Xiao-Qiu Dou

Bioinspired Hierarchical Surface Structures with Tunable Wettability for Regulating Bacteria Adhesion

To circumvent the influence from varied topographies, the systematic study of wettability regulated Gram-positive bacteria adhesion is carried out on bioinspired hierarchical structures duplicated from rose petal structures. With the process of tuning the interfacial chemical composition of the self-assembled films from supramolecular gelators, the varied wettable surfaces from superhydrophilicity to superhydrophobicity can be obtained. The investigation of Gram-positive bacteria adhesion on the hierarchical surfaces reveals that Gram-positive bacteria adhesion is crucially mediated by peptidoglycan due to its different interaction mechanisms with wettable surfaces. The study makes it possible to systematically study the influence mechanism of wettability regulated bacteria adhesion and provides a sight to make the bioinspired topographies in order to investigate wettability regulated bioadhesion.

C2-symmetric benzene-based hydrogels with unique layered structures for controllable organic dye adsorption

With the development of industry, organic dyes used in printing, textile, plastic, foods, and cosmetics have brought health and environmental issues. A C2-symmetric benzene-based hydrogel with unique layered structure mimicking activated carbon was developed and found capable of the controllable adsorption of 97–99% of certain organic dyes (methylene blue and methyl violet 2B) within two minutes. The adsorption equilibrium of the dyes is in good agreement with the Langmuir adsorption isotherm model. The controllable adsorption of the dyes was confirmed by varying the pH of the medium. The hydrogels rapid, highly effective, reusable, and controllable adsorption of organic dyes makes it possible to not only adsorb toxic dyes from wastewater, but also be used as potential delivery vehicles for small drug molecules in the field of drug delivery.

Mechanical reinforcement of C2-phenyl-derived hydrogels for controlled cell adhesion

Many low molecular weight (LMWG) hydrogels have been widely used as scaffolds and substrates due to their particular structures and properties. However, LMWG hydrogels generally show a weak mechanical performance which confines their applications in the field of tissue engineering. Here, we report a new kind of hydrogel derived from the combination of a C2-phenyl-derived gelator and a polysaccharide (alginate). Rheology testing showed that the elastic modulus of C2-phenyl-derived hydrogels could be increased by nearly one order of magnitude by interpenetrating them with an alginate–calcium network. Increasing the concentrations of the gelator and calcium ions or decreasing the concentration of alginate will lead to an increase of the elastic modulus of the hybrid hydrogels. Imaging and spectroscopic analysis confirmed that the surface roughness and morphology of the hybrid hydrogels were almost the same with that of a pure C2 hydrogel. Significant improvements in cell adhesion and spreading were observed on the reinforced hydrogels. The new hybrid hydrogels have great potential for tissue engineering applications in vivo.

Gelator-polysaccharide hybrid hydrogel for selective and controllable dye release.

In this paper, 1,4-bi(phenylalanine-diglycol)-benzene (PDB) based Low-Molecular-Weight-Gelator (LMWG) hydrogels are modified using hydrophilic polysaccharide (sodium alginate). A set of techniques including Fourier transform infrared (FT-IR) spectroscopy, (1)H Nuclear Magnetic Resonance ((1)H NMR), X-ray powder diffraction (XRD), Ultraviolet-Visible (UV-Vis), and circular dichroism (CD) had confirmed a β-turn arrangement of PDB gelators and a semi-interpenetrating network (semi-IPN), which was formed through hydrogen bonds between LMWG fibers and polysaccharide chains. The evaluation of physicochemical properties of hydrogels indicates that gelator-polysaccharide hybrid hydrogels possess better mechanical and water retention properties than LMWG hydrogels. The release study of dyes (model drug) from both LMWG and hybrid hydrogels was carried out. Compared with PDB based hydrogels, hybrid hydrogels show a selective and controllable release property for certain dyes. The results suggest LMWG-polysaccharide hybrid gels may find potential applications as promising drug delivery vehicles for drug molecules.

Novel pH responsive hydrogels for controlled cell adhesion and triggered surface detachment

In the field of tissue engineering, the development of novel switchable cell growth scaffolds and triggered substrate surfaces is desirable for manipulating detachment of cells. In this paper, two kinds of pH-responsive C2-cyclohexane based cell scaffold biomaterials (G1 and G2) have been designed and synthesized. The highlight is that they can induce detachment of cells from materials surface by slightly reducing the pH of culture medium in an acceptable range. The abilities to culture cells on hydrogel scaffolds and guide cells to detach without proteolytic enzyme treatment are very useful for their development in various biomedical applications.

A Highly Efficient Self-Assembly of Responsive C2-Cyclohexane-Derived Gelators

The rational design and synthesis of a family of effective low-molecular-weight gelators (LMWGs) with a modular architecture based on a C(2) -1,4-diamide cyclohexane core are reported. Due to the high symmetry, the gelators are initially well distributed in solution and no trapped aggregates are formed before the assembly is triggered. The subsequent self-assembly process, which results in the formation of versatile gels, is highly efficient and can be triggered and tuned due to its remarkable dependence on the pH of solution. The assembly of different gelators is found to be closely related to the pK(a) of the corresponding functional substituents on the LMWGs. Primary cell culture experiments reveal that the hydrogels made under physiological conditions are promising as potential tailor-made microenvironments.

RGD anchored C2-benzene based PEG-like hydrogels as scaffolds for two and three dimensional cell cultures

Designing new types of cell scaffolds to resist protein adsorption and promote cell adhesion is becoming very important in the field of tissue engineering. Herein, by coupling ethylene glycol (EG) monomers and Arg-Gly-Asp (RGD) onto C2-benzene cores, a family of PEG-like low molecular weight gelators (LMWGs) functionalized with RGD is reported. Imaging and spectroscopic analysis by Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Circular Dichroism (CD) spectroscopy confirm that the functionalized LMWGs can self-assemble into nanofibrous hydrogels. The RGD functionalized nano-scaffolds were observed to overcome non-specific protein adsorption and promote adhesion of encapsulated cells through specific RGD-integrin binding. The PEG-like gelators may offer an effective model scaffold for cell cultures that generates specific cell-scaffold interactions with minimal non-specific protein adsorption and addresses some limitations of covalent polymeric scaffolds at the same time.

Wettability of supramolecular nanofibers for controlled cell adhesion and proliferation.

By employing smart self-assembly of 1,4-benyldicarbonxamide-phenylalanine (C2) derived supramolecular gelators, a simple way to construct nanofibrous environments with the controllable wettability is developed. The fast cell adhesion and proliferation on the least wettable fibers indicates an efficient control over cells, which is proved to be mainly mediated by the interaction between protein and the fibers. One typical merit superior to other materials is that cell adhesion can be regulated not only on two-dimensional (2D) substrates but also in three-dimensional (3D) microenvironments. This paves a novel way to deeply understand the influence of fiber wettability on cell behaviors in 3D environment.

Bioinspired Hierarchically Structured Surfaces for Efficient Capture and Release of Circulating Tumor Cells

The development of novel bioinspired surfaces with hierarchical micro- and nanoscale topographic structures for efficient capture and release of circulating tumor cells (CTCs) is reported. The capture of CTCs, facilitated by surface-immobilized epithelial cell adhesion molecule antibodies (anti-EpCAM), was shown to be significantly enhanced in novel three-dimensional hierarchically structured surfaces that were fabricated by replicating the natural micro- and nanostructures of rose petals. Under static conditions, these hierarchical capture substrates exhibited up to 6 times higher cell capture ability at concentrations of 100 cells mL-1 in contrast to flat anti-EpCAM-functionalized polydimethylsiloxane (PDMS) surfaces. As indicated by scanning electron microscopy (SEM) and immunofluorescent images, this enhancement can be in large part attributed to the topographical interaction between nanoscale cell surface components and nanostructures on the substrate. Similarly, the increased surface area affords a higher nominal coverage of anti-EpCAM, which increases the number of available binding sites for cell capture. By treating the substrates with the biocompatible reductant glutathione (GSH), up to 85% of the captured cells were released, which displayed over 98% cell viability after culturing on tissue culture polystyrene (TCP) for 24 h. Therefore, these bioinspired hierarchically structured and functionalized substrates can be successfully applied to capture CTCs, as well as release CTCs for subsequent analysis. These findings provide new prospects for designing cell-material interfaces for advanced cell-based biomedical studies in the future.

Isolated Reporter Bacteria in Supramolecular Hydrogel Microwell Arrays

The combination of supramolecular hydrogels formed by low molecular weight gelator self-assembly via noncovalent interactions within a scaffold derived from polyethylene glycol (PEG) affords an interesting approach to immobilize fully functional, isolated reporter bacteria in novel microwell arrays. The PEG-based scaffold serves as a stabilizing element and provides physical support for the self-assembly of the C2-phenyl-derived gelator on the micrometer scale. Supramolecular hydrogel microwell arrays with various shapes and sizes were used to isolate single or small numbers of Escherichia coli TOP10 pTetR-LasR-pLuxR-GFP. In the presence of the autoinducer N-(3-oxododecanoyl) homoserine lactone, the entrapped E. coli in the hydrogel microwell arrays showed an increased GFP expression. The shape and size of microwell arrays did not influence the fluorescence intensity and the projected size of the bacteria markedly, while the population density of seeded bacteria affected the number of bacteria expressing GFP per well. The hydrogel microwell arrays can be further used to investigate quorum sensing, reflecting communication in inter- and intraspecies bacterial communities for biology applications in the field of biosensors. In the future, these self-assembled hydrogel microwell arrays can also be used as a substrate to detect bacteria via secreted autoinducers.