Back
Hydrogel-based delivery of antimiR-221 enhances cartilage regeneration by endogenous cells.
Journal article

Hydrogel-based delivery of antimiR-221 enhances cartilage regeneration by endogenous cells.

  • Lolli A Department of Orthopaedics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Sivasubramaniyan K Department of Orthopaedics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Vainieri ML Department of Orthopaedics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; AO Research Institute, Davos, Switzerland.
  • Oieni J Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
  • Kops N Department of Orthopaedics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Yayon A ProCore Ltd., Weizmann Science Park, Nes Ziona, Israel.
  • van Osch GJVM Department of Orthopaedics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. Electronic address: g.vanosch@erasmusmc.nl.
Show more…
  • 2019-08-02
Published in:
  • Journal of controlled release : official journal of the Controlled Release Society. - 2019
Cartilage
Endogenous cells
Hydrogel
Regenerative medicine
microRNA
Aged
Animals
Cartilage, Articular
Cells, Cultured
Chondrogenesis
Drug Delivery Systems
Female
Fibrin
Humans
Hyaluronic Acid
Hydrogels
Mesenchymal Stem Cells
Mice
MicroRNAs
Middle Aged
Regeneration
English Articular cartilage is frequently injured by trauma or osteoarthritis, with limited and inadequate treatment options. We investigated a new strategy based on hydrogel-mediated delivery of a locked nucleic acid microRNA inhibitor targeting miR-221 (antimiR-221) to guide in situ cartilage repair by endogenous cells. First, we showed that transfection of antimiR-221 into human bone marrow-derived mesenchymal stromal cells (hMSCs) blocked miR-221 expression and enhanced chondrogenesis in vitro. Next, we loaded a fibrin/hyaluronan (FB/HA) hydrogel with antimiR-221 in combination or not with lipofectamine carrier. FB/HA strongly retained functional antimiR-221 over 14 days of in vitro culture, and provided a supportive environment for cell transfection, as validated by flow cytometry and qRT-PCR analysis. Seeding of hMSCs on the surface of antimiR-221 loaded FB/HA led to invasion of the hydrogel and miR-221 knockdown in situ within 7 days. Overall, the use of lipofectamine enhanced the potency of the system, with increased antimiR-221 retention and miR-221 silencing in infiltrating cells. Finally, FB/HA hydrogels were used to fill defects in osteochondral biopsies that were implanted subcutaneously in mice. FB/HA loaded with antimiR-221/lipofectamine significantly enhanced cartilage repair by endogenous cells, demonstrating the feasibility of our approach and the need to achieve highly effective in situ transfection. Our study provides new evidence on the treatment of focal cartilage injuries using controlled biomaterial-mediated delivery of antimicroRNA for in situ guided regeneration.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/278783
Statistics
Document views: 55 File downloads: