Correction: 3D printed and stimulus responsive drug delivery systems based on synthetic polyelectrolyte hydrogels manufactured via digital light processing.

Correction for '3D printed and stimulus responsive drug delivery systems based on synthetic polyelectrolyte hydrogels manufactured via digital light processing' by Sonja Vaupel et al., J. Mater. Chem. B, 2023, DOI: https://doi.org/10.1039/d3tb00285c.

3D printed and stimulus responsive drug delivery systems based on synthetic polyelectrolyte hydrogels manufactured via digital light processing.

Hydrogels are three-dimensional hydrophilic polymeric networks absorbing up to and even more than 90 wt% of water. These superabsorbent polymers retain their shape during the swelling process while enlarging their volume and mass. In addition to their swelling behavior, hydrogels can possess other interesting properties, such as biocompatibility, good rheological behavior, or even antimicrobial activity. This versatility qualifies hydrogels for many medical applications, especially drug delivery systems. As recently shown, polyelectrolyte-based hydrogels offer beneficial properties for long-term and stimulus-responsive applications. However, the fabrication of complex structures and shapes can be difficult to achieve with common polymerization methods. This obstacle can be overcome by the use of additive manufacturing. 3D printing technology is gaining more and more attention as a method of producing materials for biomedical applications and medical devices. Photopolymerizing 3D printing methods offer superior resolution and high control of the photopolymerization process, allowing the fabrication of complex and customizable designs while being less wasteful. In this work, novel synthetic hydrogels, consisting of [2-(acryloyloxy) ethyl]trimethylammonium chloride (AETMA) as an electrolyte monomer and poly(ethylene glycol)-diacrylate (PEGDA) as a crosslinker, 3D printed via Digital Light Processing (DLP) using a layer height of 100 µm, are reported. The hydrogels obtained showed a high swelling degree q∞m,t ∼ 12 (24 h in PBS; pH 7; 37 °C) and adjustable mechanical properties with high stretchability (εmax ∼ 300%). Additionally, we embedded the model drug acetylsalicylic acid (ASA) and investigated its stimulus-responsive drug release behaviour in different release media. The stimulus responsiveness of the hydrogels is mirrored in their release behavior and could be exploited in triggered as well as sequential release studies, demonstrating a clear ion exchange behavior. The received 3D-printed drug depots could also be printed in complex hollow geometry, exemplarily demonstrated via an individualized frontal neo-ostium implant prototype. Consequently, a drug-releasing, flexible, and swellable material was obtained, combining the best of both worlds: the properties of hydrogels and the ability to print complex shapes.

B(C6F5)3-Catalyzed transfer hydrogenation of esters and organic carbonates towards alcohols with ammonia borane.

Herein, we report an efficient metal-free system for the transfer hydrogenation of esters and carbonates by-passing the otherwise ubiquitous formation of transesterification side-products. The Lewis acid B(C6F5)3 is used as catalyst and ammonia borane as hydrogen donor. This methodology shows broad substrate scope and functional group tolerance in excellent yields at very mild conditions.

Swelling and Mechanical Characterization of Polyelectrolyte Hydrogels as Potential Synthetic Cartilage Substitute Materials.

Hydrogels have become an increasingly interesting topic in numerous fields of application. In addition to their use as immobilization matrixes in (bio)catalysis, they are widely used in the medical sector, e.g., in drug delivery systems, contact lenses, biosensors, electrodes, and tissue engineering. Cartilage tissue engineering hydrogels from natural origins, such as collagen, hyaluronic acid, and gelatin, are widely known for their good biocompatibility. However, they often lack stability, reproducibility, and mechanical strength. Synthetic hydrogels, on the other hand, can have the advantage of tunable swelling and mechanical properties, as well as good reproducibility and lower costs. In this study, we investigated the swelling and mechanical properties of synthetic polyelectrolyte hydrogels. The resulting characteristics such as swelling degree, stiffness, stress, as well as stress-relaxation and cyclic loading behavior, were compared to a commercially available biomaterial, the ChondroFiller® liquid, which is already used to treat articular cartilage lesions. Worth mentioning are the observed good reproducibility and high mechanical strength of the synthetic hydrogels. We managed to synthesize hydrogels with a wide range of compressive moduli from 2.5 ± 0.1 to 1708.7 ± 67.7 kPa, which addresses the span of human articular cartilage.

Swelling and Diffusion in Polymerized Ionic Liquids-Based Hydrogels.

Hydrogels are one of the emerging classes of materials in current research. Besides their numerous applications in the medical sector as a drug delivery system or in tissue replacement, they are also suitable as irrigation components or as immobilization matrices in catalysis. For optimal application of these compounds, knowledge of the swelling properties and the diffusion mechanisms occurring in the gels is mandatory. This study is focused on hydrogels synthesized by radical polymerization of imidazolium-based ionic liquids. Both the swelling and diffusion behavior of these hydrogels were investigated via gravimetric swelling as well as sorption experiments implemented in water, ethanol, n-heptane, and tetrahydrofuran. In water and ethanol, strong swelling was observed while the transport mechanism deviated from Fickian-type behavior. By varying the counterion and the chain length of the cation, their influences on the processes were observed. The calculation of the diffusion coefficients delivered values in the range of 10-10 to 10-12 m2 s-1. The gravimetric results were supported by apparent diffusion coefficients measured through diffusion-weighted magnetic resonance imaging. A visualization of the water diffusion front within the hydrogel should help to further elucidate the diffusion processes in the imidazolium-based hydrogels.

UV-Polymerized Vinylimidazolium Ionic Liquids for Permselective Membranes.

Ionic liquids are highly charged compounds with increasing applications in material science. A universal approach to synthesize free-standing, vinylalkylimidazolium bromide-containing membranes with an adjustable thickness is presented. By the variation of alkyl side chains, membrane characteristics such as flux and mechanical properties can be adjusted. The simultaneous use of different ionic liquids (ILs) in the synthesis can also improve the membrane properties. In separation application, these charged materials allowed us to retain charged sugars, such as calcium gluconate, by up to 95%, while similar neutral compounds such as glucose passed the membrane. An analysis of the surface conditions using atomic force microscopy (AFM) confirmed the experimental data and explains the decreasing permeance and increased retention of the charged sugars.

Ion Exchange Controlled Drug Release from Polymerized Ionic Liquids.

In this work ion functionalized hydrogels as potent drug delivery systems are presented. The ion functionalization of the hydrogel enables the retention of ionic drug molecules and thus a reduction of burst release effects. Timolol maleate in combination with polymerized anionic 3-sulfopropylmethacrylate potassium and ibuprofen combined with cationic poly-[2-(methacryloyloxy)ethyl] trimethylammonium chloride are investigated in respect to their drug release profile. The results are showing an ion exchange depending release behavior instead of a diffusion-controlled drug release as it is known from common drug delivery systems. Furthermore, the suitability of such hydrogels for standard methods for sterilization is investigated.

The Role of Reaction Engineering in Bioprocess Development.

This short review highlights the role of reaction engineering as a tool for bioprocess development. Selected examples are discussed that demonstrate the need to understand thermodynamic and kinetic properties of the reaction system in order to identify potential bottlenecks. For coupled enzyme systems and reaction cascades modelling as well as selection of suitable reactor configurations is discussed. For the problem of overcoming product inhibition examples are given, followed by selected examples for in situ product removal. Finally, two reactor concepts for oxidation reactions requiring oxygen are briefly presented.

Swelling characteristics and biocompatibility of ionic liquid based hydrogels for biomedical applications.

Polymers are commonly used in medical device manufacturing, e.g. for drug delivery systems, bone substitutes and stent coatings. Especially hydrogels exhibit very promising properties in this field. Hence, the development of new hydrogel systems for customized application is of great interest, especially regarding the swelling behavior and mechanical properties as well as the biocompatibility. The aim of this work was the preparation and investigation of various polyelectrolyte and poly-ionic liquid based hydrogels accessible by radical polymerization. The obtained polymers were covalently crosslinked with N,N'-methylenebisacrylamide (MBAA) or different lengths of poly(ethyleneglycol)diacrylate (PEGDA). The effect of different crosslinker-to-monomer ratios has been examined. In addition to the compression curves and the maximum degree of swelling, the biocompatibility with L929 mouse fibroblasts of these materials was determined in direct cell seeding experiments and the outcome for the different hydrogels was compared.

Coagulation using organic carbonates opens up a sustainable route towards regenerated cellulose films.

Due to their biodegradability, biocompatibility and sustainable nature, regenerated cellulose (RC) films are of enormous relevance for green applications including medicinal, environmental and separation technologies. However, the processes used so far are very hazardous to the environment and health. Here, we disclose a simple, fast, environmentally friendly, nontoxic and cost-effective processing method for preparing RC films. High quality non-transparent and transparent RC films and powders can be produced by dissolution with tetrabutylphosphonium hydroxide [TBPH]/[TBP]+[OH]- followed by coagulation with organic carbonates. Investigations on the coagulation mechanism revealed an extremely fast reaction between the carbonates and the hydroxide ions. The high-quality powders and films were fully characterized with respect to structure, surface morphology, permeation and selectivity. This method represents a future-oriented green alternative to known industrial processes.

Synthesis of novel carbohydrate based pyridinium ionic liquids and cytotoxicity of ionic liquids for mammalian cells.

The large pool of naturally occurring carbohydrates with their diversity in chirality and structure led to the idea of a systematic investigation of carbohydrate based ILs. To this end, we investigated the influence of different ether groups, mainly methyl or ethyl ether, on the secondary OH groups as well as different configurations on physical properties such as melting point, thermostability and especially the influence on cell toxicity. For this investigation we chose α- and ß-methyl-, ß-allyl- and ß-phenyl d-glucopyranose as well as four 1-deoxy-pentoses. In order to be able to classify the results, more ionic liquids with different structural motives were examined for cytotoxicity. Here, we present data that confirm the biocompatibility of such ILs consisting of naturally occurring molecules or their derivatives. The synthesized carbohydrate based ILs were tested for their suitability as additives in coatings for medical applications such as drug-eluting balloons.

Low-Melting Manganese (II)-Based Ionic Liquids: Syntheses, Structures, Properties and Influence of Trace Impurities.

The synthesis of more than 10 new magnetic ionic liquids with [MnX4]2- anions, X = Cl, NCS, NCO, is presented. Detailed structural information through single-crystal X-ray diffraction is given for (DMDIm)[Mn(NCS)4], (BnEt3N)2[Mn(NCS)4], and {(Ph3P)2N}2[Mn(NCO4)]·0.6H2O, respectively. All compounds consist of discrete anions and cations with tetrahedrally coordinated Mn (II) atoms. They show paramagnetic behavior as expected for spin-only systems. Melting points are found for several systems below 100 °C classifying them as ionic liquids. Thermal properties are investigated using differential scanning calorimetry (DSC) measurements. The physicochemical properties of density, dynamic viscosity, electrolytic conductivity, and surface tension were measured temperature-dependent of selected samples. These properties are discussed in comparison to similar Co containing systems. An increasing amount of bromide impurity is found to affect the surface tension only up to 3.3%.

Development of Ionic Liquid-Water-Based Thermomorphic Solvent (TMS)-Systems for Biocatalytic Reactions.

The applicability of ionic liquid-water-based thermomorphic solvent (TMS)-systems with an upper critical solution temperature for homogeneous biocatalysis is investigated. Cholinium- and imidazolium-based ionic liquids are used to facilitate a temperature-dependent phase change, which can be easily fine-tuned by adding salts or polar organic solvents. Within the TMS-system, a high enzymatic activity and subsequent full conversion is achieved in the intermittent monophasic reaction system of the TMS-system. Therefore, the biocatalyst can be easily recycled after separating the phases at lower temperatures.

The Effect of Additives on the Viscosity and Dissolution of Cellulose in Tetrabutylphosphonium Hydroxide.

An electrolyte solution of tetrabutylphosphonium hydroxide (TBPH) in water can dissolve over 20 wt % of cellulose in minutes and therefore constitutes a promising alternative green solvent system compared to known imidazolium- or dimethylacetamide-based systems. Overcoming the disadvantage of the extremely high viscosity of TBPH/cellulose solutions can facilitate their use for various applications. In this study, the application of cosolvents for the reduction, and thus adjustability, of the viscosity is addressed. Even well-known antisolvents can be easily deployed, resulting in a dramatic drop in viscosity. High concentrations of cosolvents (excluding ethanol) are tolerated without precipitation of the dissolved cellulose. Furthermore, the effect of the cosolvents on the additional dissolution of cellulose is discussed. The amount of dissolved cellulose is quantified by 13 C NMR spectroscopy.

Role of endoplasmic reticulum stress and protein misfolding in disorders of the liver and pancreas.

The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. The fraction of protein passing through the ER represents a large proportion of the total protein in the cell. Protein folding, glycosylation, sorting and transport are essential tasks of the ER and a compromised ER folding network has been recognized to be a key component in the disease pathogenicity of common neurodegenerative, metabolic and malignant diseases. On the other hand, the ER protein folding machinery also holds significant potential for therapeutic interventions. Many causes can lead to ER stress. A disturbed calcium homeostasis, the generation of reactive oxygen species (ROS) and a persistent overload of misfolded proteins within the ER can drive the course of adisease. In this review the role of ER-stress in diseases of the liver and pancreas will be examined using pancreatitis and Wilson´s disease as examples. Potential therapeutic targets in ER-stress pathways will also be discussed.

Effects of a common pharmaceutical, atorvastatin, on energy metabolism and detoxification mechanisms of a marine bivalve Mytilus edulis.

Biologically active compounds from pharmaceuticals cause concern due to their common occurrence in water and sediments of urbanized coasts and potential threat to marine organisms. Atorvastatin (ATO), a globally prescribed drug, is environmentally stable and bioavailable to marine organisms; however, the physiological and toxic effects of this drug on ecologically important coastal species are yet to be elucidated. We studied the effect of ATO (˜1.2 µg L-1) on bioenergetics (including whole-organism and mitochondrial respiration, as well as tissue energy reserves and mRNA expression of genes involved in mitochondrial biogenesis and fatty acid metabolism in the gills and the digestive gland) of a keystone bivalve Mytulis edulis (the blue mussel) from the Baltic Sea. Xenobiotic detoxification systems including activity and mRNA expression of P-glycoprotein, and Phase I and II biotransformation enzymes (cytochrome P450 monooxygenase CYP1A and glutathione transferase, GST) were also assessed in the gill and digestive gland of the mussels. Exposure to ATO caused rapid uptake and biotransformation of the drug by the mussels. Standard metabolic rate of ATO-exposed mussels increased by 56% indicating higher maintenance costs, yet no changes were detected in the respiratory capacity of isolated mitochondria. ATO exposure led to ˜60% decrease in the lysosomal membrane stability of hemocytes and ˜3-fold decrease in the whole-organism P-glycoprotein-driven and diffusional efflux of xenobiotics indicating altered membrane properties. The digestive gland was a major target of ATO toxicity in the mussels. Exposure of mussels to ATO led to depletion of lipid, carbohydrate and protein pools, and suppressed transcription of key enzymes involved in mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC-1α) and fatty acid metabolism (acetyl-CoA carboxylase and CYP4Y1) in the digestive gland. No bioenergetic disturbances were observed in the gills of ATO-exposed mussels, and elevated GST activity indicated enhanced ATO detoxification in this tissue. These data demonstrate that ATO can act as a metabolic disruptor and chemosensitizer in keystone marine bivalves and warrant further investigations of statins as emerging pollutants of concern in coastal marine ecosystems.

Quantification of amino acids and peptides in an ionic liquid based aqueous two-phase system by LC-MS analysis.

Aqueous two-phase systems (ATPS) occur by the mixture of two polymers or a polymer and an inorganic salt in water. It was shown that not only polymers but also ionic liquids in combination with inorganic cosmotrophic salts are able to build ATPS. Suitable for the formation of ionic liquid-based ATPS systems are hydrophilic water miscible ionic liquids. To understand the driving force for amino acid and peptide distribution in IL-ATPS at different pH values, the ionic liquid Ammoeng 110™ and K2HPO4 have been chosen as a test system. To quantify the concentration of amino acids and peptides in the different phases, liquid chromatography and mass spectrometry (LC-MS) technologies were used. Therefore the peptides and amino acids have been processed with EZ:faast™-Kit from Phenomenex for an easy and reliable quantification method even in complex sample matrices. Partitioning is a surface-dependent phenomenon, investigations were focused on surface-related amino acid respectively peptide properties such as charge and hydrophobicity. Only a very low dependence between the amino acids or peptides hydrophobicity and the partition coefficient was found. Nevertheless, the presented results show that electrostatic respectively ionic interactions between the ionic liquid and the amino acids or peptides have a strong impact on their partitioning behavior.

Recent developments in biocatalysis in multiphasic ionic liquid reaction systems.

Ionic liquids are well known and frequently used 'designer solvents' for biocatalytic reactions. This review highlights recent achievements in the field of multiphasic ionic liquid-based reaction concepts. It covers classical biphasic systems including supported ionic liquid phases, thermo-regulated multi-component solvent systems (TMS) and polymerized ionic liquids. These powerful concepts combine unique reaction conditions with a high potential for future applications on a laboratory and industrial scale. The presence of a multiphasic system simplifies downstream processing due to the distribution of the catalyst and reactants in different phases.

Recent Developments in the Preparation of Silicones with Antimicrobial Properties.

This Focus Review describes state-of-the-art methods for the preparation of antimicrobial silicones. Given the diversity of antimicrobial activity and their mechanisms, the performance of these materials is highly dependent on the characteristics of the polymeric matrix. Therefore, different synthetic routes have been developed, such as 1) physical treatments, 2) chemical transformations, and 3) copolymerization. This classification is not exclusive, so some products belong to more than one class. Herein, we attempt to present a handy overview of the development of antimicrobial silicones, their most important application fields, the most relevant antimicrobial assays, and, as the title suggests, an overview of the most relevant preparation methods.

Simple and Effective Catalyst Separation by New CO2 -Induced Switchable Organocatalysts.

CO2 -induced switchable tertiary amine-based organocatalysts were investigated for an efficient catalyst and product separation by its different partitioning between an organic and carbonated water phase. In this case study, the switching ability of eight tertiary amine-based catalysts between the organic and water phase by addition or removal of CO2 was investigated. Here, the catalyst switched both nearly completely (99.9 %) into the aqueous phase by addition of CO2 and effectively back into the organic phase (99.3 %) by expelling CO2 . With this technique, the organocatalyst was successfully recovered and reused twelve times without significant loss of activity (up to 90 % enantiomeric excess) for the asymmetric nitroaldol (Henry) reaction. After the first catalyst switch, evaporation of the solvent affords the product in 98 % purity without any further purification steps.