickening with age (upper ureter: 373 ± 48 vs. 527 ± 67 μm; middle: 388 ± 29 vs. 575 ± 69 μm; lower: 440 ± 21 vs. 602 ± 71 μm) corroborated the significant age-related increase in axial-fiber family parameter values.

The esophagus is a multi-layered organ that transports food to the stomach. While extensive biomechanical data exist for animal esophagi, human data remain limited. To address this, we analyzed residual deformations and zero-stress configurations in esophageal tissue from twenty-one cadavers (aged 21-84). Rings were photographed from fifteen equidistant locations before and after radial cutting and dissection into mucosa-submucosa and muscle layers. Image analysis revealed that the opening angles of the intact wall and muscle—slightly greater for the latter—did not vary significantly along the esophagus (p > 0.05 across age groups and genders). Conversely, the mucosa-submucosa had a larger opening angle, increasing along the esophagus (p < 0.05 in young subjects and both genders). Residual strains released by radial cutting and layer separation showed no anatomical position dependence (p > 0.05). The no-load internal circumference remained age-independent (p > 0.05 at all locations), while intact-wall thickness increased from young to middle-aged subjects due to mucosa-submucosa expansion (p < 0.05 in the upper half). No significant muscle growth occurred with age. This correlated with a rise in intact-wall opening angle between those age groups (p < 0.05 at the same sites), driven by more compressive internal residual strain (p < 0.05 near mid-esophagus). Age-related variations in layer-specific opening angles and residual strains were minimal (p > 0.05 in most locations). Males had wider, thicker esophagi (p < 0.05 in the upper half), but gender had no significant effect on opening angles and residual strains. This database provides new insights into the residual strains of the human esophagus and enhances computational simulations of transport and clinical interventions.

Aortic dissection is a life-threatening event, during which a primary tear propagates along the aorta causing catastrophic delamination of the inner (intima with most of the media) from the outer layers (leftover media with adventitia). Our understanding of mode-I fracture resistance at different aortic regions is incomplete, although the anatomical localization of the dissection channel may be assigned to this factor. To determine whether the susceptibility to dissection propagation varied with aortic region, the average and standard deviation of peel tension (indices of adhesive strength between layers when pulled apart and its fluctuation) were measured in 24 cadaveric subjects. Measurements were made in the inner and outer quadrants of 9 consecutive regions. Strong regional heterogeneity was established that was age-related based on the following evidence: (1) the average and standard deviation of peel tension peaked in the ascending aorta, decreasing to almost constant values in the descending thoracic aorta, but increasing across the abdominal aorta; (2) axial differences were more pronounced in the inner quadrant, with differences among quadrants reaching significance proximally; (3) the average peel tension was greatly impaired from <40 to 40–60 but much less to >60-year-old subjects at most regions/quadrants, leading to non-uniform axial variations in all age groups; (4) gender affected little the data. This comprehensive series of delamination tests explains the clinical observation of most dissections initiating in the ascending aorta to extend distally and of few dissections initiating in the descending thoracic aorta to extend proximally, while supporting the increased vulnerability in aged subjects.

The gold standard vascular substitutes, used in cardiovascular surgery, are the Dacron or expanded polytetrafluoroethylene (ePTFE)-derived grafts. However, major adverse reactions accompany their use. For this purpose, decellularized human umbilical arteries (hUAs) may be proven as a significant source for the development of small diameter conduits. The aim of this study was the evaluation of a decellularization protocol in hUAs. To study the effect of the decellularization to the hUAs, histological analysis was performed. Then, native and decellularized hUAs were biochemically and biomechanically evaluated. Finally, broad proteomic analysis was applied. Histological analysis revealed the successful decellularization of the hUAs. Furthermore, a great amount of DNA was removed from the decellularized hUAs. Biomechanical analysis revealed statistically significant differences in longitudinal direction only in maximum stress (p < 0.013) and strain (p < 0.001). On the contrary, all parameters tested for circumferential direction exhibited significant differences (p < 0.05). Proteomic analysis showed the preservation of the extracellular matrix and cytoskeletal proteins in both groups. Proteomic data are available via ProteomeXchange with identifier PXD020187. The above results indicated that hUAs were efficiently decellularized. The tissue function properties of these conduits were well retained, making them ideal candidates for the development of small diameter vascular grafts.

Background: The development of functional bioengineered small-diameter vascular grafts (SDVGs), represents a major challenge of tissue engineering. This study aimed to evaluate the repopulation efficacy of biological vessels, utilizing the cord blood platelet lysate (CBPL). Methods: Human umbilical arteries (hUAs, n = 10) were submitted to decellularization. Then, an evaluation of decellularized hUAs, involving histological, biochemical and biomechanical analysis, was performed. Wharton’s Jelly (WJ) Mesenchymal Stromal Cells (MSCs) were isolated and characterized for their properties. Then, WJ-MSCs (1.5 × 106 cells) were seeded on decellularized hUAs (n = 5) and cultivated with (Group A) or without the presence of the CBPL, (Group B) for 30 days. Histological analysis involving immunohistochemistry (against Ki67, for determination of cell proliferation) and indirect immunofluorescence (against activated MAP kinase, additional marker for cell growth and proliferation) was performed. Results: The decellularized hUAs retained their initial vessel’s properties, in terms of key-specific proteins, the biochemical and biomechanical characteristics were preserved. The evaluation of the repopulation process indicated a more uniform distribution of WJ-MSCs in group A compared to group B. The repopulated vascular grafts of group B were characterized by greater Ki67 and MAP kinase expression compared to group A. Conclusion: The results of this study indicated that the CBPL may improve the repopulation efficacy, thus bringing the biological SDVGs one step closer to clinical application.