Physical structuring of injectable polymeric systems to controllably deliver nanosized extracellular vesicles
journal contributionposted on 03.04.2019, 08:45 by Niusha Nikravesh, Owen DaviesOwen Davies, Ioannis Azoidis, Richard J. Moakes, Lucia Marani, Mark Turner, Cathal J. Kearney, Neil M. Eisenstein, L.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.
For funding, S.C.C., O.G.D., and N.N. recognize the University of Birmingham's MRC Confidence in Concept scheme and O.G.D. the EPSRC E‐TERM Landscape Fellowship. I.A. acknowledges the School of Chemical Engineering, University of Birmingham for doctoral funding. C.J.K. thanks the EU for funding under ERC Starting Grant (Proj. ref: 758064) and Science Foundation Ireland (SFI) under Grant no. SFI/12/RC/2278 (the AMBER Centre). L.M. acknowledges funding from the EPSRC‐NIHR HTC Partnership Award: UNIFY Plus. M.T. was supported by the NIHR Leicester Biomedical Research Centre.
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