Coaxial bioprinting of a stentable and endothelialized human coronary artery-sized in vitro model.

Atherosclerosis accounts for two-thirds of deaths attributed to cardiovascular diseases, which continue to be the leading cause of mortality. Current clinical management strategies for atherosclerosis, such as angioplasty with stenting, face numerous challenges, including restenosis and late thrombosis. Smart stents, integrated with sensors that can monitor cardiovascular health in real-time, are being developed to overcome these limitations. This development necessitates rigorous preclinical trials on either animal models or in vitro models. Despite efforts being made, a suitable human-scale in vitro model compatible with a cardiovascular stent has remained elusive. To address this need, this study utilizes an in-bath bioprinting method to create a human-scale, freestanding in vitro model compatible with cardiovascular stents. Using a coaxial nozzle, a tubular structure of human coronary artery (HCA) size is bioprinted with a collagen-based bioink, ensuring good biocompatibility and suitable rheological properties for printing. We precisely replicated the dimensions of the HCA, including its internal diameter and wall thickness, and simulated the vascular barrier functionality. To simplify post-processing, a pumpless perfusion bioreactor is fabricated to culture a HCA-sized model, eliminating the need for a peristaltic pump and enabling scalability for high-throughput production. This model is expected to accelerate stent development in the future.

Acoustofluidic separation of prolate and spherical micro-objects.

Most microfluidic separation techniques rely largely on object size as a separation marker. The ability to separate micro-objects based on their shape is crucial in various biomedical and chemical assays. Here, we develop an on-demand, label-free acoustofluidic method to separate prolate ellipsoids from spherical microparticles based on traveling surface acoustic wave-induced acoustic radiation force and torque. The freely rotating non-spherical micro-objects were aligned under the progressive acoustic field by the counterrotating radiation torque, and the major axis of the prolate ellipsoids was parallel to the progressive wave propagation. The specific alignment of the ellipsoidal particles resulted in a reduction in the cross-sectional area perpendicular to the wave propagation. As a consequence, the acoustic backscattering decreased, resulting in a decreased magnitude of the radiation force. Through the variation in radiation force, which depended on the micro-object morphology enabled the acoustofluidic shape-based separation. We conducted numerical simulations for the wave scattering of spherical and prolate objects to elucidate the working mechanism underlying the proposed method. A series of experiments with polystyrene microspheres, prolate ellipsoids, and peanut-shaped microparticles were performed for validation. Through quantitative analysis of the separation efficiency, we confirmed the high purity and high recovery rate of the proposed acoustofluidic shape-based separation of micro-objects. As a bioparticle, we utilize Thalassiosira eccentrica to perform shape-based separation, as the species has a variety of potential applications in drug delivery, biosensing, nanofabrication, bioencapsulation and immunoisolation.

Residue-free acoustofluidic manipulation of microparticles via removal of microchannel anechoic corner.

Surface acoustic wave (SAW)-based acoustofluidics has shown significant promise to manipulate micro/nanoscale objects for biomedical applications, e.g. cell separation, enrichment, and sorting. A majority of the acoustofluidic devices utilize microchannels with rectangular cross-section where the acoustic waves propagate in the direction perpendicular to the sample flow. A region with weak acoustic wave intensity, termed microchannel anechoic corner (MAC), is formed inside a rectangular microchannel of the acoustofluidic devices where the ultrasonic waves refract into the fluid at the Rayleigh angle with respect to the normal to the substrate. Due to the absence of a strong acoustic field within the MAC, the microparticles flowing adjacent to the microchannel wall remain unaffected by a direct SAW-induced acoustic radiation force (ARF). Moreover, an acoustic streaming flow (ASF) vortex produced within the MAC pulls the particles further into the corner and away from the direct ARF influence. Therefore, a residue of particles continues to flow past the SAWs without intended deflection, causing a decrease in microparticle manipulation efficiency. In this work, we introduce a cross-type acoustofluidic device composed of a half-circular microchannel, fabricated through a thermal reflow of a positive photoresist mold, to overcome the limitations associated with rectangular microchannels, prone to the MAC formation. We investigated the effects of different microchannel cross-sectional shapes with varying contact angles on the microparticle deflection in a continuous flow and found three distinct regimes of particle deflection. By systematically removing the MAC out of the microchannel cross-section, we achieved residue-free acoustofluidic microparticle manipulation via SAW-induced ARF inside a half-circular microchannel. The proposed method was applied to efficient fluorescent coating of the microparticles in a size-selective manner without any residue particles left undeflected in the MAC.