Modular binder technology by NGS-aided, high-resolution selection in yeast of designed armadillo modules.

Establishing modular binders as diagnostic detection agents represents a cost- and time-efficient alternative to the commonly used binders that are generated one molecule at a time. In contrast to these conventional approaches, a modular binder can be designed in silico from individual modules to, in principle, recognize any desired linear epitope without going through a selection and hit-validation process, given a set of preexisting, amino acid-specific modules. Designed armadillo repeat proteins (dArmRP) have been developed as modular binder scaffolds, and we report here the generation of highly specific dArmRP modules by yeast surface display selection, performed on a rationally designed dArmRP library.

Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results.

Background: Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells.

Reduction in surgical site infections by localized administration with D-PLEX in patients with multiple risk factors undergoing colorectal surgery.

Background: D-PLEX is a novel drug-eluting lipid polymer matrix that supplies a high, local concentration of doxycycline for approximately 30 days. The objective of this post-hoc analysis was to assess the efficacy of D-PLEX in preventing superficial and deep SSIs in patients with ≥2 risk factors.

Patients And Methods: A post-hoc analysis of a previously reported prospective randomized trial assessing D-PLEX plus Standard of Care (SOC) versus SOC alone in colorectal surgery was performed to assess SSI rate in patients with ≥2 risk factors.

A prospective, randomized assessment of a novel, local antibiotic releasing platform for the prevention of superficial and deep surgical site infections.

Background: Despite significant advances in infection control guidelines and practices, surgical site infections (SSIs) remain a substantial cause of morbidity, prolonged hospitalization, and mortality among patients having both elective and emergent surgeries. D-PLEX is a novel, antibiotic-eluting polymer-lipid matrix that supplies a high, local concentration of doxycycline for the prevention of superficial and deep SSIs. The aim of our study was to evaluate the safety and efficacy of D-PLEX in addition to standard of care (SOC) in preventing superficial and deep surgical site infections for patients undergoing elective colorectal surgery.

Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study.

Objective: Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS).

Methods: Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc.

Local prolonged release of antibiotic for prevention of sternal wound infections postcardiac surgery-A novel technology.

Introduction: Sternal wound infection (SWI) is a devastating postcardiac surgical complication. D-PLEX (D-PLEX) is a localized prolonged release compound applied as a prophylactic at the completion of surgery to prevent SWI. The D-PLEX technology platform is built as a matrix of alternating layers of polymers and lipids, entrapping an antibiotic (doxycycline).

Interim Results of the Remede d'Or Study: A Multicenter, Single-Blind, Randomized, Controlled Trial to Assess the Safety and Efficacy of an Innovative Topical Formulation of Erythropoietin for Treating Diabetic Foot Ulcers.

To inform on the interim results of the Remede d'Or study, which is a prospective, multicenter, single-blind, randomized, controlled clinical study on the safety and efficacy of RMD-G1, a topical carbopol-based hydrogel with a fibronectin matrix whose active pharmaceutical ingredient is erythropoietin (EPO), for treating diabetic foot ulcers (DFU). The trial will comprise 20 patients with type 2 diabetes mellitus with neuroischemic DFUs who will be randomized into two groups: (1) a control group in which standard-of-care (SOC) will be used to treat the DFUs, and (2) a test group in which SOC and RMD-G1 will be used to treat the DFUs. On day 0, all participants will be randomized to receive either RMD-G1 and SOC treatment or SOC alone.

Intestinal ischemia-reperfusion leads to early systemic micro-rheological and multiorgan microcirculatory alterations in the rat.

Background: Intestinal ischemia-reperfusion (I/R) is a potentially life-threatening situation and its pathomechanism is not fully understood yet.

Objective: To investigate the early micro-rheological, microcirculatory and morphological consequences of intestinal I/R in a rat model.

Methods: CD rats were anesthetized and subjected to Control (n = 7) or I/R (n = 7) groups.

Whole Cell Panning with Phage Display.

Phage display has emerged as one of the leading technologies for the selection of highly specific monoclonal antibodies, offering a number of advantages over traditional methods of antibody generation. While there are various possibilities to conduct phage display (e.g.

Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson's Disease.

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success.

Comparative laboratory evolution of ordered and disordered enzymes.

Intrinsically disordered proteins are ubiquitous in nature. To assess potential evolutionary advantages and disadvantages of structural disorder under controlled laboratory conditions, we directly compared the evolvability of weakly active ordered and disordered variants of dihydrofolate reductase by genetic selection. The circularly permuted Escherichia coli enzyme, which exists as a molten globule in the absence of ligands, and a well folded deletion mutant of the Bacillus stearothermophilus enzyme served as starting points.

A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties.

This report describes the design, generation and testing of Ylanthia, a fully synthetic human Fab antibody library with 1.3E+11 clones. Ylanthia comprises 36 fixed immunoglobulin (Ig) variable heavy (VH)/variable light (VL) chain pairs, which cover a broad range of canonical complementarity-determining region (CDR) structures.

HuCAL PLATINUM, a synthetic Fab library optimized for sequence diversity and superior performance in mammalian expression systems.

This article describes the design of HuCAL (human combinatorial antibody library) PLATINUM, an optimized, second-generation, synthetic human Fab antibody library with six trinucleotide-randomized complementarity-determining regions (CDRs). Major improvements regarding the optimized antibody library sequence space were implemented. Sequence space optimization is considered a multistep process that includes the analysis of unproductive antibody sequences in order to, for example, avoid motifs such as potential N-glycosylation sites, which are undesirable in antibody production.

Fiber scaffolds of polysialic acid via electrospinning for peripheral nerve regeneration.

Fiber scaffolds of bioactive polysialic acid have been prepared via electrospinning for peripheral nerve regeneration. The diameter, morphology and alignment of fibers in scaffolds were adjusted by variation of electrospinning parameters, which are decisive for the cell-scaffold interaction. Due to the high water solubility of polysialic acid (poly-alpha-2,8-N-acetylneuraminic acid) a photoactive derivative (poly-alpha-2,8-N-pentenoylneuraminic acid) was used to obtain stable fiber scaffolds in water by photochemical crosslinking.

Polysialic acid immobilized on silanized glass surfaces: a test case for its use as a biomaterial for nerve regeneration.

The immobilization of polysialic acid (polySia) on glass substrates has been investigated with regard to the applicability of this polysaccharide as a novel, biocompatible and bioresorbable material for tissue engineering, especially with regard to its use in nerve regeneration. PolySia, a homopolymer of alpha-2,8-linked sialic acid, is involved in post-translational modification of the neural cell adhesion molecule (NCAM). The degradation of polySia can be controlled which makes it an interesting material for coating and for scaffold construction in tissue engineering.

Rolled-up three-dimensional metamaterials with a tunable plasma frequency in the visible regime.

We propose and realize a novel concept of a self-organized three-dimensional metamaterial with a plasma frequency in the visible regime. We utilize the concept of self-rolling strained layers to roll up InGaAs/GaAs/Ag multilayers with multiple rotations. The walls of the resulting tubes represent a radial superlattice with a tunable layer thickness ratio and lattice constant.

Synthesis and biological evaluation of a polysialic acid-based hydrogel as enzymatically degradable scaffold material for tissue engineering.

Restorative medicine has a constant need for improved scaffold materials. Degradable biopolymers often suffer from uncontrolled chemical or enzymatic hydrolysis by the host. The need for a second surgery on the other hand is a major drawback for nondegradable scaffold materials.

Fab MOR03268 triggers absorption shift of a diagnostic dye via packaging in a solvent-shielded Fab dimer interface.

Molecular interactions between near-IR fluorescent probes and specific antibodies may be exploited to generate novel smart probes for diagnostic imaging. Using a new phage display technology, we developed such antibody Fab fragments with subnanomolar binding affinity for tetrasulfocyanine, a near-IR in vivo imaging agent. Unexpectedly, some Fabs induced redshifts of the dye absorption peak of up to 44 nm.

The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies.

This article describes the generation of the Human Combinatorial Antibody Library HuCAL GOLD. HuCAL GOLD is a synthetic human Fab library based on the HuCAL concept with all six complementarity-determining regions (CDRs) diversified according to the sequence and length variability of naturally rearranged human antibodies. The human antibody repertoire was analyzed in-depth, and individual CDR libraries were designed and generated for each CDR and each antibody family.

Collagen biomaterial doped with colominic acid for cell culture applications with regard to peripheral nerve repair.

Colominic acid (CA) is a homopolymer of sialic acid residues and is solely composed of polymerised units of alpha-2,8-linked N-acetylneuraminic acid. CA is a specific derivative of polysialic acid (PSA), produced as the capsular polysaccharide of Escherichia coli K1 derived molecule of PSA. PSA in vivo plays a significant role in synaptic plasticity and neural development.

A study on polysialic acid as a biomaterial for cell culture applications.

Polysialic acid (PSA) was investigated for its applicability as coating material for mammalian cell cultivation. PSA is involved in post-translational modification of the vertebrate neural cell adhesion molecule (NCAM). It is biocompatible and degradation-controlled.

Crystallization and molecular-replacement solution of a diagnostic fluorescent dye in complex with a specific Fab fragment.

Tetrasulfocyanine (TSC) has been described as a fluorescent probe for tumour imaging. The complex of TSC and the Fab antibody fragment MOR03268 has been crystallized in three different crystal forms. MOR03268 was identified from the HuCAL GOLD library and further optimized to bind TSC with high affinity (Kd = 0.

Fast and efficient screening system for new biomaterials in tissue engineering: a model for peripheral nerve regeneration.

The use of three-dimensional biodegradable matrices is one major issue in tissue engineering. Numerous materials, fabrication techniques, and modifications have been used and tested in different areas of tissue engineering recently. But nevertheless, technology is far from being optimized and optimal constructs with bioidentical and mechanical properties have not been described in the literature so far.

Application of collagen matrices for cartilage tissue engineering.

Articular cartilage shows little capacity for self-repair once it has been damaged. The aim of this study was to investigate different collagen matrices regarding their applicability for cartilage tissue engineering. The matrices consist of collagen I and small amounts of elastine, were crosslinked with carbodiimide or glucose.