Macromolecular Bioscience

The synthesis of a set of novel, degradable, polymeric transfection vectors is described, based on copolymers of PEO, N,N-dimethylaminoethyl methacrylate and 2-methylene-1,3-dioxepane. All of the copolymers show only little cytotoxicity and efficient DNA complexation, and, in particular, the quaternized 57:43 poly(PEG-co-(MDO-co-DMAEMA)) copolymer is identified as optimal in cell transfection experiments.

Microwell chips (25 mm square) are manufactured and serve as a culture substrate-selecting platform for mesenchymal stem cells. Cells are grown in microwells coated with different biopolymers. Biopolymer substrates favoring cell differentiation can be selected based on the expression of N-cadherin, which is a cell-cell adhesion protein that may interact with the calcium on the polymer surface.

Acid-responsive electrospun fibers are fabricated by introducing sodium bicarbonate into PLLA fibers using an emulsion-based method. These novel electrospun fibrous scaffolds exhibit a rapid acid-responsive controlled drug release (early stage) and stable 3D structure as tissue engineering scaffolds (late stage) for cell growth.

Biomimetic macroporous matrices are synthesized using natural polymers like gelatin and alginate in order to provide selective cell attachment to the matrix by controlled exposure of a functional polymer surface in a composite matrix using different crosslinking chemistry.

A detailed cellular entry mechanism of conjugated polymer nanoparticles (CPNs) is presented. Cancer cells pretreated with an inhibitor of caveolae-mediated endocytosis (CvME) exhibit decreased CPN uptake. High co-localization with caveolin-1 proteins found in the caveolae and caveosomes further confirms CvME of CPNs. Non-toxicity and non-destructive delivery pathways support that CPNs are promising carriers, minimizing content degradation during delivery.

Generation of scaffold-free neo-cartilage on cryogel matrices is observed in vitro on specially designed cryogel matrices. Neo-cartilage is characterized for its similarity to the native cartilage by biochemical, histological and mechanical analysis. The results exhibit similarity between neo and native cartilage, so it can be a potential material to treat the lesions generated during osteoarthritis.

A folate-conjugated PEG coating on single walled carbon nanotubes is developed in a facile strategy that can target delivery of the anti-cancer drug, doxorubicin, into cancer cells and effectively induce cancer cell death, but shows negligible cytotoxicity to normal cells.

Successful delivery of small molecular drugs and therapeutic genes by Bcl-xL siRNA and doxorubicin (DOX) encapsulated polymersomes shows potential as a highly powerful nanocarrier-based dual therapy system for cancer treatment.

Amylose and polytetrahydrofuran (PTHF) can form inclusion complexes that are able to self-assemble to form supramolecules. Amylose, with its hydrophobic cavity, acts as host molecule and PTHF acts as guest molecule. The resulting complexes induce the formation of the so-called V-amylose, which is influenced by the arrangements of the guest PTHF chains inside or in between the amylose helices.

Osteogenic syringeable gels exploit the capability of osteoinductive poloxamine Tetronic 908 to form polypseudorotaxanes with αCD and to solubilize and sustainably release the simvastatin hydroxy acid form for synergic differentiation of mesenchymal stem cells to osteoblasts. αCD transforms dilute poloxamine/simvastatin dispersions into affordable osteogenic/osteoinductive networks that can be administered using minimally invasive techniques for local treatment of bone pathologies.

In order to develop small-diameter vascular grafts that have excellent hemocompatibility to prevent platelet adhesion and aggregation on the scaffold surface and simultaneously be suitable for vascular cell growth, a combined sulfated silk fibroin scaffold is fabricated by modifying a knitted silk scaffold with sulfated silk fibroin sponges. The scaffold may greatly improve the chances of successful vascular reconstruction.

A dual enzyme microgel is constructed based on the covalent crosslinking of Mn-THPP-(PEG₂₀₀₀-BA)₄ and seleno-ferritin (Se-Fn). The microgel exhibits excellent antioxidative activity in the protection of mitochondria against oxidative stress and lipid peroxidation due to the synergism of the Mn^III porphyrin (SOD mimic) and Se-Fn (GPx mimic).

Hemoglobin-conjugated micelles are prepared by the amidation reaction between hemoglobin and polymeric micelles fabricated from triblock copolymer with two different monomer sequences. Hemoglobin can be partially entrapped into the core of the micelles when the pH is adjusted to the isoelectric point of the hemoglobin.

The capability of a micropatterning platform in modulating cell shape to direct lineage commitment of human mesenchymal stem cells derived from different sources (i.e., bone marrow, fetal tissue, and adipose) is investigated. Myogenesis is shown to be the predominant differentiation activity at mRNA and protein levels in three types of micropatterned stem cells. The platform is thus demonstrated to be generic and could possibly be extended to any type of stem cell.

A patterned surface is fabricated based on controlled surface-initiated polymerization of monomer and degradation of the obtained polymer at the UV-exposed domains on the polymer surface with UV irradiation. Switching on and off of platelet adhesion on the polymer surface is realized with a precision down to single cell level. The dysfunctional platelets can be quantitatively detected based on the adhesive pattern.

Besides factors such as particle size, morphology, and surface charge, the hydrophilic/hydrophobic ratio of the micelle matrix also has a great effect on cellular uptake of micelles. The internalization of micelles with different hydrophilic/hydrophobic ratio into cells is through different endocytosis mechanisms.

The interaction of surfaces with biological species is largely controlled through the initial adsorption of proteins. Surface-attached hydrogel coatings can suppress protein adsorption and, subsequently, cell or blood platelet adhesion. The strong swelling of theses coatings excludes proteins either via size exclusion and/or via entropic shielding.

Hydrogels are highly hydrated polymers with structural properties similar to soft tissues. In view of bone regenerative applications, the incorporation of alkaline phosphatase (ALP) within hydrogels is a simple and promising strategy to generate scaffolds with both an organic and inorganic phase. Specifically, the enzymatic hydrolysis of organic phosphates, diffused from the physiological environment, leads to the formation of minerals.

Biocompatible polycaprolactone/poly(α,β)-DL-aspartic acid/collagen nanofibrous scaffolds are fabricated by electrospinning and nanohydroxyapatite (n-HA) is deposited by a calcium phosphate dipping method. These scaffolds are characterized for fiber morphology, hydrophilicity, porosity, and tensile properties. Mesenchymal stem cell (MSCs) cultures on these nanofibrous scaffolds to facilitate cell adhesion, proliferation, mineralization, and osteogenic differentiation.

Nanofibrous materials from poly(3-hydroxybutyrate), titanium dioxide nanoparticles, and COS are fabricated by an effective approach, consisting of electrospinning, electrospraying, and impregnation. The mats exhibit photocatalytic properties and a biocidal effect against pathogenic bacteria, and moreover, they provide a favorable environment for hMSCs.

The sequence composition is critical for DNA conformation and can impair its uses as a recognition mechanism in biosensing applications. Repeated sequence patterns such as polyT or PolyC, although similar, generate different sensor conformations when mixed with a polythiophene derivative DNA hybridization sensor. Knowledge of the impact of DNA sequences on biosensors can help improving biosensing systems.

The use of various gelatin gels containing alginate as a molecular delivery system is described. The concept, development and use of several protein-polysaccharide architectures to retain very small molecules and control their release is described. The strategy presented here resides in the use of enzymes to hydrolyze one of the two phases of the gel in a highly controlled way.