Critical Challenges and Future Direction in Extracellular Vesicle Research and Commercialization

Abstract

Exosomes are nanoscale extracellular vesicles that have emerged as critical mediators of intercellular communication and hold significant promise as diagnostic biomarkers and therapeutic drug delivery system. This review provides a comprehensive overview of the field, covering the historical background of exosome research, classification criteria delineating distinctions between natural exosomes and artificial exosomes. Key diagnostic and therapeutic applications are highlighted alongside critical limitations and regulatory hurdles of natural exosomes, such as batch-to-batch variability, content heterogeneity, and scalability that impede clinical translation. Engineering strategies for exosome fabrication are systematically examined, encompassing top-down approaches (modifying source cells to engineer natural exosomes) and bottom-up approaches (constructing artificial exosomes de novo). Emerging microfluidic bottom-up fabrication techniques are emphasized as promising solutions for improving scalability and uniformity. Furthermore, the review highlights the emerging role of artificial intelligence-assisted design in the development of customized synthetic artificial exosomes. Together, these discussions address major challenges in the field and propose future directions to accelerate the development and clinical translation of exosome-based therapeutics.