Machine intelligence accelerated design of conductive MXene aerogels with programmable properties.

Designing ultralight conductive aerogels with tailored electrical and mechanical properties is critical for various applications. Conventional approaches rely on iterative, time-consuming experiments across a vast parameter space. Herein, an integrated workflow is developed to combine collaborative robotics with machine learning to accelerate the design of conductive aerogels with programmable properties. An automated pipetting robot is operated to prepare 264 mixtures of Ti3C2Tx MXene, cellulose, gelatin, and glutaraldehyde at different ratios/loadings. After freeze-drying, the aerogels' structural integrity is evaluated to train a support vector machine classifier. Through 8 active learning cycles with data augmentation, 162 unique conductive aerogels are fabricated/characterized via robotics-automated platforms, enabling the construction of an artificial neural network prediction model. The prediction model conducts two-way design tasks: (1) predicting the aerogels' physicochemical properties from fabrication parameters and (2) automating the inverse design of aerogels for specific property requirements. The combined use of model interpretation and finite element simulations validates a pronounced correlation between aerogel density and compressive strength. The model-suggested aerogels with high conductivity, customized strength, and pressure insensitivity allow for compression-stable Joule heating for wearable thermal management.

Investigating the Role of Thrombosis, Fenestration, and False Lumen Orbital Orientation in the Hemodynamics of Type B Aortic Dissection.

While much about the fundamental mechanisms behind the initiation and progression of Type B aortic dissection (TBAD) is still unknown, predictive models based on patient-specific computational fluid dynamics (CFD) can help in risk stratification and optimal clinical decision-making. Aiming at the development of personalized treatment, CFD simulations can be leveraged to investigate the interplay between complex aortic flow patterns and anatomical features. In this study, the hemodynamics of false lumen thrombosis, a large fenestration, and the orbital orientation of the false lumen is studied through image-based CFD simulations on three TBAD patient-specific geometries. A new pipeline was developed leveraging the open-source software SimVascular and Paraview to analyze multiple patients simultaneously and to achieve large-scale parallelization in CFD results based on patients' computed tomography (CT) images. The results of this study suggest that the internal orbital orientation of the false lumen contributes to maintaining a positive luminal pressure difference ΔPTL-FL=PTL-PFL between the true lumen (TL) and the false lumen (FL), despite an impingement area in the false lumen near the entry tear. A positive and high luminal pressure difference is thought to promote TL expansion and FL compression. Moreover, it was also found that both FL thrombosis at the entry tear region, and the presence of a large fenestration in the descending thoracic aorta reduce the magnitude of the negative luminal pressure difference, which in turn may reduce FL expansion and the risk of unstable aortic growth.

3D-Printed Microinjection Needle Arrays via a Hybrid DLP-Direct Laser Writing Strategy.

Microinjection protocols are ubiquitous throughout biomedical fields, with hollow microneedle arrays (MNAs) offering distinctive benefits in both research and clinical settings. Unfortunately, manufacturing-associated barriers remain a critical impediment to emerging applications that demand high-density arrays of hollow, high-aspect-ratio microneedles. To address such challenges, here, a hybrid additive manufacturing approach that combines digital light processing (DLP) 3D printing with "ex situ direct laser writing (esDLW)" is presented to enable new classes of MNAs for fluidic microinjections. Experimental results for esDLW-based 3D printing of arrays of high-aspect-ratio microneedles-with 30 µm inner diameters, 50 µm outer diameters, and 550 µm heights, and arrayed with 100 µm needle-to-needle spacing-directly onto DLP-printed capillaries reveal uncompromised fluidic integrity at the MNA-capillary interface during microfluidic cyclic burst-pressure testing for input pressures in excess of 250 kPa (n = 100 cycles). Ex vivo experiments perform using excised mouse brains reveal that the MNAs not only physically withstand penetration into and retraction from brain tissue but also yield effective and distributed microinjection of surrogate fluids and nanoparticle suspensions directly into the brains. In combination, the results suggest that the presented strategy for fabricating high-aspect-ratio, high-density, hollow MNAs could hold unique promise for biomedical microinjection applications.

Functional analysis of arteriovenous fistulae in non-contrast magnetic resonance images.

BACKGROUND AND OBJECTIVE: Arteriovenous fistulae (AVF) are the preferred mode of hemodialysis vascular access and their successful maturation is critical to reduce patient morbidity, mortality, cost, and improve quality of life. Peri-anastomotic venous segment stenosis is the primary cause of AVF maturation failure. The objective is to develop a software protocol for the functional analysis of arteriovenous fistula. METHOD: We have developed a standard protocol for the anatomical analysis of the AVF to better understand the mechanisms involved in AVF stenosis and to identify future imaging biomarkers for AVF success or failure using non-contrast magnetic resonance imaging (MRI). The 3D model of the AVF is created using a polar dynamic programming technique. Analysis has been performed on six Yorkshire cross domestic swine, but techniques can be applied into clinical settings. RESULTS: Differences in AVF angles and vein curvature are associated with significant variability of venous cross-sectional area. This suggests that the pattern of stenosis is likely to be dependent upon hemodynamic profiles which are largely determined by AVF anatomical features and could play an important role in AVF maturation. CONCLUSIONS: This protocol enables us to visualize and study the hemodynamic profiles indirectly allowing early stratification of patients into high and low risk groups for AVF maturation failure. High risk patients could then be targeted with an enhanced process of care or future maturation enhancing therapies resulting in a much-needed precision-medicine approach to dialysis vascular access.

Programming nonreciprocity and reversibility in multistable mechanical metamaterials.

Nonreciprocity can be passively achieved by harnessing material nonlinearities. In particular, networks of nonlinear bistable elements with asymmetric energy landscapes have recently been shown to support unidirectional transition waves. However, in these systems energy can be transferred only when the elements switch from the higher to the lower energy well, allowing for a one-time signal transmission. Here, we show that in a mechanical metamaterial comprising a 1D array of bistable arches nonreciprocity and reversibility can be independently programmed and are not mutually exclusive. By connecting shallow arches with symmetric energy wells and decreasing energy barriers, we design a reversible mechanical diode that can sustain multiple signal transmissions. Further, by alternating arches with symmetric and asymmetric energy landscapes we realize a nonreciprocal chain that enables propagation of different transition waves in opposite directions.

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.

Snapping of hinged arches under displacement control: Strength loss and nonreciprocity.

We investigate experimentally and numerically the response of hinged shallow arches subjected to a transverse midpoint displacement. We find that this simple system supports a rich set of responses, which, to date, have received relatively little attention. We observe not only the snapping of the arches to their inverted equilibrium configuration, but also an earlier dynamic transition from a symmetric to an asymmetric shape that results in a sudden strength loss. Moreover, we find that the response of plastically deformed arches is nonreciprocal with respect to the loading direction. Finally, we discover that, while elastically deformed arches always snap to the inverted stable configuration, for plastically deformed ones there is a critical rise below which the structures are monostable.

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.

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.

Nonlinear Dynamics of Dacron Aortic Prostheses Conveying Pulsatile Flow.

This study addresses the dynamic response to pulsatile physiological blood flow and pressure of a woven Dacron graft currently used in thoracic aortic surgery. The model of the prosthesis assumes a cylindrical orthotropic shell described by means of nonlinear Novozhilov shell theory. The blood flow is modeled as Newtonian pulsatile flow, and unsteady viscous effects are included. Coupled fluid-structure Lagrange equations for open systems with wave propagation subject to pulsatile flow are applied. Physiological waveforms of blood pressure and velocity are approximated with the first eight harmonics of the corresponding Fourier series. Time responses of the prosthetic wall radial displacement are considered for two physiological conditions: at rest (60 bpm) and at high heart rate (180 bpm). While the response at 60 bpm reproduces the behavior of the pulsatile pressure, higher harmonics frequency contributions are observed at 180 bpm altering the shape of the time response. Frequency-responses show resonance peaks for heart rates between 130 bpm and 200 bpm due to higher harmonics of the pulsatile flow excitation. These resonant peaks correspond to unwanted high-frequency radial oscillations of the vessel wall that can compromise the long-term functioning of the prosthesis in case of significant physical activity. Thanks to this study, the dynamic response of Dacron prostheses to pulsatile flow can be understood as well as some possible complications in case of significant physical activity.