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Rapid bone repair with the recruitment of CD206+M2-like macrophages using non-viral scaffold-mediated miR-133a inhibition of host cells

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posted on 13.05.2021, 14:54 by Irene M Castaño, Rosanne M Raftery, Gang ChenGang Chen, Brenton CavanaghBrenton Cavanagh, Brian Quinn, Garry DuffyGarry Duffy, Fergal O'BrienFergal O'Brien, Caroline CurtinCaroline Curtin
microRNAs offer vast therapeutic potential for multiple disciplines. From a bone perspective, inhibition of miR-133a may offer potential to enhance Runx2 activity and increase bone repair. This study aims to assess the therapeutic capability of antagomiR-133a delivery from collagen-nanohydroxyapatite (coll-nHA) scaffolds following cell-free implantation in rat calvarial defects (7 mm diameter). This is, to the best of our knowledge, the first report of successful in vivo antagomiR uptake in host cells of fully immunocompetent animals without distribution to other off-target tissues. Our results demonstrate the localized release of antagomiR-133a to the implant site at 1 week post-implantation with increased calcium deposits already evident in the antagomiR-133a loaded scaffolds at this early timepoint. This was followed by an approximate 2-fold increase in bone volume versus antagomiR-free scaffolds and a significant 10-fold increase over the empty defect controls, after just 4 weeks. An increase in host CD206 cells suggests an accelerated pro-remodeling response by M2-like macrophages accompanying bone repair with this treatment. Overall, this non-viral scaffold-mediated antagomiR-133a delivery platform demonstrates capability to accelerate bone repair in vivo – without the addition of exogenous cells – and underlines the role of M2 macrophage-like cells in directing accelerated bone repair. Expanding the repertoire of this platform to deliver alternative miRNAs offers exciting possibilities for a variety of therapeutic indications. Statement of Significance: microRNAs, small non-coding RNA molecules involved in gene regulation, may have potential as a new class of bone healing therapeutics as they can enhance the regenerative capacity of bone-forming cells. We developed a collagen-nanohydroxyapatite-microRNA scaffold system to investigate whether miR133a inhibition can enhance osteogenesis in rat MSCs and ultimately accelerate endogenous bone repair by host cells in vivo without pre-seeding cells prior to implantation. Overall, this off-the-shelf, non-viral scaffold-mediated antagomiR-133a delivery platform demonstrates capability to accelerate bone repair in vivo – without the requirement of exogenous cells – and highlights the role of CD206 M2 macrophage-like cells in guiding accelerated bone repair. Translating the repertoire of this platform to deliver alternative miRNAs offers exciting possibilities for a vast myriad of therapeutic indications. + +

Funding

Science Foundation Ireland (SFI) Research Frontiers Programme (Grant no. 11/RFP/ENM/3053)

Advanced Materials and Bioengineering Research (AMBER) Center through SFI (SFI/12/RC/2278)

European Research Council under the European Community’s Horizon 2020 Framework Programme/ERC Grant agreement no. 665777 (miRaColl) and no. 788753 (ReCaP)

History

Comments

The original article is available at https://www.sciencedirect.com

Published Citation

Castaño IM, Raftery RM, Chen G, Cavanagh B, Quinn B, Duffy GP, O'Brien FJ, Curtin CM. Rapid bone repair with the recruitment of CD206+M2-like macrophages using non-viral scaffold-mediated miR-133a inhibition of host cells. Acta Biomaterialia. 2020;109:267-279.

Publication Date

3 April 2020

PubMed ID

32251781

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • Physiology and Medical Physics
  • RCSI Tissue Engineering Group (TERG)
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Chemistry and Pharmaceutical Sciences
  • Cancer
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

Elsevier

Version

  • Accepted Version (Postprint)