The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.

Background and Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, dense LDLs.

Teleproctoring for Training in Structural Heart Interventions: Initial Real-World Experience During the COVID-19 Pandemic.

Background Proctoring represents a cornerstone in the acquisition of state-of-the-art cardiovascular interventions. Yet, travel restrictions and containment measures during the COVID-19 pandemic limited on-site proctoring for training and expert support in interventional cardiology. Methods and Results We established a teleproctoring setup for training in a novel patent foramen ovale closure device system (NobleStitch EL, HeartStitch Inc, Fountain Valley, CA) at our institution using web-based real-time bidirectional audiovisual communication.

Preclinical assessment of a modified Occlutech left atrial appendage closure device in a porcine model.

Left atrial appendage (LAA) closure is being developed as an alternative for stroke prevention in patients with atrial fibrillation that cannot tolerate long-term oral anticoagulation. To assess the feasibility, safety, and performance of a novel modified Occlutech LAA closure device in a preclinical porcine model, the modified Occlutech modified Occlutech Plus LAA closure device was implanted in 12 female pigs (25-39 kg body weight) under fluoroscopic and transesophageal echocardiography (TEE) guidance. Procedural and technical success, as well as safety of LAA closure, were evaluated peri-procedurally and after 4, 8, and 12 weeks.

The influence of different rewetting procedures on the thrombogenicity of nanoporous poly(ether imide) microparticles.

Nanoporous microparticles prepared from poly(ether imide) (PEI) are discussed as candidate adsorber materials for the removal of uremic toxins during apheresis. Polymers exhibiting such porosity can induce the formation of micro-gas/air pockets when exposed to fluids. Such air presenting material surfaces are reported to induce platelet activation and thrombus formation.

Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels.

Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the "Hen's egg test on chorioallantoic membrane" (HET-CAM) test and a mouse model.

Comparative analysis of adeno-associated virus serotypes for gene transfer in organotypic heart slices.

Background: Vectors derived from adeno-associated viruses (AAVs) are widely used for gene transfer both in vitro and in vivo and have gained increasing interest as shuttle systems to deliver therapeutic genes to the heart. However, there is little information on their tissue penetration and cytotoxicity, as well as the optimal AAV serotype for transferring genes to diseased hearts. Therefore, we aimed to establish an organotypic heart slice culture system for mouse left ventricular (LV) myocardium and use this platform to analyze gene transfer efficiency, cell tropism, and toxicity of different AAV serotypes.

Formulation of drug-loaded oligodepsipeptide particles with submicron size.

The size of particulate carriers is key to their transport and distribution in biological systems, and needs to be tailored in the higher submicron range to enable follicular uptake for dermal treatment. Oligodepsipeptides are promising nanoparticulate carrier systems as they can be designed to exhibit enhanced interaction with drug molecules. Here, a fabrication scheme for drug-loaded submicron particles from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diol (OBMD) is presented based on an emulsion solvent evaporation method with cosolvent, surfactant, and polymer concentration as variable process parameters.

Strategies for simultaneous and successive delivery of RNA.

Advanced non-viral gene delivery experiments often require co-delivery of multiple nucleic acids. Therefore, the availability of reliable and robust co-transfection methods and defined selection criteria for their use in, e.g.

Spheroid formation of human keratinocyte: Balancing between cell-substrate and cell-cell interaction.

Background: The formation of spheroids is tightly regulated by intrinsic cell-cell and cell-substrate interactions.

Objective: The chitosan (CS)-coating was applied to investigate the driven force directed the spheroid formation.

Methods: The effects of CS on cell functions were studied.

Functional requirements for polymeric implant materials in head and neck surgery.

Background: The pharyngeal reconstruction is a challenging aspect after pharyngeal tumor resection. The pharyngeal passage has to be restored to enable oral alimentation and speech rehabilitation. Several techniques like local transposition of skin, mucosa and/or muscle, regional flaps and free vascularized flaps have been developed to reconstruct pharyngeal defects following surgery, in order to restore function and aesthetics.

Intracardiac echocardiography to enable successful edge-to-edge transcatheter tricuspid valve repair in patients with insufficient TEE quality.

Background: Transesophageal echocardiography (TEE) as a guiding tool for edge-to-edge transcatheter tricuspid valve repair (EETVr) using MitraClip (Abbott Vascular, Santa Clara, USA) may not offer sufficient image quality in a significant proportion of patients.

Objectives: Intracardiac echocardiography (ICE) as additional guiding tool in EETVr with the MitraClip device.

Methods: Appropriate angulations of the ICE catheter to visualize each commissure of the tricuspid valve were established in 3D printed heart models.

The effects of oscillatory temperature on HaCaT keratinocyte behaviors.

Background: Keratinocytes are exposed to a thermal gradient throughout epidermal layers in human skin depending on environmental temperatures.

Objective: Here, the effect of cyclic temperature changes (ΔT) on HaCaT cell behaviors was explored.

Methods: HaCaT cells were cultured at constant temperature (37 °C or 25 °C) or under ΔT conditions.

Supramolecular Gelatin Networks Based on Inclusion Complexes.

Hydrogel forming physical networks based on gelatin are an attractive approach toward multifunctional biomaterials with the option of reshaping, self-healing, and stimuli-sensitivity. However, it is challenging to design such gelatin-based hydrogels to be stable at body temperature. Here, gelatin functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) side chains is crosslinked with cyclodextrin (CD) dimers under formation of inclusions complexes.

The impact of moderate Aortic Valve Disease in patients undergoing MitraClip for severe MR.

Background: High surgical risk patients presenting with severe mitral valve regurgitation (MR) and concomitant aortic valve disease are frequently a challenge for the interdisciplinary heart team meeting. If open-heart surgery for severe MR is performed, aortic stenosis (AS) or regurgitation (AR) is corrected during the same procedure if at least moderate severity of AS or AR has been confirmed. In patients with prohibitive surgical risk, optimal management strategies in the light of available transcatheter interventions still needs to be established.

Concepts for efficient preparation of particulate polymer carrier systems by droplet-based microfluidics.

Droplet-based microfluidics has grown out of its infancy as technical solutions became available for a broad community of researchers aiming at highly defined structures of polymer-based drug carrier systems. While the beauty of obtained particles and the precision of their (continuous) production may be very fascinating from a scientific perspective, microfluidics is further developing towards the use in production processes. This review summarizes recent concepts and developments in droplet-based microfluidics covering theoretical aspects of the operation principle as well as approaches to increased throughput and thus to enable efficient production.

Salt-Induced Shape-Memory Effect in Gelatin-Based Hydrogels.

Hydrophilic biopolymers display a strong tendency for self-organization into stable secondary, tertiary, and quaternary structures in aqueous environments. These structures are sensitive to changes in external conditions, such as temperature, pH or ions/salts, which may lead to molecular and/or macroscopic transitions. Here, we report on biopolymer-based stimuli-sensitive switchable matrices showing a shape-memory function as an output being alternatively switched by two different input signals, such as environmental changes in salt concentration or temperature.

mRNA Transfection-Induced Activation of Primary Human Monocytes and Macrophages: Dependence on Carrier System and Nucleotide Modification.

Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes.

A novel selection strategy for antibody producing hybridoma cells based on a new transgenic fusion cell line.

The use of monoclonal antibodies is ubiquitous in science and biomedicine but the generation and validation process of antibodies is nevertheless complicated and time-consuming. To address these issues we developed a novel selective technology based on an artificial cell surface construct by which secreted antibodies were connected to the corresponding hybridoma cell when they possess the desired antigen-specificity. Further the system enables the selection of desired isotypes and the screening for potential cross-reactivities in the same context.

Aptamer supported in vitro endothelialization of poly(ether imide) films.

Implantation of synthetic small-diameter vascular bypass grafts is often associated with an increased risk of failure, due to thrombotic events or late intimal hyperplasia. As one of the causes an insufficient hemocompatibility of the artificial surface is discussed. Endothelialization of synthetic grafts is reported to be a promising strategy for creating a self-renewing and regulative anti-thrombotic graft surface.

Polymeric sheet actuators with programmable bioinstructivity.

Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSCs).

In vivo biocompatibility study of degradable homo- versus multiblock copolymers and their (micro)structure compared to an established biomaterial.

Copolyetheresterurethane (PDC) is a biodegradable, shape-memory biomaterial, which has been shown to be of low toxicity and pro-angiogenic in vitro. In the present study we examined the in vivo compatibility of PDC as a compression molded film and as electrospun scaffolds and its well established constituent, the homopolymer poly(p-dioxanone) (PPDO), which were compared with the clinically used poly[(vinylidene fluoride)-co-hexafluoropropene] (PVDF) as reference material. The materials were implanted in the subcutaneous tissue of mice and the host responses were analyzed histologically 7 and 28 days after implantation.

Substrate-enzyme affinity-based surface modification strategy for endothelial cell-specific binding under shear stress.

Establishing an endothelial cell (EC) monolayer on top of the blood contacting surface of grafts is considered to be a promising approach for creating a hemocompatible surface. Here we utilized the high affinity interactions between the EC plasma membrane expressed enzyme called endothelin converting enzyme-1 (ECE-1) and its corresponding substrate big Endothelin-1 (bigET-1) to engineer an EC-specific binding surface. Since enzymatic cleavage of substrates require physical interaction between the enzyme and its corresponding substrate, it was hypothesized that a surface with chemically immobilized synthetic bigET-1 will preferentially attract ECs over other types of cells found in vascular system such as vascular smooth muscle cells (VSMCs).

Fundamental insights in PLGA degradation from thin film studies.

Poly(lactide-co-glycolide)s are commercially available degradable implant materials, which are typically selected based on specifications given by the manufacturer, one of which is their molecular weight. Here, we address the question whether variations in the chain length and their distribution affect the degradation behavior of Poly[(rac-lactide)-co-glycolide]s (PDLLGA). The hydrolysis was studied in ultrathin films at the air-water interface in order to rule out any morphological effects.