Organ phantoms are widely used for evaluating medical technologies, training clinical practitioners, as well as surgical planning. In the context of cardiovascular disease, a patient-specific cardiac phantom can play an important role for interventional cardiology procedures. However, phantoms with complicated structures are difficult to fabricate by conventional manufacturing methods. The emergence of three-dimensional (3D) printing with soft materials provides the opportunity to produce phantoms with complex geometries and realistic properties. In this work, the aim was to explore the use of a direct 3D printing technique to produce multimodal imaging cardiac phantoms and to test the physical properties of the new materials used, namely the Poro-Lay series and TangoPlus. The cardiac phantoms were first modeled using real data segmented from a patient chest computer tomography (CT) scan and then printed with the novel materials. They were then tested quantitatively in terms of stiffness and ultrasound (US) acoustic values and qualitatively with US, CT, and magnetic resonance imaging systems. From the stiffness measurements, Lay-fomm 40 had the closest Young's modulus to real myocardium with an error of 29-54%, while TangoPlus had the largest difference. From the US acoustics measurements, Lay-fomm 40 also demonstrated the closest soft tissue-mimicking properties with both the smallest attenuation and impedance differences. Furthermore, the imaging results show that the phantoms are compatible with multiple imaging modalities and thus have potential to be used for interventional procedure simulation and testing of novel interventional devices. In conclusion, direct 3D printing with Poro-Lay and TangoPlus is a promising method for manufacture of multimodal imaging phantoms with complicated structures, especially for soft patient-specific phantoms.

In recent years, extracellular vesicles (EVs) have emerged as promising biomarkers, cell-free therapeutic agents, and drug delivery carriers. Despite their great clinical potential, poor yield and unscalable production of EVs remain significant challenges. When using 3D culture methods, such as scaffolds and bioreactors, large numbers of cells can be expanded and the cell environment can be manipulated to control the cell phenotype. This has been employed to successfully increase the production of EVs as well as to enhance their therapeutic effects. The physiological relevance of 3D cultures, such as spheroids, has also provided a strategy for understanding the role of EVs in the pathogenesis of several diseases and to evaluate their role as tools to deliver drugs. Additionally, 3D culture methods can encapsulate EVs to achieve more sustained therapeutic effects as well as prevent premature clearance of EVs to enable more localised delivery and concentrated exosome dosage. This review highlights the opportunities and drawbacks of different 3D culture methods and their use in EV research.