Manipulating Nanoparticle Aggregates Regulates Receptor-Ligand Binding in Macrophages.

The receptor-ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor magnetic nanoparticle aggregates of tunable sizes over the cell-adhesive RGD ligand (Arg-Gly-Asp)-active material surface while maintaining the density of dispersed ligands accessible to macrophages at constant. Lowering the accessible ligand dispersity by increasing the aggregate size at constant accessible ligand density facilitates the binding of integrin receptors to the accessible ligands, which promotes the adhesion of macrophages. In high ligand dispersity, distant magnetic manipulation to lift the aggregates (which increases ligand accessibility) stimulates the binding of integrin receptors to the accessible ligands available under the aggregates to augment macrophage adhesion-mediated pro-healing polarization both in vitro and in vivo. In low ligand dispersity, distant control to drop the aggregates (which decreases ligand accessibility) repels integrin receptors away from the aggregates, thereby suppressing integrin receptor-ligand binding and macrophage adhesion, which promotes inflammatory polarization. Here, we present "accessible ligand dispersity" as a novel fundamental parameter that regulates receptor-ligand binding, which can be reversibly manipulated by increasing and decreasing the ligand accessibility. Limitless tuning of nanoparticle aggregate dimensions and morphology can offer further insight into the regulation of receptor-ligand binding in host cells.

Nano-graphene oxide/polyurethane nanofibers: mechanically flexible and myogenic stimulating matrix for skeletal tissue engineering.

For skeletal muscle engineering, scaffolds that can stimulate myogenic differentiation of cells while possessing suitable mechanical properties (e.g. flexibility) are required. In particular, the elastic property of scaffolds is of importance which helps to resist and support the dynamic conditions of muscle tissue environment. Here, we developed highly flexible nanocomposite nanofibrous scaffolds made of polycarbonate diol and isosorbide-based polyurethane and hydrophilic nano-graphene oxide added at concentrations up to 8%. The nano-graphene oxide incorporation increased the hydrophilicity, elasticity, and stress relaxation capacity of the polyurethane-derived nanofibrous scaffolds. When cultured with C2C12 cells, the polyurethane-nano-graphene oxide nanofibers enhanced the initial adhesion and spreading of cells and further the proliferation. Furthermore, the polyurethane-nano-graphene oxide scaffolds significantly up-regulated the myogenic mRNA levels and myosin heavy chain expression. Of note, the cells on the flexible polyurethane-nano-graphene oxide nanofibrous scaffolds could be mechanically stretched to experience dynamic tensional force. Under the dynamic force condition, the cells expressed significantly higher myogenic differentiation markers at both gene and protein levels and exhibited more aligned myotubular formation. The currently developed polyurethane-nano-graphene oxide nanofibrous scaffolds, due to their nanofibrous morphology and high mechanical flexibility, along with the stimulating capacity for myogenic differentiation, are considered to be a potential matrix for future skeletal muscle engineering.

Nano-graphene oxide incorporated into PMMA resin to prevent microbial adhesion.

OBJECTIVE: Although polymethyl methacrylate (PMMA) is widely used as a dental material, a major challenge of using this substance is its poor antimicrobial (anti-adhesion) effects, which increase oral infections. Here, graphene-oxide nanosheets (nGO) were incorporated into PMMA to introduce sustained antimicrobial-adhesive effects by increasing the hydrophilicity of PMMA. METHODS: After characterizing nGO and nGO-incorporated PMMA (up to 2wt%) in terms of morphology and surface characteristics, 3-point flexural strength and hardness were evaluated. The anti-adhesive effects were determined for 4 different microbial species with experimental specimens and the underlying anti-adhesive mechanism was investigated by a non-thermal oxygen plasma treatment. Sustained antimicrobial-adhesive effects were characterized with incubation in artificial saliva for up to 28 days. RESULTS: The typical nanosheet morphology was observed for nGO. Incorporating nGO into PMMA roughened its surface and increased its hydrophilicity without compromising flexural strength or surface hardness. An anti-adhesive effect after 1h of exposure to microbial species in artificial saliva was observed in nGO-incorporated specimens, which accelerated with increasing levels of nGO without significant cytotoxicity to oral keratinocytes. Plasma treatment of native PMMA demonstrated that the antimicrobial-adhesive effects of nGO incorporation were at least partially due to increased hydrophilicity, not changes in the surface roughness. A sustained antimicrobial-adhesive property against Candida albicans was observed in 2% nGO for up to 28 days. SIGNIFICANCE: The presence of sustained anti-adhesion properties in nGO-incorporated PMMA without loading any antimicrobial drugs suggests the potential usefulness of this compound as a promising antimicrobial dental material for dentures, orthodontic devices and provisional restorative materials.

Preparation of Self-Activated Fluorescence Mesoporous Silica Hollow Nanoellipsoids for Theranostics.

The newly developed multifunctional (self-activated fluorescent, mesoporous, and biocompatible) hollow mesoporous silica nanoellipsoids (f-hMS) are potentially useful as a delivery system of drugs for therapeutics and imaging purposes. For the synthesis of f-hMS, self-activated fluorescence hydroxyapatite (fHA) was used as a core template. A mesoporous silica shell was obtained by silica formation and subsequent removal of the fHA core, which resulted in a hollow-cored f-hMS. Although the silica shell provided a highly mesoporous structure, enabling an effective loading of drug molecules, the fluorescent property of fHA was also well-preserved in the f-hMS. Cytochrome c and doxorubicin, used as a model protein and anticancer drug, respectively, were shown to be effectively loaded onto f-hMS and were then released in a sustainable and controllable manner. The f-hMS was effectively taken up by the cells and exhibited fluorescent labeling while preserving excellent cell viability. Overall, the f-hMS nanoreservoir may be useful as a multifunctional carrier system for drug delivery and cell imaging.