Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles.

Nikravesh, Niusha; Davies, Owen G.; Azoidis, Ioannis; Moakes, Richard JA; Marani, Lucia; Turner, Mark; Kearney, Cathal J.; Eisenstein, Neil M.; Grover, Liam M.; Cox, Sophie C.

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Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles.

Version 3 2022-05-24, 10:55

Version 2 2021-10-13, 08:52

Version 1 2019-11-23, 12:12

journal contribution

posted on 2019-11-22, 15:07 authored by Niusha Nikravesh, Owen G. Davies, Ioannis Azoidis, Richard JA Moakes, Lucia Marani, Mark Turner, Cathal J. Kearney, Neil M. Eisenstein, Liam M. Grover, Sophie C. Cox

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell-therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet-like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs.

Funding

University of Birmingham’s MRC Confidence in Concept scheme. EPSRC E-TERM Landscape Fellowship. School of Chemical Engineering, University of Birmingham for doctoral funding. ERC Starting Grant (Proj. ref: 758064). Science Foundation Ireland (SFI) under Grant no. SFI/12/RC/2278 (the AMBER Centre). EPSRC-NIHR HTC Partnership Award: UNIFY Plus. NIHR Leicester Biomedical Research Centre.

History

Comments

"This is the peer reviewed version of the following article:, Nikravesh N, Davies OG, Azoidis I, Moakes RJA, Marani L, Turner M, Kearney CJ, Eisenstein NM, Grover LM, Cox SC. Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles. Advanced Healthcare Materials. 2019;8(9):e1801604., which has been published in final form at [Link to final article using the https://doi.org/10.1002/adhm.201801604. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."

Published Citation

Nikravesh N, Davies OG, Azoidis I, Moakes RJA, Marani L, Turner M, Kearney CJ, Eisenstein NM, Grover LM, Cox SC. Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles. Advanced Healthcare Materials. 2019;8(9):e1801604.