Dopamine-Induced Surface Zwitterionization of Expanded Poly(tetrafluoroethylene) for Constructing Thermostable Bioinert Materials.

Although energy-demanding, the surface modification of polytetrafluoroethylene (PTFE) for biomedical applications is mandatory to mitigate irreversible biofouling that occurs whenever PTFE comes into contact with biological fluids. Here, we propose to take advantage of the adhesive properties of dopamine (DA) and of the antifouling ability of various zwitterionic monomers (sulfobetaine methacrylate (SBMA), sulfobetaine methacrylamide (SBAA), sulfobetaine acrylamide (SBAA'), and 4-vinylpyridine propylsulfobetaine (4VPPS)) and form antifouling coatings by copolymerization on the surface of expanded PTFE membranes. This simple, low-energy, and one-step coating procedure arises in significant biofouling mitigation. All zwitterionic coatings led to important reduction of biofouling by red blood cell conentrate (88-94%), platelet conentrate (70-90%), whole blood (40-66%), or bacteria (83-96%). Also, it is shown that the interactions of polydopamine with ePTFE are stable even at high temperatures. However, the zwitterionic monomers are differently affected. While the performance of SBMA coatings decreased (as SBMA is prone to hydrolysis), those of SBAA, SBAA', and 4VPPS coatings were generally maintained. All in all, this study illustrates that efficient and stable antifouling zwitterionic coatings can be generated onto PTFE membranes for biomedical applications, without the use of conventional high-energy-demanding surface modification processes.

Surface PEGylation via Ultrasonic Spray Deposition for the Biofouling Mitigation of Biomedical Interfaces.

Air plasma and spray technology are common methods for surface modification. In this study, air plasma is used to generate hydroxyl groups on various material surfaces. Then random copolymers of styrene and ethylene glycol methacrylate (PS-r-PEGMA) are spray-coated to achieve coating densities ranging between 0.1 and 0.6 mg/cm2. PS50-r-PEGMA50 led to the best overall antifouling properties, while a coating density of 0.3 mg/cm2 was enough to significantly reduce biofouling. This surface modification technique enabled efficient modification of a wide range of materials and biofouling reduction by at least 75% on polymeric surfaces (polystyrene, polyvinylidene fluoride, poly(tetrafluoroethylene), polydimethylsiloxane), metallic surfaces (steel, titanium alloy), or ceramic surface (glass). Applied to the modification of well plate used for blood-typing, this antifouling modification permitted to greatly increase the signal sensitivity (×4).

NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis.

Accelerated glycolysis is the main metabolic change observed in cancer, but the underlying molecular mechanisms and their role in cancer progression remain poorly understood. Here, we show that the deletion of the long noncoding RNA (lncRNA) Neat1 in MMTV-PyVT mice profoundly impairs tumor initiation, growth, and metastasis, specifically switching off the penultimate step of glycolysis. Mechanistically, NEAT1 directly binds and forms a scaffold bridge for the assembly of PGK1/PGAM1/ENO1 complexes and thereby promotes substrate channeling for high and efficient glycolysis. Notably, NEAT1 is upregulated in cancer patients and correlates with high levels of these complexes, and genetic and pharmacological blockade of penultimate glycolysis ablates NEAT1-dependent tumorigenesis. Finally, we demonstrate that Pinin mediates glucose-stimulated nuclear export of NEAT1, through which it exerts isoform-specific and paraspeckle-independent functions. These findings establish a direct role for NEAT1 in regulating tumor metabolism, provide new insights into the Warburg effect, and identify potential targets for therapy.

Influence of Photocatalysis on Blood Cell Attachment over Protein-Immobilized Polystyrene Surfaces Modified with a Poly(styrene)-b-Poly(acrylic acid) Copolymer.

In the present study, thrombocytes, erythrocytes, and leukocytes were individually brought into contact with different immobilized blood proteins on the surface of polystyrene (PS), which was modified with a poly(styrene)-b-poly(acrylic acid) copolymer. When the concentration of fibronectin was greater than 5 µg mL-1, the attachment of erythrocytes increased, which indicated that the modified PS surface was less compatible with erythrocytes. In addition, vitronectin and laminin attached on the surface increased the adhesion of thrombocytes; higher adhesion was observed for leukocytes in the cases of fibrinogen, lysozyme, and laminin. Interestingly, adhesion properties of blood cells on the protein surface could be influenced by the addition of metal oxide- and carbon-based photocatalysts. After a photocatalytic treatment by metal oxide-based TiO2, the adhesion amounts of erythrocytes improved slightly, whereas the adhesion of leukocytes and thrombocytes decreased after treatment with a carbon-based g-C3N4 nanosheet. Our results suggested that the surface modification of the substrate through photocatalysis using various photocatalysts along with the grafting of the poly(styrene)-b-poly(acrylic acid) copolymer could be a promising approach to alternatively control the blood compatibility on the protein surface.

The design of a thermoresponsive surface for the continuous culture of human pluripotent stem cells.

Commonly, stem cell culture is based on batch-type culture, which is laborious and expensive. We continuously cultured human pluripotent stem cells (hPSCs) on thermoresponsive dish surfaces, where hPSCs were partially detached on the same thermoresponsive dish by decreasing the temperature of the thermoresponsive dish to be below the lower critical solution temperature for only 30 min. Then, the remaining cells were continuously cultured in fresh culture medium, and the detached stem cells were harvested in the exchanged culture medium. hPSCs were continuously cultured for ten cycles on the thermoresponsive dish surface, which was prepared by coating the surface with poly(N-isopropylacrylamide-co-styrene) and oligovitronectin-grafted poly(acrylic acid-co-styrene) or recombinant vitronectin for hPSC binding sites to maintain hPSC pluripotency. After ten cycles of continuous culture on the thermoresponsive dish surface, the detached cells expressed pluripotency proteins and had the ability to differentiate into cells derived from the three germ layers in vitro and in vivo. Furthermore, the detached cells differentiated into specific cell lineages, such as cardiomyocytes, with high efficiency.

Superior Bioinert Capability of Zwitterionic Poly(4-vinylpyridine propylsulfobetaine) Withstanding Clinical Sterilization for Extended Medical Applications.

The field of bioinert materials is relatively mature, as unique molecular designs for antifouling have been regularly presented over the past 30 years. However, the effect of steam sterilization, a common procedure in hospitals for sterilizing biomedical devices in clinical uses, on the stability of antifouling and hemocompatible biomaterials remains unexplored. The only available set of data indicates that poly(sulfobetaine methacrylate) (SBMA) is unstable and loses its antifouling properties when exposed to hot humid air, depriving it of its attractiveness. Here, we present zwitterionic biomaterial gels of poly(4-vinylpyridine propylsulfobetaine) (4VPPS) and explore their propensity to biofouling before and after a 1 h steam sterilization at 121 °C. After incubation with erythrocytes, leukocytes, thrombocytes, whole blood, or various bacteria ( Escherichia coli, Stenotrophomonas maltophilia), the antifouling properties of unsterilized 4VPPS gels are comparable to those of SBMA gels. Importantly, they are maintained after steam sterilization, unlike those of SBMA gels, which shows that the structure of 4VPPS and the interactions with water remain unaffected by the humid heat treatment. The antifouling properties of gels coated on materials mimicking surfaces used in biomedical devices including stainless steel (surgical knife), silicon (biochips), or titanium (electrocautery pen) are also maintained after similar sterilization. In addition, repeated sterilizations do not affect the antifouling properties of 4VPPS. Therefore, these results provide a substantial advance over the current knowledge on antifouling materials for repeated usage in actual conditions that often involve, in a biomedical environment, steam sterilization.