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

Nikravesh N; Davies OG; Azoidis I; Moakes RJA; Marani L; Turner M; Kearney CJ; Eisenstein NM; Grover LM; Cox SC

doi:10.1002/adhm.201801604

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Journal article

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

Nikravesh N Laboratory for Particles-Biology Interactions, Swiss Federal Laboratories for Materials Science and Technology (Empa), St. Gallen, 9014, Switzerland.
Davies OG School of Sport, Exercise and Health Sciences, Loughborough University, Epinal Way, LE11 3TU, UK.
Azoidis I School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Moakes RJA School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Marani L School of Sport, Exercise and Health Sciences, Loughborough University, Epinal Way, LE11 3TU, UK.
Turner M School of Sport, Exercise and Health Sciences, Loughborough University, Epinal Way, LE11 3TU, UK.
Kearney CJ Department of Anatomy, Kearney Lab & Tissue Engineering Research Group (TERG), Royal College of Surgeons in Ireland (RCSI), 123 St Stephen's Green, Dublin, D02 YN77, Ireland.
Eisenstein NM School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Grover LM School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Cox SC School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

2019-03-07

Published in:

Advanced healthcare materials. - 2019

Microscopy, Electron, Transmission

English 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.

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