Abstract
A nanocomposite composed of polyethylene glycol (PEG) incorporated with various concentrations (~17.4, ~43.5, ~174 ppm) of gold nanoparticles (Au) was created to investigate its biocompatibility and biological performance in vitro and in vivo. First, surface topography and chemical composition was determined through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), free radical scavenging ability, and water contact angle measurement. Additionally, the diameters of the PEG-Au nanocomposites were also evaluated through dynamic light scattering (DLS) assay. According to the results, PEG containing 43.5 ppm of Au demonstrated superior biocompatibility and biological properties for mesenchymal stem cells (MSCs), as well as superior osteogenic differentiation, adipocyte differentiation, and, particularly, neuronal differentiation. Indeed, PEG-Au 43.5 ppm induced better cell adhesion, proliferation and migration in MSCs. The higher expression of the SDF-1α/CXCR4 axis may be associated with MMPs activation and may have also promoted the differentiation capacity of MSCs. Moreover, it also prevented MSCs from apoptosis and inhibited macrophage and platelet activation, as well as reactive oxygen species (ROS) generation. Furthermore, the anti-inflammatory, biocompatibility, and endothelialization capacity of PEG-Au was measured in a rat model. After implanting the nanocomposites into rats subcutaneously for 4 weeks, PEG-Au 43.5 ppm was able to enhance the anti-immune response through inhibiting CD86 expression (M1 polarization), while also reducing leukocyte infiltration (CD45). Moreover, PEG-Au 43.5 ppm facilitated CD31 expression and anti-fibrosis ability. Above all, the PEG-Au nanocomposite was evidenced to strengthen the differentiation of MSCs into various cells, including fat, vessel, and bone tissue and, particularly, nerve cells. This research has elucidated that PEG combined with the appropriate amount of Au nanoparticles could become a potential biomaterial able to cooperate with MSCs for tissue regeneration engineering.
Highlights
Traumatic nerve injuries contribute to a high proportion of clinical symptoms and commonly cause the loss of motor/sensory functions, degeneration of nerve fibers, and even the death of neurons [1,2]
The Fourier-transform infrared spectroscopy (FTIR) spectra indicated that the specific peaks of pure polyethylene glycol (PEG) were 2931 cm−1 (-CH2 vibration), 2868 cm−1 (-CH3) and 1105 cm−1 (OH vibration), and these peaks were found in PEG-Au 17.4, PEG-Au 43.5, and PEG-Au 174 ppm groups
As demonstrated through in vitro assays, since PEG-Au exhibited advanced biocompatibility and biological performance for mesenchymal stem cells (MSCs), in the concentration of 43.5 ppm, it could superiorly enhance cell survival, migration and differentiation abilities when involved with the expression of CXCR4/SDF-1α and matrix metalloproteinase (MMP-2/9) activation
Summary
Traumatic nerve injuries contribute to a high proportion of clinical symptoms and commonly cause the loss of motor/sensory functions, degeneration of nerve fibers, and even the death of neurons [1,2]. A previous study had verified that neural stem cells (NSCs) could well restore neuronal functions due to their self-renewal and multipotential properties [4]. In spite of their advanced abilities, NSCs still require extra bioactive molecules to maintain cell survival and promote differentiation ability while taking on the risk of developing into a tumor after being implanted at the area of injury [5]. Polyethylene glycol (PEG) was shown to be both highly hydrophilic and biocompatible regarding the synthesis of hydrogels in drug delivery and tissue regeneration treatment. A study revealed that combining cellulose acetate butyrate (CAB) nanofibers with hydrophilic polyethylene glycol (PEG) could improve the properties of CAB. The above findings support PEG as being a potential biomaterial for tissue engineering through its ability to improve the properties of nanocomposites
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