Single Hydrogel Particle Mechanics and Dynamics Studied by Combining Capillary Micromechanics with Osmotic Compression.

Hydrogels can exhibit a remarkably complex response to external stimuli and show rich mechanical behavior. Previous studies of the mechanics of hydrogel particles have generally focused on their static, rather than dynamic, response, as traditional methods for measuring single particle response at the microscopic scale cannot readily measure time-dependent mechanics. Here, we study both the static and the time-dependent response of a single batch of polyacrylamide (PAAm) particles by combining direct contact forces, applied by using Capillary Micromechanics, a method where particles are deformed in a tapered capillary, and osmotic forces are applied by a high molecular weight dextran solution. We found higher values of the static compressive and shear elastic moduli for particles exposed to dextran, as compared to water (KDex≈63 kPa vs. Kwater≈36 kPa, and GDex≈16 kPa vs. Gwater≈7 kPa), which we accounted for, theoretically, as being the result of the increased internal polymer concentration. For the dynamic response, we observed surprising behavior, not readily explained by poroelastic theories. The particles exposed to dextran solutions deformed more slowly under applied external forces than did those suspended in water (τDex≈90 s vs. τwater≈15 s). The theoretical expectation was the opposite. However, we could account for this behaviour by considering the diffusion of dextran molecules in the surrounding solution, which we found to dominate the compression dynamics of our hydrogel particles suspended in dextran solutions.

A Prototype System With Custom-Designed RX ICs for Contrast-Enhanced Ultrasound Imaging.

This work presents a prototype system based on a multichannel receiving (RX) integrated circuit (IC) for contrast-enhanced ultrasound (CEUS) imaging. The RX IC is implemented in a 40-nm low-voltage CMOS technology and is designed to interface to a capacitive micromachined ultrasonic transducer array. To enable a direct connection of the RX electronics to the transducer, an analog multiplexer with on-chip protection circuitry is developed. Stress tests confirm the reliability of this arrangement when combined with a high-voltage pulser. The RX IC is equipped with a highly programmable bandpass filter to capture harmonic signals from ultrasound contrast agents (UCAs) while suppressing fundamental components. In order to examine the impact of analog front-end (AFE) bandpass filtering, in vitro acoustic experiments are performed with UCAs. A spatial resolution analysis suggests that the AFE bandpass filtering combined with a pulse inversion (PI) technique can improve the lateral resolution by 38% or 9% compared to the original full-bandwidth approach or a stand-alone PI approach, respectively, while the impact on axial resolution is negligible. A phantom study shows that compared to digital bandpass filtering, the AFE bandpass filtering enables better use of the dynamic range of the RX electronics, resulting in better generalized contrast-to-noise ratio from 0.44/0.53 to 0.57/0.68 without or with PI.

Acoustic characterization of tissue-mimicking materials for ultrasound perfusion imaging research.

Materials with well-characterized acoustic properties are of great interest for the development of tissue-mimicking phantoms with designed (micro)vasculature networks. These represent a useful means for controlled in-vitro experiments to validate perfusion imaging methods such as Doppler and contrast-enhanced ultrasound (CEUS) imaging. In this work, acoustic properties of seven tissue-mimicking phantom materials at different concentrations of their compounds and five phantom case materials are characterized and compared at room temperature. The goal of this research is to determine the most suitable phantom and case material for ultrasound perfusion imaging experiments. The measurements show a wide range in speed of sound varying from 1057 to 1616 m/s, acoustic impedance varying from 1.09 to 1.71 × 106 kg/m2s, and attenuation coefficients varying from 0.1 to 22.18 dB/cm at frequencies varying from 1 MHz to 6 MHz for different phantom materials. The nonlinearity parameter B/A varies from 6.1 to 12.3 for most phantom materials. This work also reports the speed of sound, acoustic impedance and attenuation coefficient for case materials. According to our results, polyacrylamide (PAA) and polymethylpentene (TPX) are the optimal materials for phantoms and their cases, respectively. To demonstrate the performance of the optimal materials, we performed power Doppler ultrasound imaging of a perfusable phantom, and CEUS imaging of that phantom and a perfusion system. The obtained results can assist researchers in the selection of the most suited materials for in-vitro studies with ultrasound imaging.

Recapitulating the Vasculature Using Organ-On-Chip Technology.

The development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.

3D Sugar Printing of Networks Mimicking the Vasculature.

The vasculature plays a central role as the highway of the body, through which nutrients and oxygen as well as biochemical factors and signals are distributed by blood flow. Therefore, understanding the flow and distribution of particles inside the vasculature is valuable both in healthy and disease-associated networks. By creating models that mimic the microvasculature fundamental knowledge can be obtained about these parameters. However, microfabrication of such models remains a challenging goal. In this paper we demonstrate a promising 3D sugar printing method that is capable of recapitulating the vascular network geometry with a vessel diameter range of 1 mm down to 150 µm. For this work a dedicated 3D printing setup was built that is capable of accurately printing the sugar glass material with control over fibre diameter and shape. By casting of printed sugar glass networks in PDMS and dissolving the sugar glass, perfusable networks with circular cross-sectional channels are obtained. Using particle image velocimetry, analysis of the flow behaviour was conducted showing a Poisseuille flow profile inside the network and validating the quality of the printing process.

A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions.

Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of the native tissue nor do they allow examination of cell-cell interactions under relevant hemodynamic conditions. Here, we describe a 3D microfluidic chip model of arterial endothelial and smooth muscle cells where cellular organization, composition and interactions, as well as the mechanical environment of the arterial wall are mimicked. The hemodynamic EC-VSMC-signalling-on-a-chip consists of two parallel polydimethylsiloxane (PDMS) cell culture channels, separated by a flexible, porous PDMS membrane, mimicking the porosity of the internal elastic lamina. The hemodynamic EC-VSMC-signalling-on-a-chip allows co-culturing of human aortic endothelial cells (ECs) and human aortic vascular smooth muscle cells (VSMCs), separated by a porous membrane, which enables EC-VSMC interaction and signalling, crucial for the development and homeostasis of the vessel wall. The device allows real time cell imaging and control of hemodynamic conditions. The culture channels are surrounded on either side by vacuum channels to induce cyclic strain by applying cyclic suction, resulting in mechanical stretching and relaxation of the membrane in the cell culture channels. The blood flow is mimicked by creating a flow of medium at the EC side. Vascular cells remain viable during prolonged culturing, exhibit physiological morphology and organization and make cell-cell contact. During dynamic culturing of the device with a shear stress of 1-1.5 Pa and strain of 5-8%, VSMCs align perpendicular to the given strain in the direction of the flow and EC adopt a cobblestone morphology. To our knowledge, this is the first report on the development of a microfluidic device, which enables a co-culture of interacting ECs and VSMCs under hemodynamic conditions and presents a novel approach to systematically study the biological and mechanical components of the intimal-medial vascular unit.