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Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting over five million people globally and has no established cure. Current AD-related treatments only alleviate cognitive and behavioral symptoms and do not address disease onset or progression, underlining the unmet need to create an effective, innovative AD therapeutic. Extracellular vesicles (EVs) have emerged as a new class of nanotherapeutics. These secreted, lipid-bound cellular signaling carriers show promise for potential clinical applications for neurodegenerative diseases like AD. Additionally, analyzing contents and characteristics of patient-derived EVs may address the unmet need for earlier AD diagnostic techniques, informing physicians of altered genetic expression or cellular communications specific to healthy and diseased physiological states. There are numerous recent advances in regenerative medicine using EVs and include bioengineering perspectives to modify EVs, target glial cells in neurodegenerative diseases like AD, and potentially use EVs to diagnose and treat AD earlier. This article is categorized under: Neurological Diseases > Biomedical Engineering Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Stem Cells and Development.

Multiple sclerosis (MS) is a debilitating degenerative disease characterized by an immunological attack on the myelin sheath leading to demyelination and axon degeneration. Mesenchymal stem/stromal cells (MSCs) and secreted extracellular vesicles (EVs) have become attractive targets as therapies to treat neurodegenerative diseases such as MS due to their potent immunomodulatory and regenerative properties. The placenta is a unique source of MSCs (PMSCs), demonstrates "fetomaternal" tolerance during pregnancy, and serves as a novel source of MSCs for the treatment of neurodegenerative diseases. PMSCs and PMSC-EVs have been shown to promote remyelination in animal models of MS, however, the molecular mechanisms by which modulation of autoimmunity and promotion of myelination occurs have not been well elucidated. The current review will address the molecular mechanisms by which PMSC-EVs can promote remyelination in MS.

Extracellular vesicle (EV)-based technologies represent a new advancement for disease treatment. EVs can be administered systemically, injected into the injury site directly, or applied locally in conjunction with bioengineered implantable scaffolds. Matrix-bound vesicles (MBVs), a special class of vesicles localized in association with the extracellular matrix (ECM), have been identified as critical bioactive factors and shown to mediate significant regenerative functions of ECM scaffolds. Loading EVs onto bioscaffolds to mimic the MBV-ECM complex has been shown superior to EV bolus injection in recent in vivo studies, such as in providing enhanced tissue regeneration, EV retention rates, and healing efficacy. Different types of natural biomaterials, synthetic polymers, and ceramics have been developed for EV loading, and these EV functionalized biomaterials have been applied in different areas for disease treatment. The EV functionalized scaffolds can be designed to be biodegradable, off-the-shelf biomaterials as a delivery vehicle for EVs. Overall, the bioengineered EV-loaded bioscaffolds represent a promising approach for cell-free treatment in clinical applications.