Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, have emerged as central mediators of intercellular communication, with key roles in physiological homeostasis and major diseases such as cancer and regenerative disorders. Their unique advantages over cell-based therapies, particularly in terms of stability, storage, and safety, have driven a rapid expansion of clinical interest. However, the development of EV-based therapeutics has been critically hindered by the lack of robust, scalable, and high-yield production technologies. Conventional approaches rely on low endogenous secretion rates or modest induction strategies, resulting in limited yields, long production times, and high material costs. Moreover, existing systems are not adapted to advanced and physiologically relevant cellular models, such as organoids, despite clear evidence that the therapeutic identity and functional properties of EVs are strongly dependent on the state and environment of their parental cells. This is particularly limiting in the context of pluripotent stem cells, which are becoming a cornerstone of next-generation therapies but remain largely underexploited for EV production, especially in organoid configurations.
Within this context, EVoid has addressed these critical technological and conceptual bottlenecks by establishing a novel paradigm for EV bioproduction. The project demonstrated the feasibility of integrating the formation of physiologically relevant 3D cellular constructs, spheroids and organoids, with high-throughput EV production in a single hydrodynamic platform. This approach enabled a significant increase in production yield while reducing processing time and cell material requirements, and simultaneously improved the biological relevance and specificity of the produced EVs. By bridging advanced cell culture systems with scalable biomanufacturing, EVoid provides a coherent response to the unmet need for efficient and versatile EV production technologies. The results position this technology as a potential enabler for the industrialisation of EV-based therapies and for the development of next-generation biologics with enhanced functional properties, thereby contributing to the broader advancement of regenerative medicine, precision therapeutics, and biomedical innovation.
In addition, the project contributed to the validation of a novel EV characterisation technique combining interferometric scattering and holographic tracking, enabling highly sensitive detection of very small particles together with quantitative measurements of size, scattering properties, and concentration.
