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Recently, surface engineering of NVs with membrane proteins from specific cell types has been shown to improve the biocompatibility of NVs and enable the integration of functional attributes. However, this type of biomimetic approach has not yet been explored using human neural cells for applications within the nervous system. Here, this paper optimizes and validates the scalable and reproducible production of two types of neuron\u2010targeting NVs, each with a distinct lipid formulation backbone suited to potential therapeutic cargo, by integrating membrane proteins that are unbiasedly sourced from human pluripotent stem\u2010cell\u2010derived neurons. The results establish that both endogenous and genetically engineered cell\u2010derived proteins effectively transfer to NVs without disruption of their physicochemical properties. NVs with neuron\u2010derived membrane proteins exhibit enhanced neuronal association and uptake compared to bare NVs. Viability of 3D neural sphere cultures is not disrupted by treatment, which verifies the utility of organoid\u2010based approaches as NV testing platforms. Finally, these results confirm cellular association and uptake of the biomimetic humanized NVs to neurons within rodent cranial nerves. In summary, the customizable NVs reported here enable next\u2010generation functionalized theranostics aimed to promote neuroregeneration.<\/jats:p>","DOI":"10.1002\/advs.202101437","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T02:56:17Z","timestamp":1628736977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Humanized Biomimetic Nanovesicles for Neuron Targeting"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7894-486X","authenticated-orcid":false,"given":"Assaf","family":"Zinger","sequence":"first","affiliation":[{"name":"Center for Musculoskeletal Regeneration Houston Methodist Research Institute Orthopedics and Sports Medicine Houston Methodist Hospital  Houston TX 77030 USA"},{"name":"Laboratory for Bioinspired Nano Engineering and Translational Therapeutics, Department of Chemical Engineering Technion\u2212Israel Institute of 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