Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

Abstract

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.

Engineered Pullulan-Collagen-Gold Nano Composite Improves Mesenchymal Stem Cells Neural Differentiation and Inflammatory Regulation

“…AgNPs were verified to have an anti-bacterial ability. In vitro and in vivo measurements showed that FN–AgNPs significantly inhibited the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), promoted endothelialization for MSCs, and attenuated foreign body responses, demonstrating the potential vascular repair applications of FN–AgNPs [ 73 ]. Graphene oxide decorated with Au nanoparticles (Go–Au) was suggested to be a promising nanocarrier owing to its better biocompatibility and its ability to induce various differentiated cell types for MSCs such as neuron, endothelial cells, osteocytes, and adipocytes [ 74 ].…”

Current developments and future perspectives of nanotechnology in orthopedic implants: an updated review

“…The antimicrobial ability was increased with the formation of a hybrid structure of the collagen, BMP-2, and silver nanoparticles, and the cell adhesion and proliferation were increased by the surface roughness of the scaffold. A 48 h exposure of Wharton’s jelly-derived hMSCs to ∼30 μg/mL of AgNPs (5 nm) conjugated with fibronectin (FN-AgNPs) has been recently demonstrated to induce proliferation with the production of ROS in a low amount ( Hung et al, 2021 ). Significantly, FN-AgNPs also facilitated the migration of hMSCs and showed anti-inflammatory properties.…”

Dendrimer-Mediated Intracellular Delivery of Fibronectin Guides Macrophage Polarization to Alleviate Acute Lung Injury

“…Of particular interest, it has been found that FN-adsorbed hydrophilic titanium dioxide surface drives the macrophage polarization to anti-inflammatory M2 phenotype through the interaction of FN with macrophage integrins . There is also a finding suggesting that FN-functionalized Ag NPs suppress inflammation in monocytes and improve MSC differentiations, which may be a potential anti-inflammatory surface modification strategy . However, these studies are mainly focused on building material–FN biointerfaces, in which the studied mechanisms toward biomedical applications are mostly related to the FN signaling with cell-surface integrins, and the influence of an intracellular delivery of FN on a biological process, such as inflammation, has not been investigated.…”

“…13 There is also a finding suggesting that FN-functionalized Ag NPs suppress inflammation in monocytes and improve MSC differentiations, which may be a potential anti-inflammatory surface modification strategy. 14 However, these studies are mainly focused on building material−FN biointerfaces, in which the studied mechanisms toward biomedical applications are mostly related to the FN signaling with cell-surface integrins, and the influence of an intracellular delivery of FN on a biological process, such as inflammation, has not been investigated. It is a fact that, to present, safe and efficient delivery of protein into cells still remains a challenge.…”