Therapeutic biomaterials based on extracellular vesicles: classification of bio-engineering and mimetic preparation routes

Extracellular vesicles (EVs) are emerging as novel theranostic tools. Limitations related to clinical uses are leading to a new research area on design and manufacture of artificial EVs. Several strategies have been reported in order to produce artificial EVs, but there has not yet been a clear criterion by which to differentiate these novel biomaterials. In this paper, we suggest for the first time a systematic classification of the terms used to build up the artificial EV landscape, based on the preparation method. This could be useful to guide the derivation to clinical trial routes and to clarify the literature. According to our classification, we have reviewed the main strategies reported to date for their preparation, including key points such as: cargo loading, surface targeting strategies, purification steps, generation of membrane fragments for the construction of biomimetic materials, preparation of synthetic membranes inspired in EV composition and subsequent surface decoration.