Electrically Controlled Click-Chemistry for Assembly of Bioactive Hydrogels on Diverse Micro- and Flexible Electrodes.

The seamless integration of electronics with living matter requires advanced materials with programmable biological and engineering properties. Here electrochemical methods to assemble semi-synthetic hydrogels directly on electronically conductive surfaces are explored. Hydrogels consisting of poly (ethylene glycol) (PEG) and heparin building blocks are polymerized by spatially controlling the click reaction between their thiol and maleimide moieties.

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.

Rapid prototyping of soft bioelectronic implants for use as neuromuscular interfaces.

Neuromuscular interfaces are required to translate bioelectronic technologies for application in clinical medicine. Here, by leveraging the robotically controlled ink-jet deposition of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ activation of electrode surfaces via cold-air plasma, we show that soft biocompatible materials can be rapidly printed for the on-demand prototyping of customized electrode arrays well adjusted to specific anatomical environments, functions and experimental models. We also show, with the monitoring and activation of neuronal pathways in the brain, spinal cord and neuromuscular system of cats, rats and zebrafish, that the printed bioelectronic interfaces allow for long-term integration and functional stability.

Designed Ankyrin Repeat Protein (DARPin) to target chimeric antigen receptor (CAR)-redirected T cells towards CD4 T cells to reduce the latent HIV cell reservoir.

Chimeric Antigen Receptor (CAR)-redirected T cells show great efficacy in the patient-specific therapy of hematologic malignancies. Here, we demonstrate that a DARPin with specificity for CD4 specifically redirects and triggers the activation of CAR engineered T cells resulting in the depletion of CD4 target cells aiming for elimination of the human immunodeficiency virus (HIV) reservoir.

Generation of three induced pluripotent cell lines (iPSCs) from an Aicardi-Goutières syndrome (AGS) patient harboring a deletion in the genomic locus of the sterile alpha motif and HD domain containing protein 1 (SAMHD1).

Aicardi-Goutières syndrome (AGS) is a hereditary early onset encephalopathy. AGS patients display variable clinical manifestations including intracranial calcification, cerebral atrophy, white matter abnormalities and characteristic leukocytosis as well as a constitutive upregulation of type I IFN production indicative of a type I interferonopathy. Seven genes (SAMHD1, TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, IFIH1) have been associated with the AGS phenotype, up to now.

Induced pluripotent stem cell line (PEIi003-A) derived from an apparently healthy male individual.

Induced pluripotent stem cells (iPSCs) are a useful tool to investigate pathomechanistic and cellular processes due to their differentiation potential into different somatic cell types in vitro. Here, we have generated iPSCs from an apparently healthy male individual using an integration-free reprogramming method. The resulting iPSCs are pluripotent and display a normal karyotype.

Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials.

Tissue transglutaminase (TGase 2) is proposed to be important for biomaterial-tissue interactions due to its presence and versatile functions in the extracellular environment. TGase 2 catalyzes the cross-linking of proteins through its Ca-dependent acyltransferase activity. Moreover, it enhances the interactions between fibronectin and integrins, which in turn mediates the adhesion, migration, and motility of the cells.

Induced pluripotent stem cells (iPSCs) derived from a renpenning syndrome patient with c.459_462delAGAG mutation in PQBP1 (PEIi001-A).

The Renpenning syndrome spectrum is a rare X-linked mental retardation syndrome characterized by intellectual disability, microcephaly, low stature, lean body and hypogonadism. Mutations in the polyglutamine tract binding protein 1 (PQBP1) locus are causative for disease. Here, we describe the generation of an iPSC line from a patient mutated in the polar amino acid-rich domain of PQBP1 resulting in a C-terminal truncated protein (c.

Highly Conductive, Stretchable, and Cell-Adhesive Hydrogel by Nanoclay Doping.

Electrically conductive materials that mimic physical and biological properties of tissues are urgently required for seamless brain-machine interfaces. Here, a multinetwork hydrogel combining electrical conductivity of 26 S m , stretchability of 800%, and tissue-like elastic modulus of 15 kPa with mimicry of the extracellular matrix is reported. Engineering this unique set of properties is enabled by a novel in-scaffold polymerization approach.

Dephosphorylation of the HIV-1 restriction factor SAMHD1 is mediated by PP2A-B55α holoenzymes during mitotic exit.

SAMHD1 is a critical restriction factor for HIV-1 in non-cycling cells and its antiviral activity is regulated by T592 phosphorylation. Here, we show that SAMHD1 dephosphorylation at T592 is controlled during the cell cycle, occurring during M/G transition in proliferating cells. Using several complementary proteomics and biochemical approaches, we identify the phosphatase PP2A-B55α responsible for rendering SAMHD1 antivirally active.

Insights into binding of S100 proteins to scavenger receptors: class B scavenger receptor CD36 binds S100A12 with high affinity.

The EF-hand type calcium-binding protein S100A12 exerts numerous intra- and extracellular functions of (patho)physiological relevance. Therefore, receptors of S100A12 are of high interest for research and clinical applications. Beside the extensively studied receptor for advanced glycation endproducts (RAGE), G-protein coupled receptors and more recently, scavenger receptors are suggested to be putative S100A12 receptors.

Gelatin-based Hydrogel Degradation and Tissue Interaction : Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice.

Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation).

A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.

Unlabelled: In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS-CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available.

Optical imaging of COX-2: studies on an autofluorescent 2,3-diaryl-substituted indole-based cyclooxygenase-2 inhibitor.

This study aimed at in vivo visualization of cyclooxygenase-2 (COX-2) by optical imaging using a representative compound of a class of autofluorescent 2,3-diaryl-substituted indole-based selective COX-2 inhibitors (2,3-diaryl-indole coxibs). COX-2 was successfully visualized in mice models with phorbol myristate ester (TPA)-induced inflammation or bearing xenografted human melanoma cells by 2-[4-(aminosulfonyl)phenyl]-3-(4-methoxyphenyl)-1H-indole (C1). COX-2 protein expression in both TPA-induced inflammatory sites and human melanoma xenografts was confirmed by immunoblotting.

Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties.

Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration.

Visualization of cyclooxygenase-2 using a 2,3-diarylsubstituted indole-based inhibitor and confocal laser induced cryofluorescence microscopy at 20K in melanoma cells in vitro.

This study aimed at visualization of cyclooxygenase-2 (COX-2) protein expression in melanoma cells by confocal laser induced cryofluorescence microscopy using 4-(3-(4-methoxyphenyl)-1H-indol-2-yl)benzene-sulfonamide (C1) representative for a novel class of autofluorescent 2,3-diarylsubstituted indole-based selective COX-2 inhibitors. COX-2 expression was measured in human melanoma cell lines A2058 and MelJuso by immunocytochemistry and immunoblotting. Cellular uptake experiments using varying C1 concentrations down to 0.

Expression of the human endogenous retrovirus (HERV) group HML-2/HERV-K does not depend on canonical promoter elements but is regulated by transcription factors Sp1 and Sp3.

After fixation in the human genome, human endogenous retroviruses (HERVs) are bona fide cellular genes despite their exogenous origin. To be able to spread within the germ line and the early embryo, the ancient retroviral promoters must have adapted to the requirements for expression in these cell types. We describe that in contrast to the case for current exogenous retroviruses, which replicate in specific somatic cells, the long terminal repeat (LTR) of the human endogenous retrovirus HERV-K acts as a TATA- and initiator element-independent promoter with a variable transcription start site.

Serological response to human endogenous retrovirus K in melanoma patients correlates with survival probability.

A few years ago, reactivation of human endogenous retrovirus K (HERV-K) proviruses in melanoma was described. The expression of HERV-K proteins induces humoral immune responses. The aim of the present study was to elucidate the prognostic relevance of serological anti-HERV-K reactivity in melanoma patients.