Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD.

Tailoring metabolic activity assays for tumour-engineered 3D models.

Monitoring cell behaviour in hydrogel-based 3D models is critical for assessing their growth and response to cytotoxic treatment. Resazurin-based PrestoBlue and AlamarBlue reagents are frequently used metabolic activity assays when determining cell responses. However, both assays are largely applied to cell monolayer cultures but yet to have a defined protocol for use in hydrogel-based 3D models.

Interpenetrating Polymer Network Hydrogels with Tunable Viscoelasticity and Proteolytic Cleavability to Direct Stem Cells In Vitro.

The dynamic nature of cellular microenvironments, regulated by the viscoelasticity and enzymatic cleavage of the extracellular matrix, remains challenging to emulate in engineered synthetic biomaterials. To address this, a novel platform of cell-instructive hydrogels is introduced, composed of two concurrently forming interpenetrating polymer networks (IPNs). These IPNs consist of the same basic building blocks - four-armed poly(ethylene glycol) and the sulfated glycosaminoglycan (sGAG) heparin - are cross-linked through either chemical or physical interactions, allowing for precise and selective tuning of the hydrogel's stiffness, viscoelasticity, and proteolytic cleavability.

Microgels With Electrostatically Controlled Molecular Affinity to Direct Morphogenesis.

Concentration gradients of soluble signaling molecules-morphogens-determine the cellular organization in tissue development. Morphogen-releasing microgels have shown potential to recapitulate this principle in engineered tissue constructs, however, with limited control over the molecular cues in space and time. Inspired by the functionality of sulfated glycosaminoglycans (sGAGs) in morphogen signaling in vivo, a library of sGAG-based microgels is developed and designated as µGel Units to Instruct Development (µGUIDEs).

Development of a Screening Platform for Optimizing Chemical Nanosensor Materials.

Chemical sensors, relying on changes in the electrical conductance of a gas-sensitive material due to the surrounding gas, typically react with multiple target gases and the resulting response is not specific for a certain analyte species. The purpose of this study was the development of a multi-sensor platform for systematic screening of gas-sensitive nanomaterials. We have developed a specific Si-based platform chip, which integrates a total of 16 sensor structures.

Reshaping and enzymatic activity may allow viruses to move through the mucus.

Filamentous viruses like influenza and torovirus often display systematic bends and arcs of mysterious physical origin. We propose that such viruses undergo an instability from a cylindrically symmetric to a toroidally curved state. This "toro-elastic" state emerges spontaneous symmetry breaking under prestress due to short range spike protein interactions magnified by surface topography.

Y-switch: a spring-loaded synthetic gene switch for robust DNA/RNA signal amplification and detection.

Nucleic acid tests (NATs) are essential for biomedical diagnostics. Traditional NATs, often complex and expensive, have prompted the exploration of toehold-mediated strand displacement (TMSD) circuits as an economical alternative. However, the wide application of TMSD-based reactions is limited by 'leakage'-the spurious activation of the reaction leading to high background signals and false positives.

Mimicking foot protein: A versatile strategy for robust biomedical coatings.

Universal coatings with versatile surface adhesion, good mechanochemical robustness, and the capacity for secondary modification are of great scientific interest. However, incorporating these advantages into a system is still a great challenge. Here, we report a series of catechol-decorated polyallylamines (CPAs), denoted as pseudo- foot protein 5 (-Mefp-5), that mimic not only the catechol and amine groups but also the backbone of Mefp-5.

In Situ ATR-FTIR Studies on the β-Sheet Formation of Native and Regenerated Silk Material in Solution and Its Potential for Drug Releasing Coatings.

Dynamic attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy at both solutions and coatings of a semicrystalline silk material derived from was applied to monitor the β-sheet conformation, which is known to correlate with silk protein crystallinity. The secondary structure-sensitive Amide I band was analyzed. Two silk protein samples were studied: native-based silk buffer fibroin (NSF) was extracted from silk glands and regenerated silk fibroin (RSF) was extracted from degummed cocoons.

3D-Printed Hydrogels as Photothermal Actuators.

Thermoresponsive hydrogels were 3D-printed with embedded gold nanorods (GNRs), which enable shape change through photothermal heating. GNRs were functionalized with bovine serum albumin and mixed with a photosensitizer and poly(-isopropylacrylamide) (PNIPAAm) macromer, forming an ink for 3D printing by direct ink writing. A macromer-based approach was chosen to provide good microstructural homogeneity and optical transparency of the unloaded hydrogel in its swollen state.

A Multifunctional Nanostructured Hydrogel as a Platform for Deciphering Niche Interactions of Hematopoietic Stem and Progenitor Cells.

For over half a century, hematopoietic stem cells (HSCs) have been used for transplantation therapy to treat severe hematologic diseases. Successful outcomes depend on collecting sufficient donor HSCs as well as ensuring efficient engraftment. These processes are influenced by dynamic interactions of HSCs with the bone marrow niche, which can be revealed by artificial niche models.

Enhancing thromboresistance of neurovascular nickel-titanium devices with responsive heparin hydrogel coatings.

Background: Neurointerventional devices, particularly laser-cut thin-strut stents made of self-expanding nickel-titanium alloy, are increasingly utilized for endovascular applications in intracranial arteries and dural venous sinuses. Preventing thrombosis and stroke necessitates systemic anticoagulant and antiplatelet therapies with the risk of bleeding complications. Antithrombotic coatings present a promising solution.

Photocatalytic Zinc Oxide Nanoparticles in Antibacterial Ultrafiltration Membranes for Biofouling Control.

Global water scarcity is a threat that can be alleviated through membrane filtration technologies. However, the widespread adoption of membranes faces significant challenges, primarily due to membrane biofouling. This is the reason why membrane modifications have been under increasing investigation to address the fouling issues.

Precision Culture Scaling to Establish High-Throughput Vasculogenesis Models.

Hydrogel-based 3D cell cultures can recapitulate (patho)physiological phenomena ex vivo. However, due to their complex multifactorial regulation, adapting these tissue and disease models for high-throughput screening workflows remains challenging. In this study, a new precision culture scaling (PCS-X) methodology combines statistical techniques (design of experiment and multiple linear regression) with automated, parallelized experiments and analyses to customize hydrogel-based vasculogenesis cultures using human umbilical vein endothelial cells and retinal microvascular endothelial cells.

Optical deformations of azobenzene polymers: orientation approach other concepts.

It has been 30 years since the discovery of surface restructuring in thin azopolymer films by two independent research groups. A wide variety of topographical structures have been created by the application of two-/four-beam interference patterns, space light modulators and even helical beams. There are a number of comprehensive reviews which describe in detail the advances in superficial photopatterning of azopolymer films and macroscopic deformations of azonetworks.

Sweet Janus Particles: Multifunctional Inhibitors of Carbohydrate-Based Bacterial Adhesion.

and other bacteria use adhesion receptors, such as FimH, to attach to carbohydrates on the cell surface as the first step of colonization and infection. Efficient inhibitors that block these interactions for infection treatment are multivalent carbohydrate-functionalized scaffolds. However, these multivalent systems often lead to the formation of large clusters of bacteria, which may pose problems for clearing bacteria from the infected site.

Adsorbed polymer conjugates to adaptively inhibit blood coagulation activation by medical membranes.

Adaptive drug release can combat coagulation and inflammation activation at the blood-material interface with minimized side effects. For that purpose, poly(styrene-alt-maleic-anhydride) copolymers were conjugated to heparin via coagulation-responsive linker peptides and shown to tightly adsorb onto poly(ethersulfone) (PES)-surfaces from aqueous solutions as monolayers. Coagulation-responsive release of unfractionated as well as low molecular weight heparins from the respective coatings was demonstrated to be functionally beneficial in human plasma and whole blood incubation with faster release kinetics resulting in stronger anticoagulant effects.

Design, simulation and experimental analysis of a monolithic bending section for enhanced maneuverability of single use laparoscopic devices.

Standard laparoscopes, which are widely used in minimally invasive surgery, have significant handling limitations due to their rigid design. This paper presents an approach for a bending section for laparoscopes based on a standard semi-finished tube made of Nitinol with laser-cut flexure hinges. Flexure hinges simply created from a semi-finished product are a key element for realizing low-cost compliant structures with minimal design space.

On the Swelling of Polymer Network Strands.

Large scale computer simulations are employed to analyze the conformations of network strands in polymer networks at preparation conditions (characterized by a polymer volume fraction of ϕ) and when swollen to equilibrium (characterized by a polymer volume fraction ϕ < ϕ). Network strands in end-linked model networks are weakly stretched and partially swollen at preparation conditions as compared to linear polymers in the same solvent at ϕ. Equilibrium swelling causes non-ideal chain conformations characterized by an effective scaling exponent approaching 7/10 on intermediate length scales for increasing overlap of the chains.

Bioinspired Pyrano[2,3-]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation.

We have designed and synthesized a series of bioinspired pyrano[2,3-]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2,8-pyrano[2,3-]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction.

Bone marrow-derived mesenchymal stromal cells obstruct AML-targeting CD8 clonal effector and CAR T-cell function while promoting a senescence-associated phenotype.

Bone marrow mesenchymal stromal cells (MSCs) have been described as potent regulators of T-cell function, though whether they could impede the effectiveness of immunotherapy against acute myeloid leukemia (AML) is still under investigation. We examine whether they could interfere with the activity of leukemia-specific clonal cytotoxic T-lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells, as well as whether the immunomodulatory properties of MSCs could be associated with the induction of T-cell senescence. Co-cultures of leukemia-associated Wilm's tumor protein 1 (WT1) and tyrosine-protein kinase transmembrane receptor 1 (ROR1)-reactive CTLs and of CD123-redirected switchable CAR T cells were prepared in the presence of MSCs and assessed for cytotoxic potential, cytokine secretion, and expansion.