Institute for Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany.
Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.
Adv Healthc Mater. 2024 Jun;13(16):e2304243. doi: 10.1002/adhm.202304243. Epub 2024 Mar 13.
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.
植物病毒纳米颗粒（VNPs）经基因工程改造后呈现出成骨线索，为骨组织工程中生物功能化水凝胶提供了一种很有前途的方法。柔性马铃薯 X 病毒（PVX）纳米颗粒通过以浓度依赖的方式呈现 RGD 基序、羟磷灰石结合肽（HABP）或连续多聚谷氨酸（E8），极大地增强了人骨髓间充质干细胞（hMSCs）的黏附和分化。因此，研究人员假设烟草花叶病毒纳米颗粒（Tobacco mosaic virus nanoparticles，TMV NPs）呈现出比 PVX 多 1.6 倍的功能肽，将改善这种影响。本研究假设在表面涂覆两种 VNPs 的组合上培养 hMSCs，这两种 VNPs 分别呈现用于细胞黏附和矿化的肽，可以对成骨产生额外的增强作用。对于这种组合，分化的 hMSCs 沉积的钙矿物质增加了两到三倍，而在涂覆有 PVX-RGD/PVX-HABP 的表面上生长的 hMSCs 的碱性磷酸酶活性显著超过其他任何 VNP 组合。通过使用具有不同功能的 VNPs 的组合，首次观察到了优异的附加效应。研究发现，灵活的 VNP 几何形状比功能肽的浓度起着更关键的作用。总之，各种呈现肽的植物 VNPs 表现出相加的增强效应，为有效地对骨组织工程中含细胞的水凝胶进行功能化提供了巨大的潜力。
