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In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint

1
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria
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Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
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AO Research Institute Davos, 7270 Davos Platz, Switzerland
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Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
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ETHRIS GmbH, 82152 Planegg, Germany
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20Med Therapeutics B.V., Galileiweg 8, 2333BD Leiden, The Netherlands
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Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland
*
Authors to whom correspondence should be addressed.
Authors contributed equally.
Academic Editor: Tae-Jong Yoon
Biomedicines 2021, 9(7), 794; https://doi.org/10.3390/biomedicines9070794
Received: 24 May 2021 / Revised: 30 June 2021 / Accepted: 5 July 2021 / Published: 8 July 2021
(This article belongs to the Section Biomedical Materials and Nanomedicine)
Biodegradable and bioresponsive polymer-based nanoparticles (NPs) can be used for oligonucleotide delivery, making them a promising candidate for mRNA-based therapeutics. In this study, we evaluated and optimized the efficiency of a cationic, hyperbranched poly(amidoamine)s-based nanoparticle system to deliver tdTomato mRNA to primary human bone marrow stromal cells (hBMSC), human synovial derived stem cells (hSDSC), bovine chondrocytes (bCH), and rat tendon derived stem/progenitor cells (rTDSPC). Transfection efficiencies varied among the cell types tested (bCH 28.4% ± 22.87, rTDSPC 18.13% ± 12.07, hBMSC 18.23% ± 14.80, hSDSC 26.63% ± 8.81) and while an increase of NPs with a constant amount of mRNA generally improved the transfection efficiency, an increase of the mRNA loading ratio (2:50, 4:50, or 6:50 w/w mRNA:NPs) had no impact. However, metabolic activity of bCHs and rTDSPCs was significantly reduced when using higher amounts of NPs, indicating a dose-dependent cytotoxic response. Finally, we demonstrate the feasibility of transfecting extracellular matrix-rich 3D cell culture constructs using the nanoparticle system, making it a promising transfection strategy for musculoskeletal tissues that exhibit a complex, dense extracellular matrix. View Full-Text
Keywords: transfection; bioresponsive polymer-based nanoparticles; joint therapies; therapeutic mRNA; biologicals transfection; bioresponsive polymer-based nanoparticles; joint therapies; therapeutic mRNA; biologicals
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MDPI and ACS Style

Sturm, L.; Schwemberger, B.; Menzel, U.; Häckel, S.; Albers, C.E.; Plank, C.; Rip, J.; Alini, M.; Traweger, A.; Grad, S.; Basoli, V. In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint. Biomedicines 2021, 9, 794. https://doi.org/10.3390/biomedicines9070794

AMA Style

Sturm L, Schwemberger B, Menzel U, Häckel S, Albers CE, Plank C, Rip J, Alini M, Traweger A, Grad S, Basoli V. In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint. Biomedicines. 2021; 9(7):794. https://doi.org/10.3390/biomedicines9070794

Chicago/Turabian Style

Sturm, Lisa, Bettina Schwemberger, Ursula Menzel, Sonja Häckel, Christoph E. Albers, Christian Plank, Jaap Rip, Mauro Alini, Andreas Traweger, Sibylle Grad, and Valentina Basoli. 2021. "In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint" Biomedicines 9, no. 7: 794. https://doi.org/10.3390/biomedicines9070794

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