A Combination of Flexible Modified Plant Virus Nanoparticles Enables Additive Effects Resulting in Improved Osteogenesis

Advanced Healthcare Materials, vol. 13, pp. e2304243

Abstract

Plant virus nanoparticles (VNPs) genetically engineered to present osteogenic cues provide a promising method for biofunctionalizing hydrogels in bone tissue engineering. Flexible Potato virus X (PVX) nanoparticles substantially enhance the attachment and differentiation of human mesenchymal stem cells (hMSCs) by presenting the RGD motif, hydroxyapatite-binding peptide (HABP), or consecutive polyglutamates (E8) in a concentration-dependent manner. Therefore, it is hypothesized that Tobacco mosaic virus nanoparticles, which present 1.6 times more functional peptides than PVX, will meliorate such an impact. This study hypothesizes that cultivating hMSCs on a surface coated with a combination of two VNPs presenting peptides for either cell attachment or mineralization can achieve additionally enhancing effects on osteogenesis. Calcium minerals deposited by differentiating hMSCs increases two to threefold for this combination, while the Alkaline Phosphatase activity of hMSCs grown on the PVX-RGD/PVX-HABP-coated surface significantly surpasses any other VNP combination. Superior additive effects are observed for the first time by employing a combination of VNPs with varying functionalities. It is found that the flexible VNP geometry plays a more critical role than the concentration of functional peptides. In conclusion, various peptide-presenting plant VNPs exhibit an additive enhancing effect offering significant potential for effectively functionalizing cell-containing hydrogels in bone tissue engineering.

Authors 8

1. Juliane Schuphan corresponding Aachen Institute for Molecular Biotechnology

   RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Biotechnology RWTH Aachen University Worringerweg 1 52074 Aachen Germany

   Institute for Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany

2. Natalija M. Stojanovic Aachen Department of Dental Materials and Biomaterials Research

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Dental Materials and Biomaterials Research RWTH Aachen University Hospital Pauwelsstrasse 30 52074 Aachen Germany

   Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany

3. Yingying Lin Aachen Department of Dental Materials and Biomaterials Research

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Dental Materials and Biomaterials Research RWTH Aachen University Hospital Pauwelsstrasse 30 52074 Aachen Germany

   Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany

4. Eva Miriam Buhl Aachen Institute of Pathology Electron Microscopy Facility Electron Microscopy Facility Institute of Pathology

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Electron Microscopy Facility Institute of Pathology RWTH Aachen University Hospital Pauwelsstrasse 30 52074 Aachen Germany

   Electron Microscopy Facility, Institute of Pathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany

5. Sanja Aveic Aachen Department of Dental Materials and Biomaterials Research

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Dental Materials and Biomaterials Research RWTH Aachen University Hospital Pauwelsstrasse 30 52074 Aachen Germany

   Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany

6. Ulrich Commandeur Aachen Institute for Molecular Biotechnology

   RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Biotechnology RWTH Aachen University Worringerweg 1 52074 Aachen Germany

   Institute for Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany

7. Stefan Schillberg Aachen Institute for Molecular Biotechnology

   RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Biotechnology RWTH Aachen University Worringerweg 1 52074 Aachen Germany

   Institute for Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany

8. Horst Fischer corresponding Aachen Department of Dental Materials and Biomaterials Research

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Dental Materials and Biomaterials Research RWTH Aachen University Hospital Pauwelsstrasse 30 52074 Aachen Germany

   Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany