Engineering vascularised organoid-on-a-chip: strategies, advances and future perspectives.

In recent years, advances in microfabrication technology and tissue engineering have propelled the development of a novel drug screening and disease modelling platform known as organoid-on-a-chip. This platform integrates organoids and organ-on-a-chip technologies, emerging as a promising approach for in vitro modelling of human organ physiology. Organoid-on-a-chip devices leverage microfluidic systems to simulate the physiological microenvironment of specific organs, offering a more dynamic and flexible setting that can mimic a more comprehensive human biological context. However, the lack of functional vasculature has remained a significant challenge in this technology. Vascularisation is crucial for the long-term culture and in vitro modelling of organoids, holding important implications for drug development and personalised medical approaches. This review provides an overview of research progress in developing vascularised organoid-on-a-chip models, addressing methods for in vitro vascularisation and advancements in vascularised organoids. The aim is to serve as a reference for future endeavors in constructing fully functional vascularised organoid-on-a-chip platforms.

Multifunctional cardiac microphysiological system based on transparent ITO electrodes for simultaneous optical measurement and electrical signal monitoring.

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.

Multi-level magnetic microrobot delivery strategy within a hierarchical vascularized organ-on-a-chip.

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.

Organoid-on-a-chip: Current challenges, trends, and future scope toward medicine.

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.

Constructing a Rigid-and-Flexible Twin-Stage Gradient Interphase through Starlike Copolymer Coating on Carbon Fibers: A Route for Enhancing Interfacial Properties of Composites.

A rigid-and-flexible interphase was established by a starlike copolymer (Pc-PGMA/Pc) consisting of one tetraaminophthalocyanine (TAPc) core with four TAPc-difunctionalized poly(glycidyl methacrylate) (PGMA) arms through the surface modification of carbon fibers (CFs) and compared with various interphases constructed by TAPc and TAPc-connected PGMA (Pc-PGMA). The increase in the content of N-C═O showed that PGMA/Pc branches were successfully attached onto the CF-(Pc-PGMA/Pc) surface, exhibiting concavo-convex microstructures with the highest roughness. Through adhesive force spectroscopy by atomic force microscopy (AFM) with peak force quantitative nanomechanical mapping (PF-QNM) mode and visualization of the relative distribution of TAPc/PGMA via a Raman spectrometer, a rigid interphase with highly cross-linked TAPc and a flexible layer from PGMA arms as the soft segment were separately detected in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. The rigid-and-flexible interphase in the CF-(Pc-PGMA/Pc)/EP composite provided excellent stress-transfer capability by the rigid inner modulus intermediate layer and energy absorption efficiency from the flexible outer layer, which contributed to 64.6 and 61.8% increment of transverse fiber bundle test (TFBT) strength, and 33.8 and 40.6% enhancement in interfacial shear strength (IFSS) in comparison with those of CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. Accordingly, schematic models of the interphase reinforcing mechanism were proposed. The interfacial failures in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites were derived from the rigid interphase without effective relaxation of interfacial stress and soft interphase with excessive fiber-matrix interface slippage, respectively. The cohesive failure in the CF-(Pc-PGMA/Pc)/EP composite was attributed to the crack deflection through the balance of the modulus and deformability from the twin-stage gradient intermediate layer.