Extracellular Vesicle Mimetics: Preparation from Top‐Down Approaches and Biological Functions

Abstract

Extracellular vesicles (EVs) have attracted attention as delivery vehicles due to their structure, composition, and unique properties in regeneration and immunomodulation. However, difficulties during production and isolation processes of EVs limit their large‐scale clinical applications. EV mimetics (EVMs), prepared via top‐down strategies that improve the yield of nanoparticles while retaining biological properties similar to those of EVs have been used to address these limitations. Herein, the preparation of EVMs is reviewed and their characteristics in terms of structure, composition, targeting ability, cellular uptake mechanism, and immunogenicity, as well as their strengths, limitations, and future clinical application prospects as EV alternatives are summarized.

Preparation of therapy-grade extracellular vesicles from adipose tissue to promote diabetic wound healing

“…This demonstrated that EVs prepared by the three methods represented combinations of EVs and non-EV components, and their specific composition requires further identification. It is also possible that the mechanical process of opening cells and intercellular spaces to capture EVs also chopped the cells into EV-mimetics using shear forces ( Du et al, 2022 ), which may also explain why mAT-EVs exhibited highest GM130 expression. The contamination with non-EV material may also be attributed to usage of the ultrafiltration method.…”

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration

“…2 C). EVM preparation methods (See REVIEW [ 44 ] for details) can achieve yields hundreds of times higher than those of EVs while retaining similar bioactive functions [ 44 ]. EVM can be broadly classified into three different principles, which can be chosen according to different needs: direct cell preparation, preparation after removal of cytoplasm and nucleus, or fusion with cell-secreted EVs using liposomes [ 44 ].…”

“…EVM preparation methods (See REVIEW [ 44 ] for details) can achieve yields hundreds of times higher than those of EVs while retaining similar bioactive functions [ 44 ]. EVM can be broadly classified into three different principles, which can be chosen according to different needs: direct cell preparation, preparation after removal of cytoplasm and nucleus, or fusion with cell-secreted EVs using liposomes [ 44 ]. Different preparation methods affect the surface markers and cargoes of EVM, depending on which of its properties the investigators want to exploit, bioactivity or drug-carrying capacity [ 44 ].…”

“…Adapted reprinted with permission from Ref. [ 44 ], Copyright © 2022 Wiley-VCH GmbH (License number:5,440,800,929,863). …”

Polymers in Engineering Extracellular Vesicle Mimetics: Current Status and Prospective

“…Alternatively, the “bottom-up” method can be used to create liposomes by selecting specific lipids and gradually fusing them into a particular size [ 74 ]. Compared to the top-down approach, the bottom-up method enables more precise control of the liposome structure and produces a more definite surface modification effect, making it more conducive to the industrialization of liposome drugs [ 75 , 76 , 77 ]. However, liposome instability is a crucial issue when preparing clinical drugs.…”