Experimental characterization of residual deformations in human descending thoracic aortas.

The effect of residual stresses on the deformation of human aortas under pulsatile pressure is relevant. Experimental measurements of residual deformations are necessary to characterize residual stresses in human aortas. For this reason, an experimental study is carried out. In the present study, longitudinal and circumferential strips from descending thoracic aortas obtained from 21 donors, harvested during organ donation explant, underwent residual deformation measurements. The intact wall and the three separated layers were tested in both directions, resulting in 8 tests per donor, which gives a relevant set of experimental data for further studies. Results show significant residual deformations both in circumferential and longitudinal directions, which are compatible with a significantly compressed intima in the unloaded aorta. In particular, the measured mean effective curvature was -0.193 ± 0.064 (1/mm) for the circumferential strips and -0.076 ± 0.030 (1/mm) for longitudinal strips of the full wall. The effects of age and gender were also investigated.

Active and passive mechanical characterization of a human descending thoracic aorta with Klippel-Trenaunay syndrome.

A human aorta from a female donor affected by Klippel-Trenaunay syndrome was retrieved during a surgery for organ donation for transplant. The aorta was preserved in refrigerated Belzer UW organ preservation solution and tested within a few hours for mechanical characterization with and without vascular smooth muscle activation. KCl and Noradrenaline were used as vasoactive agents in bubbled Krebs-Henseleit buffer solution at 37 °C. A quasi-static and a dynamic mechanical characterization of the full wall and the three individual layers were carried out for strips taken in longitudinal and circumferential directions. The full wall in the descending portion of the aorta underwent mechanical tests with and without smooth muscle activation. Results were compared to data obtained from healthy aortas and show a reduced stiffness of the full wall in circumferential direction. Also, a significant reduction of the response to vasoactive agents in circumferential direction was observed, while the longitudinal response was similar to healthy cases.

Jacketed elastomeric tubes for passive self-regulation of pulsatile flow.

Regulating pulsatile flow is important to achieve optimal separation and mixing and enhanced heat transfer in microfluidic devices, as well as maintaining homeostasis in biological systems. The human aorta, a composite and layered tube made (among others) of elastin and collagen, is an inspiration for researchers who seek an engineering solution for a self-regulation of pulsatile flow. Here, we present a bio-inspired approach showing that fabric-jacketed elastomeric tubes, manufactured using commercially available silicone rubber and knitted textiles, can be used to regulate pulsatile flow. Our tubes are evaluated via incorporation into a mock-circulatory 'flow loop' that replicates the pulsatile fluid flow conditions of an ex-vivo heart perfusion (EVHP) device, a machine used in heart transplants. Pressure waveforms measured near the elastomeric tubing clearly indicated an effective flow regulation. The 'dynamic stiffening' behavior of the tubes during deformation is analyzed quantitatively. Broadly, the fabric jackets allow for the tubes to experience greater magnitudes of pressure and distension without risk of asymmetric aneurysm within the expected operating time of an EVHP. Owing to its highly tunable nature, our design may serve as a basis for tubing systems that require passive self-regulation of pulsatile flow.

A review on the biomechanical behaviour of the aorta.

Large aortic aneurysm and acute and chronic aortic dissection are pathologies of the aorta requiring surgery. Recent advances in medical intervention have improved patient outcomes; however, a clear understanding of the mechanisms leading to aortic failure and, hence, a better understanding of failure risk, is still missing. Biomechanical analysis of the aorta could provide insights into the development and progression of aortic abnormalities, giving clinicians a powerful tool in risk stratification. The complexity of the aortic system presents significant challenges for a biomechanical study and requires various approaches to analyse the aorta. To address this, here we present a holistic review of the biomechanical studies of the aorta by categorising articles into four broad approaches, namely theoretical, in vivo, experimental and combined investigations. Experimental studies that focus on identifying mechanical properties of the aortic tissue are also included. By reviewing the literature and discussing drawbacks, limitations and future challenges in each area, we hope to present a more complete picture of the state-of-the-art of aortic biomechanics to stimulate research on critical topics. Combining experimental modalities and computational approaches could lead to more comprehensive results in risk prediction for the aortic system.

Development and mechanical characterization of decellularized scaffolds for an active aortic graft.

Decellularized porcine aortas are proposed as scaffolds for revolutionary active aortic grafts. A change in the static and dynamic mechanical properties, associated with the microstructure of elastin and collagen fibers, corresponds to alteration in the cyclic expansion and perfusion, in addition to possible graft damage. Therefore, the present study thoroughly investigates the mechanical response of the decellularized scaffolds of human and porcine origin to static and dynamic mechanical loads. The responses of the native human and porcine aortas are also compared; this is unavailable in the literature. Because the aorta is subjected to pulsatile blood pressure, dynamical responses to cyclic loads and their associated viscoelastic properties are particularly relevant for advanced graft design. In parallel, this study examines the microstructure of the decellularized aorta. The resulting data are compared to the analogous data obtained for the native human and porcine tissues. The results indicate that by using an optimized decellularization protocol - based on sodium dodecyl sulfate (SDS) and DNase - that minimizes mechanical and structural changes of the tissue, layered scaffolds with static and dynamic properties very similar to natural human aortas are obtained. In particular, a decellularized porcine aorta is non-inferior to a decellularized human aorta. STATEMENT OF SIGNIFICANCE: About 55,000 patients undergo abdominal aortic aneurysm repair annually in the USA. The currently implanted grafts present a large mechanical mismatch with the native tissue. This increases the pulsatile nature of the blood flow with negative consequences to the organ perfusion. For this reason, biomimetic and mechanically compatible grafts for aortic repair are urgently needed and they can be obtained through tissue engineering. In this study, scaffolds from porcine and human aortas are obtained from an optimized decellularization protocol. They are accurately compared to the native tissue and present the ideal static and dynamic mechanical properties for developing innovative aortic grafts.

Fitting mechanical properties of the aortic wall and individual layers to experimental tensile tests including residual stresses.

The authors have observed that a stress-strain curve for uniaxial tension of an aortic intact wall cannot be simply obtained by combining the strain energy functions of the three individual aortic layers - intima, media and adventitia - even taking into account the interaction among the three layers; the strain energy functions of the three layers are obtained fitting tensile tests on strips from the individual layers. Due to the layer separation, the residual stresses are released and thus they do not affect the stress-strain curves of the individual layers. The present study shows that it is instead possible to fit the intact wall experimental curves with the combination of the strain energy functions of the three individual layers if residual strains are added. The residual strains are used as optimization parameters with specific constraints and allowing for the buckling (wrinkling) of the intima under unpressurized condition of the aortic wall, as experimentally observed. By varying these parameters in the experimentally observed range of values, it is possible to find a solution with the combined responses of the individual layers matching the experimental stress-strain curves of the intact wall.

Liquid-infused microstructured bioadhesives halt non-compressible hemorrhage.

Non-compressible hemorrhage is an unmet clinical challenge that accounts for high mortality in trauma. Rapid pressurized blood flows under hemorrhage impair the function and integrity of hemostatic agents and the adhesion of bioadhesive sealants. Here, we report the design and performance of bioinspired microstructured bioadhesives, formed with a macroporous tough xerogel infused with functional liquids. The xerogel can rapidly absorb interfacial fluids such as whole blood and promote blood clotting, while the infused liquids facilitate interfacial bonding, sealing, and antibacterial function. Their synergy enables the bioadhesives to form tough adhesion on ex vivo human and porcine tissues and diverse engineered surfaces without the need for compression, as well as on-demand instant removal and storage stability. We demonstrate a significantly improved hemostatic efficacy and biocompatibility in rats and pigs compared to non-structured counterparts and commercial products. This work opens new avenues for the development of bioadhesives and hemostatic sealants.

Viscoelasticity of human descending thoracic aorta in a mock circulatory loop.

Healthy human descending thoracic aortas, obtained during organ donation for transplant and research, were tested in a mock circulatory loop to measure the mechanical response to physiological pulsatile pressure and flow. The viscoelastic properties of the aortic segments were investigated at three different pulse rates. The same aortic segments were also subjected to quasi-static pressure tests in order to identify the aortic dynamic stiffness ratio, which is defined as the ratio between the stiffness in case of pulsatile pressure and the stiffness measured for static pressurization, both at the same value of pressure. The loss factor was also identified. The shape of the deformed aorta under static and dynamic pressure was measured by image processing to verify the compatibility of the end supports with the natural deformation of the aorta in the human body. In addition, layer-specific experiments on 10 human descending thoracic aortas allowed to precisely identify the mass density of the aortic tissue, which is an important parameter in cardiovascular dynamic models.

Role of smooth muscle activation in the static and dynamic mechanical characterization of human aortas.

Experimental data and a suitable material model for human aortas with smooth muscle activation are not available in the literature despite the need for developing advanced grafts; the present study closes this gap. Mechanical characterization of human descending thoracic aortas was performed with and without vascular smooth muscle (VSM) activation. Specimens were taken from 13 heart-beating donors. The aortic segments were cooled in Belzer UW solution during transport and tested within a few hours after explantation. VSM activation was achieved through the use of potassium depolarization and noradrenaline as vasoactive agents. In addition to isometric activation experiments, the quasistatic passive and active stress-strain curves were obtained for circumferential and longitudinal strips of the aortic material. This characterization made it possible to create an original mechanical model of the active aortic material that accurately fits the experimental data. The dynamic mechanical characterization was executed using cyclic strain at different frequencies of physiological interest. An initial prestretch, which corresponded to the physiological conditions, was applied before cyclic loading. Dynamic tests made it possible to identify the differences in the viscoelastic behavior of the passive and active tissue. This work illustrates the importance of VSM activation for the static and dynamic mechanical response of human aortas. Most importantly, this study provides material data and a material model for the development of a future generation of active aortic grafts that mimic natural behavior and help regulate blood pressure.

Microstructural and mechanical characterization of the layers of human descending thoracic aortas.

The mechanical properties of human aortas are linked to the layered tissue and its microstructure at different length scales. Each layer has specific mechanical and structural properties. While the ground substance and the elastin play an important role in tissue stiffness at small strain, collagen fibers carry most of the load at larger strains, which corresponds to the physiological conditions of the aorta at maximum pulsatile blood pressure. In fact, collagen fibers are crimped in the unloaded state. Collagen fibers show different orientation distributions when they are observed in a plane that is tangent to the aortic wall (in-plane section) or along a direction orthogonal to it (out-of-plane section). This was systematically investigated using large images (2500 × 2500 µm) with high resolution obtained by second harmonic generation (SHG) in order to homogenize tissue heterogeneity after a convergence analysis, which is a main goal of the study. In addition, collagen fibers show lateral interactions due to entanglements and the presence of transverse elastin fibers, observed on varying length scales using atomic force microscopy and a three-dimensional rendering obtained by stacking a sequence of SHG and two-photon fluorescence images; this is another important contribution. Human descending thoracic aortas from 13 heartbeat donors aged 28 to 66 years were examined. Uniaxial tensile tests were carried out on the longitudinal and circumferential strips of the aortic wall and the three separated layers (intima, media and adventitia). A structurally-motivated material model with (i) a term to describe the combined response of ground substance and elastin and (ii) terms to consider four families of collagen fibers with different directions was applied. The exclusion of compressed fibers was implemented in the fitting process of the experimental data, which was optimized by a genetic algorithm. The results show that a single fiber family with directional and dispersion parameters measured from SHG images can describe the mechanical response of all 39 layers (3 layers for each of the 13 aortas) with very good accuracy when a second (auxiliary) family of aligned fibers is introduced in the orthogonal direction to account for lateral fiber interaction. Indeed, all observed distributions of collagen directions can be accurately fitted by a single bivariate von Mises distribution. Statistical analysis of in-plane and out-of-plane dispersion of fiber orientations reveals structural differences between the three layers and a change of collagen dispersion parameters with age. STATEMENT OF SIGNIFICANCE: The stiffness of healthy young aortas is adjusted so that a diameter expansion of about 10 % is possible during the heartbeat. This creates the Windkessel effect, which smooths out the pulsating nature of blood flow and benefits organ perfusion. The specific elastic properties of the aorta that are required to achieve this effect are related to the microstructure of the aortic tissue at different length scales. An increase in the aortic stiffness, in addition to reducing cyclic expansion and worsening perfusion, is a risk factor for clinical hypertension. The present study relates the microstructure of healthy human aortas to the mechanical response and examines the changes in microstructural parameters with age, which is a key factor in increasing stiffness.

Viscoelastic characterization of human descending thoracic aortas under cyclic load.

Experiments were carried out on 15 human descending thoracic aortas from heart-beating healthy donors who donated organs for transplant. The aortas were kept refrigerated in organ preservation solution and tested were completed within 48 hours from explant. Donors' age was comprised between 25 and 70 years, with an average of 51.7 ± 12.8 years. Quasi-static and dynamic uniaxial tensile test were carried out in thermally controlled physiological saline solution in order to characterize the viscoelastic behavior. Strips were tested under harmonic deformation of different frequency, between 1 and 11 Hz, at three initial pre-stretches. Cyclic deformations of two different amplitudes were used: a physiological one and a small one, the latter one for comparison purposes to understand the accuracy limits of viscoelastic models. Aortic strips in circumferential and longitudinal directions were cut from each aorta. Some strips were dissected to separate the three layers: intima, media and adventitia. They were tested individually in order to obtain layer-specific data. However, strips of the intact wall were also tested. Therefore, 8 strips per donors were tested. Viscoelastic parameters are accurately evaluated from the hysteresis loops. Results show that small-amplitude cyclic strain over-estimate the storage modulus and under-estimate the loss-factor. Therefore, cyclic deformation of physiological amplitude is necessary to obtain correct viscoelastic data of aortic tissue. The value of the applied pre-stretch is significant on the dynamic stiffness ratio (storage modulus divided by the corresponding quasi-static stiffness), while it is less significant for the loss factor. The median of the dynamic stiffness ratios, in physiological conditions, varies between 1.14 and 1.33 for the different layers and the intact wall; the corresponding median of the loss factors varies between 0.050 and 0.066. The lowest dynamic stiffness ratios and loss factors were obtained from donors of the youngest age group. STATEMENT OF SIGNIFICANCE: There is an increasing interest in replacing traditional Dacron grafts used to repair thoracic aortas after acute dissection and aneurysm, with grafts in innovative biomaterials that mimic the mechanical properties and the dynamic behavior of the aorta. The human aorta is a complex laminated structure with hyperelastic and viscoelastic material properties and residual stresses. This study aims to characterize the nonlinear viscoelastic properties of ex-vivo human descending thoracic aortas by measuring hysteresis loops of physiological amplitude under harmonic strain. Results show the necessity to characterize the viscoelastic material properties of the aorta under physiological conditions, as well as the necessity to introduce improved models that take better into account the influence of the initial pre-stretch and amplitude of the cyclic load.

Effect of fiber exclusion in uniaxial tensile tests of soft biological tissues.

The effect of the exclusion of the compressed fibers in the identification of material parameters from uniaxial tensile tests on two orthogonal strips is investigated. The micro-structurally based constitutive model with two dispersion parameters developed by Holzapfel and his colleagues is utilized in the study. A new exclusion method, based on the coefficient reflecting the percentage of stretched fibers, is proposed. The material parameters are identified by using experimental data from 30 uniaxial tensile tests (5 donors, 6 strips per donor) and a genetic algorithm code that is capable to find the optimal set of parameters. The contraction of the strip width computed by using the hyperelastic model with the identified material parameters is compared to the experimental data for two human aortas (one from literature and one experiment, specific for this study), in order to show the accuracy of the identified model. The complex behavior of the thickness deformation of the strip is also obtained and compared to the experimental data derived from in-plane measurements and the incompressibility condition. Results show that the in-plane fiber exclusion is appropriate for aortic material characterization with uniaxial tensile tests, reducing very significantly the computational cost. At the same time, thickness growth of strips during uniaxial tests is possible, depending on fiber dispersion and orientation.

Identification of viscoelastic properties of Dacron aortic grafts subjected to physiological pulsatile flow.

In vascular surgery, most synthetic vascular grafts currently used for large vessels replacements are made of Dacron (polyethylene terephthalate; PET). In this study, the dynamic response of these synthetic arterial substitutes to physiological pulsatile conditions is investigated in depth. Experiments were performed on a mock circulatory loop developed to replicate physiological pulsatile pressure and flow. Two different models of Dacron grafts (branched and straight) were tested at various heart rate conditions. Results are presented in terms of cyclic axisymmetric diameter changes, hysteretic loops of the pressure-diameter change, and viscoelastic parameters, such as loss factor and storage modulus that are identified from the hysteresis loop. The amplitude of cyclic diameter change of the Dacron graft was found to be always below 0.2% for all the heart rates considered (from 57 to 187 bpm). The loss factor of the Dacron graft slightly increased with the heart rate; almost no effect of the pulse rate was observed on the storage modulus, which was identified to be around 100 MPa. Both glycerol-water mixture (i.e. the blood analogue fluid) and saline solution were used in the circulatory loop and results did not present significant differences between the two cases. This shows that the effect of the shear load on the dynamic response of Dacron grafts is negligible. A comparison between Dacron vascular implants and human thoracic aortas shows a large mismatch in their viscoelastic mechanical properties.

Biomechanical characterization of a chronic type a dissected human aorta.

Aortic dissection is one of the most lethal cardiovascular diseases. A chronic Type A (Stanford) dissected aorta was retrieved for research from a 73-year-old male donor without diagnosed genetic disease. The aorta presented a dissection over the full length, and it reached a diameter of 7.7 cm in its ascending portion. The descending thoracic aorta underwent layer-specific quasi-static and dynamic mechanical characterizations after layer separation. Mechanical tests showed a physiological (healthy) behavior of the intima and some mechanical anomalies of the media and the adventitia. In particular, the static stiffness of both these layers at smaller strains was three times smaller than any one measured for twelve healthy aortas. When the viscoelastic properties were tested, adventitia presented a larger relative increase of the dynamic stiffness at 3 Hz with respect to most of the healthy aortas. The loss factor of the adventitia, which is associated with dissipation, was at the lower limit of those measured for healthy aortas. It seems reasonable to attribute these anomalies of the mechanical properties exhibited by the media and the adventitia to the severe remodeling secondary to the chronic nature of the dissection. However, it cannot be excluded that some of the mechanical anomalies were present before remodeling.

Anisotropic fractional viscoelastic constitutive models for human descending thoracic aortas.

The generalized fractional Maxwell model, formulated for hyperelastic material within the framework of the nonlinear viscoelasticity with internal variables, is applied to identify viscoelastic constitutive equations from layer-specific experimental data obtained by uniaxial harmonic loading of ex-vivo human descending thoracic aortas. The constitutive parameters are identified by using a genetic algorithm for the optimal fitting of the experimental data. The accuracy of the fitted fractional model is compared to the fitted integer order model with the same number of Maxwell elements. The formulation of an original strain energy density function for anisotropic nonlinear viscoelasticity is introduced and constitutive parameters are obtained from the experiments.

Layer-specific hyperelastic and viscoelastic characterization of human descending thoracic aortas.

A layer-specific hyperelastic and viscoelastic characterization of human descending thoracic aortas was experimentally performed. Healthy aortas from twelve beating heart donors with an average age of 49.4 years, were received from Transplant Québec. Axial and circumferential strips were prepared from the specimens. They were dissected into intima, media and adventitia layers. Measurements of the opening angles were used to identify the circumferential residual stresses. Uniaxial tensile tests on axial and circumferential strips, together with the Gasser-Ogden-Holzapfel material model, were used to characterize the hyperelastic behaviour of the three aortic layers for each donor. Uniaxial harmonic excitations at different frequency, superimposed to initial stretch values, were used to characterize the viscoelastic behaviour. The storage modulus and the loss tangent were obtained for each layer in both directions; comparison to intact aortic wall was also performed. The generalized Maxwell model, within the framework of nonlinear viscoelasticity with internal variables, was used to obtain the constitutive material parameters. Results showed a positive correlation (p < 0.05 for circumferential media and adventitia) between stiffness and donor age for the three layers of the aorta in both axial and circumferential directions. A significant increase (around 50%) of the storage modulus (i.e. dynamic stiffness) was observed between the quasi-static value and loading at 1 Hz frequency, while further increase in frequency marginally affected its value. The loss tangent was only slightly influenced by the stretch value, which justified the use of the viscoelastic model adopted. Finally, similar loss tangent values were found for the three aortic layers.

Experiments on dynamic behaviour of a Dacron aortic graft in a mock circulatory loop.

Woven Dacron grafts are currently used for the surgical treatment of aortic aneurysm and acute dissection, two otherwise fatal pathologies when aortic wall rupture occurs. While Dacron is chosen for aortic grafts because of characteristics such as biocompatibility and durability, few data are available about the dynamic response of Dacron prosthetic devices and about their side effects on the cardiovascular system. In this study, a Dacron graft was subjected to physiological flow conditions in a specifically-developed mock circulatory loop. Experiments were conducted at different physiological pulsation-per-minute rates. Results show that, in comparison to an aortic segment of the same length, the prosthesis is extremely stiffer circumferentially, thus limiting the dynamical radial expansion responsible for the Windkessel effect in human arteries. The prosthesis is instead excessively compliant in the axial direction and develops preferentially bending oscillations. This very different dynamic behaviour with respect to the human aorta can alter cardiovascular pressure and flow dynamics resulting in long-term implant complications.

A Paper-Based Piezoelectric Accelerometer.

This paper presents the design and testing of a one-axis piezoelectric accelerometer made from cellulose paper and piezoelectric zinc oxide nanowires (ZnO NWs) hydrothermally grown on paper. The accelerometer adopts a cantilever-based configuration with two parallel cantilever beams attached with a paper proof mass. A piece of U-shaped, ZnO-NW-coated paper is attached on top of the parallel beams, serving as the strain sensing element for acceleration measurement. The electric charges produced from the ZnO-NW-coated paper are converted into a voltage output using a custom-made charge amplifier circuit. The device fabrication only involves cutting of paper and hydrothermal growth of ZnO NWs, and does not require the access to expensive and sophisticated equipment. The performance of the devices with different weight growth percentages of the ZnO NWs was characterized.

Nonlinear model of human descending thoracic aortic segments with residual stresses.

The nonlinear static deformation of human descending thoracic aortic segments is investigated. The aorta segments are modeled as straight axisymmetric circular cylindrical shells with three hyperelastic anisotropic layers and residual stresses by using an advanced nonlinear shell theory with higher-order thickness deformation not available in commercial finite element codes. The residual stresses are evaluated in the closed configuration in an original way making use of the multiplicative decomposition. The model was initially validated through comparison with published numerical and experimental data for artery and aorta segments. Then, two different cases of healthy thoracic descending aorta segments were numerically simulated. Material data and residual stresses used in the models came from published layer-specific experiments for human aortas. The material model adopted in the study is the mechanically based Gasser-Ogden-Holzapfel, which takes into account collagen fiber dispersion. Numerical results present a difference between systolic and diastolic inner radii close to the data available in literature from in vivo measurements for the corresponding age groups. Constant length of the aortic segment between systolic and diastolic pressures was obtained for the material model that takes the dispersion of the fiber orientations into account.

Viscoelastic characterization of woven Dacron for aortic grafts by using direction-dependent quasi-linear viscoelasticity.

In case of direction-dependent viscoelasticity, a simplified formulation of the three-dimensional quasi-linear viscoelasticity has been obtained manipulating the original Fung equation. The experimental characterization of the static hyperelastic behaviour, the relaxation, the dynamic modulus and the loss factor of woven Dacron from a commercial aortic prosthesis has been performed. An 11% difference of the reduced relaxation (after infinite time) between axial and circumferential directions has been observed for the woven Dacron. A very large increase in stiffness is obtained in case of harmonic loading with respect to the static loading. These findings are particularly relevant for dynamic modelling of currently used aortic grafts.