No abstract

Controlling the behavior of mesenchymal stem cells (MSCs) through topographic patterns is an effective approach for stem cell studies. We, herein, reported a facile method to create a dopamine (DA) pattern on poly(dimethylsiloxane) (PDMS). The topography of micropatterned DA was produced on PDMS after plasma treatment. The grid-topographic-patterned surface of PDMS-DA (PDMS-DA-P) was measured for adhesion force and Young's modulus by atomic force microscopy. The surface of PDMS-DA-P demonstrated less stiff and more elastic characteristics compared to either nonpatterned PDMS-DA or PDMS. The PDMS-DA-P evidently enhanced the differentiation of MSCs into various tissue cells, including nerve, vessel, bone, and fat. We further designed comprehensive experiments to investigate adhesion, proliferation, and differentiation of MSCs in response to PDMS-DA-P and showed that the DA-patterned surface had good biocompatibility and did not activate macrophages or platelets in vitro and had low foreign body reaction in vivo. Besides, it protected MSCs from apoptosis as well as excessive reactive oxygen species (ROS) generation. Particularly, the patterned surface enhanced the differentiation capacity of MSCs toward neural and endothelial cells. The stromal cell-derived factor-1α/CXantiCR4 pathway may be involved in mediating the self-recruitment and promoting the differentiation of MSCs. These findings support the potential application of PDMS-DA-P in either cell treatment or tissue repair.

In this study, polyethylene glycol (PEG) with hydroxyapatite (HA), with the incorporation of physical gold nanoparticles (AuNPs), was created and equipped through a surface coating technique in order to form PEG-HA-AuNP nanocomposites. The surface morphology and chemical composition were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), UV–Vis spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and contact angle assessment. The effects of PEG-HA-AuNP nanocomposites on the biocompatibility and biological activity of MC3T3-E1 osteoblast cells, endothelial cells (EC), macrophages (RAW 264.7), and human mesenchymal stem cells (MSCs), as well as the guiding of osteogenic differentiation, were estimated through the use of an in vitro assay. Moreover, the anti-inflammatory, biocompatibility, and endothelialization capacities were further assessed through in vivo evaluation. The PEG-HA-AuNP nanocomposites showed superior biological properties and biocompatibility capacity for cell behavior in both MC3T3-E1 cells and MSCs. These biological events surrounding the cells could be associated with the activation of adhesion, proliferation, migration, and differentiation processes on the PEG-HA-AuNP nanocomposites. Indeed, the induction of the osteogenic differentiation of MSCs by PEG-HA-AuNP nanocomposites and enhanced mineralization activity were also evidenced in this study. Moreover, from the in vivo assay, we further found that PEG-HA-AuNP nanocomposites not only facilitate the anti-immune response, as well as reducing CD86 expression, but also facilitate the endothelialization ability, as well as promoting CD31 expression, when implanted into rats subcutaneously for a period of 1 month. The current research illustrates the potential of PEG-HA-AuNP nanocomposites when used in combination with MSCs for the regeneration of bone tissue, with their nanotopography being employed as an applicable surface modification approach for the fabrication of biomaterials.

Gold nanoparticles (AuNPs) were fabricated with biocompatible collagen (Col) and then conjugated with berberine (BB), denoted as Au-Col-BB, to investigate the endocytic mechanisms in Her-2 breast cancer cell line and in bovine aortic endothelial cells (BAEC). Owing to the superior biocompatibility, tunable physicochemical properties, and potential functionalization with biomolecules, AuNPs have been well studied as carriers of biomolecules for diseases and cancer therapeutics. Composites of AuNPs with biopolymer, such as fibronectin or Col, have been revealed to increase cell proliferation, migration, and differentiation. BB is a natural compound with impressive health benefits, such as lowering blood sugar and reducing weight. In addition, BB can inhibit cell proliferation by modulating cell cycle progress and autophagy, and induce cell apoptosis in vivo and in vitro. In the current research, BB was conjugated on the Col-AuNP composite (“Au-Col”). The UV-Visible spectroscopy and infrared spectroscopy confirmed the conjugation of BB on Au-Col. The particle size of the Au-Col-BB conjugate was about 227 nm, determined by dynamic light scattering. Furthermore, Au-Col-BB was less cytotoxic to BAEC vs. Her-2 cell line in terms of MTT assay and cell cycle behavior. Au-Col-BB, compared to Au-Col, showed greater cell uptake capacity and potential cellular transportation by BAEC and Her-2 using the fluorescence-conjugated Au-Col-BB. In addition, the clathrin-mediated endocytosis and cell autophagy seemed to be the favorite endocytic mechanism for the internalization of Au-Col-BB by BAEC and Her-2. Au-Col-BB significantly inhibited cell migration in Her-2, but not in BAEC. Moreover, apoptotic cascade proteins, such as Bax and p21, were expressed in Her-2 after the treatment of Au-Col-BB. The tumor suppression was examined in a model of xenograft mice treated with Au-Col-BB nanovehicles. Results demonstrated that the tumor weight was remarkably reduced by the treatment of Au-Col-BB. Altogether, the promising findings of Au-Col-BB nanocarrier on Her-2 breast cancer cell line suggest that Au-Col-BB may be a good candidate of anticancer drug for the treatment of human breast cancer.

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.