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

Abstract

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.

Research progress on the biological modifications of implant materials in 3D printed intervertebral fusion cages

“…Developing a new generation of hydrogel-inorganic particle stem cell composite implant materials improves the physical and biological properties of engineered bone and cartilage tissue [ 76 ]. Genetically modified potato virus X (PVX) nanoparticles can produce bone-related functional peptides, which are ideal materials for preparing hydrogel nanocomposites in bone tissue engineering [ 77 ].…”

Bioconjugation Strategies for Tobacco Mild Green Mosaic Virus

“…In addition, viral nanotechnology is a powerful platform for specially controlled and programmed materials assembly for development of advanced biocatalytic materials [20–25] . Some prominent examples of plant viruses and bacteriophages utilized in viral nanotechnology include: virus‐like particles (VLPs, which are devoid of the viral genome) of Qβ and Physalis mottle virus (PhMV) [26,27] and VNPs from plants such as Cowpea mosaic virus (CPMV), Potato virus X (PVX), Turnip mosaic virus (TuMV) and Cowpea chlorotic mottle virus (CCMV) [28–35] . In particular, Tobacco mosaic virus (TMV) has been extensively analyzed for its reactivity and demonstrated as a robust platform in materials science, drug delivery, and structural biology [36–40] .…”

“…[20][21][22][23][24][25] Some prominent examples of plant viruses and bacteriophages utilized in viral nanotechnology include: viruslike particles (VLPs, which are devoid of the viral genome) of Qβ and Physalis mottle virus (PhMV) [26,27] and VNPs from plants such as Cowpea mosaic virus (CPMV), Potato virus X (PVX), Turnip mosaic virus (TuMV) and Cowpea chlorotic mottle virus (CCMV). [28][29][30][31][32][33][34][35] In particular, Tobacco mosaic virus (TMV) has been extensively analyzed for its reactivity and demonstrated as a robust platform in materials science, drug delivery, and structural biology. [36][37][38][39][40] Diverse applications have been made possible by the available chemical modification strategies.…”

A Topologically Engineered Gold Island for Programmed In Vivo Stem Cell Manipulation

“…[11][12][13][14] Multivalent display of RGD on tobacco mosaic virus could upregulate bone differentiation makers. [15][16][17] Kang et al reported a charged mobile nanoligand to regulate cellular adhesion and differentiation. [18] Our previous study has shown that photocontrolled presentation of nanoclustered RGD using an upconversion substrate can guide multidirectional differentiation of MSCs.…”

“…For instance, commercially available block copolymers comprising dispersed ligand clusters have been widely used to promote lineage‐specific differentiation of mesenchymal stem cells (MSCs) [11–14] . Multivalent display of RGD on tobacco mosaic virus could upregulate bone differentiation makers [15–17] . Kang et al.…”