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.
Highlights
Various biomolecules used for the surface modification of biomaterials have been certified to ameliorate biocompatibility, cell proliferation, and to stimulate differentiation [1,2]
The surface morphology of AgNP was observed by scanning electron microscope (SEM) analysis (Figure 1A)
The results showed the expression in FN-AgNP 30.2 ppm group
Summary
Various biomolecules used for the surface modification of biomaterials have been certified to ameliorate biocompatibility, cell proliferation, and to stimulate differentiation [1,2]. Synthetic vascular grafts often fail because of at the implantation site and poor endothelialization capacity [4]. In order to conquer these barriers, functional endothelial cell (EC) seeding on vascular grafts was created [5]. Since the source of ECs is limited, appropriate biological performance and superior biocompatibility of synthetic grafts as well as high endothelialization capacity to reduce immune response after implantation is crucial to ensure the success of a long-term implant. Previous research has indicated that fibronectin is distributed in connective tissue and contributes to angiogenesis and vascular remodeling [9,10]. Other literature elucidates that the interaction between cells, growth factors, and FN can modulate appropriate microenvironment in tissue regeneration [11]
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