Physical structuring of injectable polymeric systems to controllably deliver nanosized extracellular vesicles

Research output: Contribution to journalArticle

Authors

  • Niusha Nikravesh
  • Owen G. Davies
  • Ioannis Azoidis
  • Lucia Marani
  • Mark Turner
  • Cathal J. Kearney
  • Neil M. Eisenstein

Colleges, School and Institutes

External organisations

  • EMPA
  • Loughborough University
  • University Hospitals of Leicester NHS Trust
  • Royal College of Surgeons in Ireland
  • Trinity College Dublin

Abstract

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.

Bibliographic note

Nikravesh, N., Davies, O. G., Azoidis, I., Moakes, R. J. A., Marani, L., Turner, M., Kearney, C. J., Eisenstein, N. M., Grover, L. M., Cox, S. C., Adv. Healthcare Mater. 2019, 1801604. https://doi.org/10.1002/adhm.201801604

Details

Original languageEnglish
Article number1801604
JournalAdvanced Healthcare Materials
Volume8
Issue number9
Early online date6 Mar 2019
Publication statusPublished - 9 May 2019

Keywords

  • alginate, drug delivery, extracellular vesicles, hydrogel structuring