Extracellular vesicles (EVs), a diverse population of bilayer lipid-membrane vesicles secreted by cells, have emerged as ideal drug carriers due to their efficient cellular uptake and targeted delivery capabilities. Advancements in medical and bioengineering collaborations have enabled EVs to be engineered for specific marker expression or therapeutic cargo transport, positioning them as a promising modality for treating cancer, neurological disorders, cardiovascular diseases, and beyond. EV-based drug delivery strategies offer distinct advantages, including facilitation of intercellular communication and immune modulation, high biocompatibility and stability, the ability to traverse the blood-brain barrier, and potential synergistic interactions with encapsulated therapeutics to enhance efficacy. This review explores EV isolation and scalable production, emphasizing cost-effective and reproducible manufacturing strategies, cargo-loading methodologies, and therapeutic applications. Additionally, the current landscape of EV-based targeted drug delivery, clinical translation prospects, and prevailing challenges are examined to provide a comprehensive perspective on their potential in drug delivery systems.

In the 21st century, research on extracellular vesicles (EVs) has made remarkable advancements. Recently, researchers have uncovered the exceptional biological features of EVs, highlighting their prospective use as therapeutic targets, biomarkers, innovative drug delivery systems, and standalone therapeutic agents. Currently, mesenchymal stem cells stand out as the most potent source of EVs for clinical applications in tissue engineering and regenerative medicine. Owing to their accessibility and capability of undergoing numerous differentiation inductions, dental stem cell-derived EVs (DSC-EVs) offer distinct advantages in the field of tissue regeneration. Nonetheless, it is essential to note that unmodified EVs are currently unsuitable for use in the majority of clinical therapeutic scenarios. Considering the high feasibility of engineering EVs, it is imperative to modify these EVs to facilitate the swift translation of theoretical knowledge into clinical practice. The review succinctly presents the known biotherapeutic effects of odontogenic EVs and the underlying mechanisms. Subsequently, the current state of functional cargo loading for engineered EVs is critically discussed. For enhancing EV targeting and in vivo circulation time, the review highlights cutting-edge engineering solutions that may help overcome key obstacles in the clinical application of EV therapeutics. By presenting innovative concepts and strategies, this review aims to pave the way for the adaptation of DSC-EVs in regenerative medicine within clinical settings.