Table 2.

A list of large-scale EV generation methods

Type of generated EV	Generation method	Generation mechanism	References
Artificial EV generation	Nitrogen cavitation	Nitrogen gas-mediated bubble formation within the cells	[46, 47]
	Extrusion via porous membrane	Pushing cell through porous membrane using extruder	[48]
	Sonication	Cell rupture with hypotonic lysis, mechanical disruption and formation of artificial EV with sonication	[50]
	High pH solution and sonication	Alkaline solution to dissolve cellular membrane. Following pH neuralization and sonication	[51]
	Artificial EV synthesis	Plasma membrane protein extraction and assembly with cholesterol and synthetic choline-based phospholipids	[52, 53]
Large scale natural EV generation	Dithiothreitol, paraformaldehyde	Sulfhydryl-blocking	[43]
	Stimulation of red blood cells	Treatment of calcium ionophore A23187	[54]
	Using bioreactor	Maximizing cell culture efficiency on large surface area	[56–58]
	Using 3D scaffold in bioreactors	Complex architecture combined with flow or mechanical stimulation	[60, 61]
	Cellular nanoporation	A transient electrical stimulation	[62]