RESUMO
Drug-induced cardiotoxicity is a significant contributor to drug recalls, primarily attributed to limitations in existing drug screening platforms. Traditional heart-on-a-chip platforms often employ metallic electrodes to record cardiomyocyte electrical signals. However, this approach hinders direct cardiomyocyte morphology observation and typically yields limited functionality. Consequently, this limitation may lead to an incomplete understanding of cardiomyocyte characteristics. To address these challenges, we introduce a multifunctional cardiac microphysiological system featuring transparent indium tin oxide electrodes. This innovative design aims to overcome the limitations of conventional heart-on-a-chip systems where metal electrodes interfere with the observation of cells and increase the difficulty of subsequent image processing of cell images. In addition to facilitating optical measurement combined with image processing capabilities, this system integrates a range of electrodes with diverse functionalities. These electrodes can realize cellular electrical stimulation, field potential monitoring, and impedance change tracking, enabling a comprehensive investigation of various cardiomyocyte traits. To demonstrate its versatility, we investigate the effects of four cardiac drugs with distinct pharmacological profiles on cardiomyocytes using this system. This platform provides a means for quantitatively and predictively assessing cardiac toxicity, which could be applied to conduct a comprehensive evaluation during the drug discovery process.
Assuntos
Sistemas Microfisiológicos , Miócitos Cardíacos , EletrodosRESUMO
Targeted microrobotic delivery within the circulatory system holds significant potential for medical theranostic applications. Existing delivery strategies of microrobots encounter challenges such as slow speed, limited navigation control, and dispersal under dynamic flow conditions. Furthermore, within the realm of microrobots, in vitro testing platforms often lack essential biological microenvironments, while in vivo studies conducted on animal models are constrained by limited detection resolution. In this study, we propose a multi-level magnetic delivery strategy that integrates a tethered microrobotic guidewire and untethered swimming microrobots. The amalgamation compensates for their inherent constraints, ensuring a robust and highly efficient delivery of microrobots under complex physiological conditions over extensive distances. Concurrently, a hierarchical vascular network encompassing engineered arteries/veins and capillary networks was constructed by integrating vasculogenesis and endothelial cell (EC) lining strategies, thereby providing an in vivo-like testing platform for microrobots. Experimental evidence demonstrates that the flexible microrobotic guidewire can be precisely directed to any entrance of the second-tier branches, with its inner lumen providing an "express lane" for rapid passage of microrobots through complex fluidic environments without direct contact. After release, dynamically assembled swarms could effectively locomote on the micro-topography of the EC-lined channel surface without becoming trapped and congregate within specified regions inside capillary lumens when guided collectively by a biologically safe magnetic field. Additionally, the superparamagnetic capabilities of microrobotic swarms ensure their dissolution into monodispersed entities upon withdrawal of the magnetic field, mitigating the risk of intravascular thrombosis. The hierarchical vascularized organ-on-a-chip platform establishes a comprehensive testing platform that integrates imaging, control, and a functional 3D microvascular environment, thereby enhancing its suitability for microrobotic applications encompassing targeted drug delivery, thrombus ablation, sensing and diagnosis, etc.
Assuntos
Magnetismo , Sistemas Microfisiológicos , Animais , Sistemas de Liberação de Medicamentos , Natação , Fenômenos MagnéticosRESUMO
In vitro organoid models, typically defined as 3D multicellular aggregates, have been extensively used as a promising tool in drug screening, disease progression research, and precision medicine. Combined with advanced microfluidics technique, organoid-on-a-chip can flexibly replicate in vivo organs within the biomimetic physiological microenvironment by accurately regulating different parameters, such as fluid conditions and concentration gradients of biochemical factors. Since engineered organ reconstruction has opened a new paradigm in biomedicine, innovative approaches are increasingly required in micro-nano fabrication, tissue construction, and development of pharmaceutical products. In this Perspective review, the advantages and characteristics of organoid-on-a-chip are first introduced. Challenges in current organoid culture, extracellular matrix building, and device manufacturing techniques are subsequently demonstrated, followed by potential alternative approaches, respectively. The future directions and emerging application scenarios of organoid-on-a-chip are finally prospected to further satisfy the clinical demands.
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Correction for 'Low-cost rapid prototyping and assembly of an open microfluidic device for a 3D vascularized organ-on-a-chip' by Qinyu Li et al., Lab Chip, 2022, https://doi.org/10.1039/d1lc00767j.
RESUMO
Reconstruction of 3D vascularized microtissues within microfabricated devices has rapidly developed in biomedical engineering, which can better mimic the tissue microphysiological function and accurately model human diseases in vitro. However, the traditional PDMS-based microfluidic devices suffer from the microfabrication with complex processes and usage limitations of either material properties or microstructure design, which drive the demand for easy processing and more accessible devices with a user-friendly interface. Here, we present an open microfluidic device through a rapid prototyping method by laser cutting in a cost-effective manner with high flexibility and compatibility. This device allows highly efficient and robust hydrogel patterning under a liquid guiding rail by spontaneous capillary action without the need for surface treatment. Different vascularization mechanisms including vasculogenesis and angiogenesis were performed to construct a 3D perfusable microvasculature inside a tissue chamber with various shapes under different microenvironment factors. Furthermore, as a proof-of-concept we have created a vascularized spheroid by placing a monoculture spheroid into the central through-hole of this device, which formed angiogenesis between the spheroid and microvascular network. This open microfluidic device has great potential for mass customization without the need for complex microfabrication equipment in the cleanroom, which can facilitate studies requiring high-throughput and high-content screening.
Assuntos
Dispositivos Lab-On-A-Chip , Microtecnologia , Humanos , Hidrogéis , Microvasos , Neovascularização PatológicaRESUMO
A practical system of B-ultrasonic is here introduced. By a special medical video card, the video image is digitized and captured dynamically or statically into computer. This system realizes a variety of functions such as the B-ultrasonic video image's acquisition and display, as well as the editing, processing, managing, storage, printing, It can build the database of patient's case history automatically. Together with other medical image workstation the system can be built as a PACS system of the hospital. And it can also act as an independent system.