Engineered Potato virus X nanoparticles support hydroxyapatite nucleation for improved bone tissue replacement

Lauria, Ines; Dickmeis, Christina; Röder, Juliane; Beckers, Markus; Rütten, Stephan; Lin, Ying; Commandeur, Ulrich; Fischer, Horst

doi:10.1016/j.actbio.2017.08.039

Cited by 26 publications

(51 citation statements)

References 67 publications

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“…Similarly, Dickmeis et al (2017) took advantage of the filamentous properties of Potato virus X to present mineralization-inducing (MIP) and integrin binding motif (RGD) peptides on its surface. Virus particles isolated from plants were used to support hydroxyapatite crystal nucleation, indicating that plant virus helical nanoparticles show potential for bone tissue substitutes [ 52 ].…”

Section: Other Applications For Plant Virus Nanoparticlesmentioning

confidence: 99%

Repurposing Plant Virus Nanoparticles

Hefferon

2018

Vaccines

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Plants have been explored for many years as inexpensive and versatile platforms for the generation of vaccines and other biopharmaceuticals. Plant viruses have also been engineered to either express subunit vaccines or act as epitope presentation systems. Both icosahedral and helical, filamentous-shaped plant viruses have been used for these purposes. More recently, plant viruses have been utilized as nanoparticles to transport drugs and active molecules into cancer cells. The following review describes the use of both icosahedral and helical plant viruses in a variety of new functions against cancer. The review illustrates the breadth of variation among different plant virus nanoparticles and how this impacts the immune response.

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Section: Other Applications For Plant Virus Nanoparticlesmentioning

confidence: 99%

Repurposing Plant Virus Nanoparticles

Hefferon

2018

Vaccines

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“…19 Potato virus X (PVX) engineered to present mineralization-inducing (MIP) and RGD peptides on the surface of PVX VNPs enhanced cell adhesion, osteoblast differentiation, and mineralization in vitro. 20 The common theme of these studies was that plant VNP-modified materials could strongly promote osteoinduction in vitro. However, there has been a lack of investigation on how would these materials perform in vivo and whether they could impact osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

<p>Tobacco Mosaic Viral Nanoparticle Inhibited Osteoclastogenesis Through Inhibiting mTOR/AKT Signaling</p>

Shan

Suonan

et al. 2020

IJN

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Introduction: Tobacco mosaic virus-based nanoparticles (TMV VNPs) were previously shown to promote osteogenic differentiation in vitro. This study aims to investigate whether and how TMV VNPs impact on osteoclastogenesis in vitro and bone injury healing in vivo. Methods: Raw264.7 cells were cultured in osteoclastogenic medium in culture plates coated with or without TMV and TMV-RGD1 VNPs, followed by TRAP staining, RT-qPCR and WB assessing expression of osteoclastogenic marker genes, and immunofluorescence assessing NF-κB activation. TMV and TMV-RGD1-modified hyaluronic acid hydrogel were used to treat mouse tibial bone injury. Bone injury healing was checked by micro-CT and Masson staining. Results: TMV and TMV-RGD1 VNPs significantly inhibited osteoclast differentiation and downregulated the expression of osteoclastogenic marker genes Ctr, Ctsk, Mmp-9, Rank, and Trap. Moreover, TMV and TMV-RGD1 VNPs inhibited NF-κB p65 phosphorylation and nuclear translocation, as well as activation of mTOR/AKT signaling pathway. TMV and TMV-RGD1-modified HA hydrogel strongly promoted mouse tibial bone injury with increased bone mass compared to plain HA hydrogel. The amount of osteoclasts was significantly reduced in TMV and TMV-RGD1 treated mice. TMV-RGD1 was more effective than TMV in inhibiting osteoclast differentiation and promoting bone injury repair. Discussion: These data demonstrated the great potential of TMV VNPs to be developed into biomaterial for bone injury repair or replacement.

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“…Furthermore, a high local concentration of peptides on small scaffolds like silk backbones or biocompatible VNPs favor a greater control over mineralization. [17,43] The spatial organization and constitution of the created artificial ECM will greatly influence the cell responses and mineralization potential. [44] Bone ECM consists predominantly of collagen type I, and only ≈5% are NCPs such as osteocalcin, osteopontin, osteonectin, and fibronectin.…”

Section: Vnp Production and Mineralization In Vitromentioning

confidence: 99%

“…To enhance cell attachment with PVX, our previous study showed an improvement using PVX engineering with RGD peptides. [17] Studies have demonstrated osteogenic differentiation of MSCs on virus-coated substrates, which generate nanotopographical signals and/or chemical cues that alter the cell behavior, including phages modified with RGD, [56] TMV, [57,58] TMV modified with RGD, [59,60] TMV modified with phosphates, [61] and PVX modified with RGD, and MIPs. [17] In this work, the osteogenic differentiation of hMSCs was evaluated on PVX-E8-coated surfaces by Alizarin red staining and ALP assay, both of which showed a significant increase compared to the control ( Figure 3C, D).…”

Section: Vnp and Cell Interaction In Both 2d And 3d Culturesmentioning

confidence: 99%

Attachment of Ultralow Amount of Engineered Plant Viral Nanoparticles to Mesenchymal Stem Cells Enhances Osteogenesis and Mineralization

Lin

Schuphan

Dickmeis

et al. 2020

Adv Healthcare Materials

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Hydrogel-based materials are widely used to mimic the extracellular matrix in bone tissue engineering, although they often lack biofunctional cues. In the authors' previous work, Potato virus X (PVX), a flexible rod-shaped biocompatible plant virus nanoparticle (VNP) with 1270 coat protein subunits, is genetically modified to present functional peptides for generating a bone substitute. Here, PVX is engineered to present mineralization-and osteogenesis-associated peptides and laden in hydrogels at a concentration lower by two orders of magnitude. Its competence in mineralization is demonstrated both on 2D surfaces and in hydrogels and the superiority of enriched peptides on VNPs is verified and compared with free peptides and VNPs presenting fewer functional peptides. Alkaline phosphatase activity and Alizarin red staining of human mesenchymal stem cells increase 1.2-1.7 times when stimulate by VNPs. Engineered PVX adheres to cells, exhibiting a stimulation of biomimetic peptides in close proximity to the cells. The retention of VNPs in hydrogels is monitored and more than 80% of VNPs remain inside after several washing steps. The mechanical properties of VNP-laden hydrogels are investigated, including viscosity, gelling temperature, and compressive tangent modulus. This study demonstrates that recombinant PVX nanoparticles are excellent candidates for hydrogel nanocomposites in bone tissue engineering.

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Engineered Potato virus X nanoparticles support hydroxyapatite nucleation for improved bone tissue replacement

Cited by 26 publications

References 67 publications

Repurposing Plant Virus Nanoparticles

Repurposing Plant Virus Nanoparticles

<p>Tobacco Mosaic Viral Nanoparticle Inhibited Osteoclastogenesis Through Inhibiting mTOR/AKT Signaling</p>

Attachment of Ultralow Amount of Engineered Plant Viral Nanoparticles to Mesenchymal Stem Cells Enhances Osteogenesis and Mineralization

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