Switchable and Obedient Interfacial Properties That Grant New Biomedical Applications.

Toward imitating the natural smartness and responsivity of biological systems, surface interfacial properties are considered to be responsive and tunable if they show a reactive behavior to an environmental stimulus. This is still quite different from many contemporary biomaterials that lack responsiveness to interact with blood and different body tissues in a physiological manner. Meanwhile it is possible to even go one step further from responsiveness to dual-mode switchability and explore "switchable" or "reversible" responses of synthetic materials. We understand "switchable biomaterials" as materials undergoing a stepwise, structural transformation coupled with considerable changes of interfacial and other surface properties as a response to a stimulus. Therewith, a survey on stimuli-induced dynamic changes of charge, wettability, stiffness, topography, porosity, and thickness/swelling is presented here, as potentially powerful new technologies especially for future biomaterial development. Since living cells constantly sense their environment through a variety of surface receptors and other mechanisms, these obedient interfacial properties were particularly discussed regarding their advantageous multifunctionality for protein adsorption and cell adhesion signaling, which may alter in time and with environmental conditions.

Cyclic Redox-Mediated Switching of Surface Properties of Thiolated Polysaccharide Multilayers and Its Effect on Fibroblast Adhesion.

Advanced technologies for controlled cell adhesion and detachment in novel biointerface designs profit from stimuli-responsive systems that are able to react to their environment. Here, a multilayer system made of thiolated chitosan and thiolated chondroitin sulfate was constructed, with the potential of switchable inter- and intramolecular thiol/disulfide interactions representing a redox-sensitive nanoplatform. Owing to the formation and cleavage of inherent disulfide bonds by oxidation and reduction, surface properties of the multilayer can be controlled toward protein adsorption/desorption and cell adhesion in a reversible manner. Oxidation of thiols by chloramine-T promotes fibronectin (FN) adsorption and fibroblast cell adhesion, whereas the reduction by tris(2-carboxyethyl)phosphine reverses these effects, leading to low FN adsorption and little cell adhesion and spreading. These effects on the biological systems are related to significant changes of wetting properties, zeta potential, and mechanical properties of these multilayer films. The system presented may be useful for biomedical applications as responsive and obedient surfaces in medical implants and support tissue regeneration.

Stimuli-Responsive Multilayers Based on Thiolated Polysaccharides That Affect Fibroblast Cell Adhesion.

Control of the biomaterial properties through stimuli-responsive polymeric platforms has become an essential technique in recent biomedical applications. A multilayer system of thiolated chitosan (t-Chi) and thiolated chondroitin sulfate (t-CS), consisting of five double layers ([t-Chi/t-CS]5), was fabricated here by applying a layer-by-layer coating strategy. To represent a novel class of chemically tunable nanostructures, the ability to cross-link pendant thiol groups was tested by a rise from pH 4 during layer formation to pH 9.3 and a more powerful chemical stimulus by using chloramine-T (ChT). Following both treatments, the resulting multilayers showed stimuli-dependent behavior, as demonstrated by their content of free thiols, wettability, surface charge, elastic modulus, roughness, topography, thickness, and binding of fibronectin. Studies with human dermal fibroblasts further demonstrated the favorable potential of the ChT-responsive multilayers as a cell-adhesive surface compared to pH-induced cross-linking. Because the [t-Chi/t-CS]5 multilayer system is responsive to stimuli such as the pH and redox environment, multilayer systems with disulfide bond formation may help to tailor their interaction with cells, film degradation, and controlled release of bioactive substances like growth factors in a stimuli-responsive manner useful in future wound healing and tissue engineering applications.

ZnO Q-dots as a potent therapeutic nanomedicine for in vitro cytotoxicity evaluation of mouth KB44, breast MCF7, colon HT29 and HeLa cancer cell lines, mouse ear swelling tests in vivo and its side effects using the animal model.

Nanoformulations derived from fine porous ZnO quantum dot nanoparticles (QD NPs) can offer strong potential medical applications; especially in cancer therapy. ZnO QD NPs was synthesized by sol-gel hydrothermal process, fast cold quenching and further smart surface functionalization methods to obtain ultrasmall size (1-4 nm) NPs. ZnO nanopolymer, a wetting agent, PEG co-solvent and water/oil emulsion stabilizer were considered in our nanofluid formulation. The resulting nanofluid was characterized by SEM, FTIR, photoluminescence, band gap energy, zeta potential and UV-Vis spectroscopy. The cytotoxic effects on the growth of four cancer cell lines were evaluated by MTT assay. The IC50 (µg/ml) values of 30, 41, 40 and 35 for KB44, MCF-7, HT29 and HeLa cells, respectively, after 48 h of nanoformulation treatment suggested the cytotoxic effect of this nanoformulation on these cell lines in a concentration-dependent manner (p < .05). ZnO nanofluid destroyed cancer cell lines more efficiently than the normal HFF-2 (IC50 = 105 µg/ml). The reduction in cell viability in response to ZnO nanofluid treatment induced apoptosis in the cultured cells. Skin sensitization test plus antibacterial activity were also measured. Side effect tests on 70 white mice in vivo resulted in only 3-4 abnormal situations in hepatic tissue section possibly due to the idiosyncratic drug reactions.

Synthesis of thiolated polysaccharides for formation of polyelectrolyte multilayers with improved cellular adhesion.

Intrinsic cross-linking is not only useful for increasing stability, but also for tailoring mechanical properties of polyelectrolyte multilayers (PEM) on implants and tissue engineering scaffolds. Here, a novel route for synthesizing thiolated chitosan (t-Chi) based on the application of 3,3'-dithiodipropionic acid was applied, while thiolated chondroitin sulfate (t-CS) was conjugated by 3,3'-dithiobis (propanoic hydrazide). Both products were subsequently reduced to obtain the free thiols. The thiol content, structural changes and degree of substitution were studied by UV-vis, FTIR, Raman and 1H NMR spectroscopy, respectively. Chi and CS can be used for PEM formation with the layer-by-layer method, due to the cationic nature of Chi at pH values below 5.0 and the anionic character of CS. Comparative studies on the formation of native Chi/CS versus t-Chi/t-CS PEM with surface plasmon resonance and ellipsometry revealed higher layer mass. We also found that the PEM composed of t-Chi/t-CS had superior cell adhesion properties for human keratinocytes in comparison to the native PEM.

A synthetic garden of state of the art natural protein nanoarchitectures dispersed in nanofluids.

As a significant discovery in the 20th century, carbon nanotubes are attracting particular attention in many unique fields such as electronics, catalysts, hydrogen storage composites, gas sensors, drug delivery, medical diagnostics, therapeutics and nanofluids. In this project, we focus on self-assembled synthetic special natural protein alpha-lactalbumin nanotubes with different (straight, waved, coiled, regularly bent, branched, beaded) shapes, nanospherical particles, nanorods, nanowires, nanopores, polyhedral (hexagonal network, spherical, cubic) nanostructures, nanochannels, nanofibers, nanosheets, nanoleaves, nanowave branched structures, nanobeads, nanoflowers, nanocapsules, novel nano-hybrids consisting of tubes and rods (new core-shell), nanocrystal shapes, apiary or cobweb, branched nanotubes with Y-junctions, nano membrane structures, nano sweep symmetrical shape, nano sponge structures, nano helical homogeneous structures and nano perpendicular and horizontal stable hollow single-walled natural protein nanotubes (NPNTs). These were successfully synthesized by the chemical hydrolysis sol--gel method and partial biochemical enzymatic hydrolysis by cleavage sites (Asp-X and Glu-X) of the milk protein a-lactalbumin by using various organic surfactants, pH controller functions and divalent metallic salt ions as a binding site or ions ligand formation between two bio-based building blocks to form remarkable various new morphologies in appearance of nanoemulsions and clear green nanofluids, for application in the diet nutrition food science and pharmaceutical industry. The characterization by SEM, TEM, XRD and Raman spectroscopy (specific D and G bond in protein nanotubes) confirmed the novelty of these products.