by Keyword: Polymerization

Witzdam, L, Vosberg, B, Grosse-Berkenbusch, K, Stoppelkamp, S, Wendel, HP, Rodriguez-Emmenegger, C, (2024). Tackling the Root Cause of Surface-Induced Coagulation: Inhibition of FXII Activation to Mitigate Coagulation Propagation and Prevent Clotting Macromolecular Bioscience 24, e2300321

Factor XII (FXII) is a zymogen present in blood that tends to adsorb onto the surfaces of blood-contacting medical devices. Once adsorbed, it becomes activated, initiating a cascade of enzymatic reactions that lead to surface-induced coagulation. This process is characterized by multiple redundancies, making it extremely challenging to prevent clot formation and preserve the properties of the surface. In this study, a novel modulatory coating system based on C1-esterase inhibitor (C1INH) functionalized polymer brushes, which effectively regulates the activation of FXII is proposed. Using surface plasmon resonance it is demonstrated that this coating system effectively repels blood plasma proteins, including FXII, while exhibiting high activity against activated FXII and plasma kallikrein under physiological conditions. This unique property enables the modulation of FXII activation without interfering with the overall hemostasis process. Furthermore, through dynamic Chandler loop studies, it is shown that this coating significantly improves the hemocompatibility of polymeric surfaces commonly used in medical devices. By addressing the root cause of contact activation, the synergistic interplay between the antifouling polymer brushes and the modulatory C1INH is expected to lay the foundation to enhance the hemocompatibility of medical device surfaces.© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.

JTD Keywords: adsorption, binding, c1-esterase-inhibitor, coatings, contact activation, factor-xii, fxii activation, hemocompatibility, hemocompatible surface modification, heparin, polymer brushes, system, thrombosis, Adsorption, Anticoagulation, Antifouling agent, Article, Beta-fxiia, Biocompatibility, Blood, Blood clotting, Blood clotting factor 12, Blood clotting factor 12a, Blood clotting factor 12a inhibitor, Blood coagulation, C1-esterase-inhibitor, Cell activation, Chemical activation, Coagulation, Coating (procedure), Complement component c1s inhibitor, Complement system, Controlled study, Dendrimers, Enzyme immobilization, Enzymes, Erythrocyte, Esters, Factor xii, Factor xii activation, Factor xiia, Fibrin deposition, Functional polymers, Fxii activation, Haemocompatibility, Hemocompatibility, Hemocompatible surface modification, Hemostasis, Heparin, Human, Hydrogel, Medical devices, Metabolism, Plasma kallikrein, Plasma protein, Plastic coatings, Platelet count, Polymer, Polymer brushes, Polymerization, Polymers, Property, Root cause, Surface plasmon resonance, Surface property, Surface reactions, Surface-modification, Thrombocyte adhesion, Β-fxiia

Sortino, Rosalba, Cunquero, Marina, Castro-Olvera, Gustavo, Gelabert, Ricard, Moreno, Miquel, Riefolo, Fabio, Matera, Carlo, Fernandez-Castillo, Noelia, Agnetta, Luca, Decker, Michael, Lluch, Jose M, Hernando, Jordi, Loza-Alvarez, Pablo, Gorostiza, Pau, (2023). Three-Photon Infrared Stimulation of Endogenous Neuroreceptors in Vivo Angewandte Chemie (International Ed. Print) 62, e202311181

To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using genetic or pharmacological specificity. This challenge requires deep penetration and focusing as provided by infrared light and multiphoton excitation, and has promoted two-photon photopharmacology and optogenetics. However, three-photon brain stimulation in vivo remains to be demonstrated. We report the regulation of neuronal activity in zebrafish larvae by three-photon excitation of a photoswitchable muscarinic agonist at 50 pM, a billion-fold lower concentration than used for uncaging, and with mid-infrared light of 1560 nm, the longest reported photoswitch wavelength. Robust, physiologically relevant photoresponses allow modulating brain activity in wild-type animals with spatiotemporal and pharmacological precision. Computational calculations predict that azobenzene-based ligands have high three-photon absorption cross-section and can be used directly with pulsed infrared light. The expansion of three-photon pharmacology will deeply impact basic neurobiology and neuromodulation phototherapies.© 2023 Wiley-VCH GmbH.

JTD Keywords: absorption, azobenzene photoswitches, deep, glutamate-receptor, intravital microscopy, multiphoton excitation, muscarinic neuromodulation, photopharmacology, two-photon lithography and polymerization, 2-photon excitation, Azobenzene, Multiphoton excitation, Muscarinic neuromodulation, Photopharmacology, Photopharmacology, azobenzene, muscarinic neuromodulation, multiphoton excitation, two-photon lithography and polymerization, Two-photon lithography and polymerization

Prischich, D, Camarero, N, del Dedo, JE, Cambra-Pellejà, M, Prat, J, Nevola, L, Martín-Quirós, A, Rebollo, E, Pastor, L, Giralt, E, Geli, MI, Gorostiza, P, (2023). Light-dependent inhibition of clathrin-mediated endocytosis in yeast unveils conserved functions of the AP2 complex Iscience 26, 107899

Clathrin-mediated endocytosis (CME) is an essential cellular process, conserved among eukaryotes. Yeast constitutes a powerful genetic model to dissect the complex endocytic machinery, yet there is a lack of specific pharmacological agents to interfere with CME in these organisms. TL2 is a light-regulated peptide inhibitor targeting the AP2-β-adaptin/β-arrestin interaction and that can photocontrol CME with high spatiotemporal precision in mammalian cells. Here, we study endocytic protein dynamics by live-cell imaging of the fluorescently tagged coat-associated protein Sla1-GFP, demonstrating that TL2 retains its inhibitory activity in S. cerevisiae spheroplasts. This is despite the β-adaptin/β-arrestin interaction not being conserved in yeast. Our data indicate that the AP2 α-adaptin is the functional target of activated TL2. We identified as interacting partners for the α-appendage, the Eps15 and epsin homologues Ede1 and Ent1. This demonstrates that endocytic cargo loading and sensing can be executed by conserved molecular interfaces, regardless of the proteins involved.© 2023 The Author(s).

JTD Keywords: adapters, alpha-appendage, azobenzene, cross-linker, mechanism, peptides, proteins, receptor, trafficking, Actin polymerization, Biochemistry, Biological sciences, Cell biology, Molecular biology, Natural sciences

Macedo, MH, Torras, N, García-Díaz, M, Barrias, C, Sarmento, B, Martínez, E, (2023). The shape of our gut: Dissecting its impact on drug absorption in a 3D bioprinted intestinal model Biomaterials Advances 153, 213564

The small intestine is a complex organ with a characteristic architecture and a major site for drug and nutrient absorption. The three-dimensional (3D) topography organized in finger-like protrusions called villi increases surface area remarkably, granting a more efficient absorption process. The intestinal mucosa, where this process occurs, is a multilayered and multicell-type tissue barrier. In vitro intestinal models are routinely used to study different physiological and pathological processes in the gut, including compound absorption. Still, standard models are typically two-dimensional (2D) and represent only the epithelial barrier, lacking the cues offered by the 3D architecture and the stromal components present in vivo, often leading to inaccurate results. In this work, we studied the impact of the 3D architecture of the gut on drug transport using a bioprinted 3D model of the intestinal mucosa containing both the epithelial and the stromal compartments. Human intestinal fibroblasts were embedded in a previously optimized hydrogel bioink, and enterocytes and goblet cells were seeded on top to mimic the intestinal mucosa. The embedded fibroblasts thrived inside the hydrogel, remodeling the surrounding extracellular matrix. The epithelial cells fully covered the hydrogel scaffolds and formed a uniform cell layer with barrier properties close to in vivo. In particular, the villus-like model revealed overall increased permeability compared to a flat counterpart composed by the same hydrogel and cells. In addition, the efflux activity of the P-glycoprotein (P-gp) transporter was significantly reduced in the villus-like scaffold compared to a flat model, and the genetic expression of other drugs transporters was, in general, more relevant in the villus-like model. Globally, this study corroborates that the presence of the 3D architecture promotes a more physiological differentiation of the epithelial barrier, providing more accurate data on drug absorbance measurements.Copyright © 2023. Published by Elsevier B.V.

JTD Keywords: 3d architecture, alkaline-phosphatase, caco-2 cells, culture, drug development, efflux proteins, gene-expression, human-colon, intestinal absorption, intestinal models, microenvironment, paracellular transport, permeability, photopolymerization, villi, 3d architecture, 3d bioprinting, Drug development, In-vitro, Intestinal absorption, Intestinal models, Photopolymerization, Villi

Quiroga, X, Walani, N, Disanza, A, Chavero, A, Mittens, A, Tebar, F, Trepat, X, Parton, RG, Geli, MI, Scita, G, Arroyo, M, Le Roux, AL, Roca-Cusachs, P, (2023). A mechanosensing mechanism controls plasma membrane shape homeostasis at the nanoscale Elife 12, e72316

As cells migrate and experience forces from their surroundings, they constantly undergo mechanical deformations which reshape their plasma membrane (PM). To maintain homeostasis, cells need to detect and restore such changes, not only in terms of overall PM area and tension as previously described, but also in terms of local, nanoscale topography. Here, we describe a novel phenomenon, by which cells sense and restore mechanically induced PM nanoscale deformations. We show that cell stretch and subsequent compression reshape the PM in a way that generates local membrane evaginations in the 100 nm scale. These evaginations are recognized by I-BAR proteins, which triggers a burst of actin polymerization mediated by Rac1 and Arp2/3. The actin polymerization burst subsequently re-flattens the evagination, completing the mechanochemical feedback loop. Our results demonstrate a new mechanosensing mechanism for PM shape homeostasis, with potential applicability in different physiological scenarios.© 2023, Quiroga et al.

JTD Keywords: arp2/3 complex, bar, bar proteins, cdc42, cells, domain, human, irsp53, membrane biophysics, mouse, proteins, rac, tension, Actin polymerization, Bar proteins, Cell biology, Human, Mechanobiology, Membrane biophysics, Mouse, Physics of living systems

Gholami, S, Rezvani, A, Vatanpour, V, Khoshravesh, SH, Llorens, J, Engel, E, Castano, O, Cortina, JL, (2023). Chlorine resistance property improvement of polyamide reverse osmosis membranes through cross-linking degree increment Science Of The Total Environment 889, 164283

Highly permeable polyamide reverse osmosis (RO) membranes are desirable for reducing the energy burden and ensuring future water resources in arid and semiarid regions. One notable drawback of thin film composite (TFC) polyamide RO/NF membranes is the polyamide's sensitivity to degradation by free chlorine, the most used biocide in water purification trains. This investigation demonstrated a significant increase in the crosslinking-degree parameter by the m-phenylenediamine (MPD) chemical structure extending in the thin film nanocomposite (TFN) membrane without adding extra MPD monomers to enhance the chlorine resistance and performance. Membrane modification was carried out according to monomer ratio changes and Nanoparticle embedding into the PA layer approaches. A new class of TFN-RO membranes incorporating novel aromatic amine functionalized (AAF)-MWCNTs embedded into the polyamide (PA) layer was introduced. A purposeful strategy was carried out to use cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) as an intermediate functional group in the AAF-MWCNTs. Thus, amidic nitrogen, connected to benzene rings and carbonyl groups, assembles a structure similar to the standard PA, consisting of MPD and trimesoyl chloride. The resulting AAF-MWCNTs were mixed in the aqueous phase during the interfacial polymerization to increase the susceptible positions to chlorine attack and improve the crosslinking degree in the PA network. The characterization and performance results of the membrane demonstrated an increase in ion selectivity and water flux, impressive stability of salt rejection after chlorine exposure, and improved antifouling performance. This purposeful modification resulted in overthrowing two tradeoffs; i) high crosslink density-water flux and ii) salt rejection-permeability. The modified membrane demonstrated ameliorative chlorine resistance relative to the pristine one, with twice the increase in crosslinking degree, more than four times the enhancement of the oxidation resistance, negligible reduction in the salt rejection (0.83 %), and only 5 L/m2.h flux loss following a rigorous static chlorine exposure of 500 ppm.h under acidic conditions. The excellent performance of new chlorine resistant TNF RO membranes fabricated via AAF-MWCNTs together with the facile membrane manufacturing process offered the possibility of postulating them in the desalination field, which could eventually help the current freshwater supply challenge.Copyright © 2023 Elsevier B.V. All rights reserved.

JTD Keywords: behavior, carbon nanotubes, desalination, interfacial polymerization, naclo resistance, nanocomposite, nanofiltration membrane, performance, polymerization, ro membranemodification, substrate, water, Antifouling, Desalination, Interfacial polymerization, Naclo resistance, Ro membrane modification, Thin-film composite

Venugopal, A, Ruiz-Perez, L, Swamynathan, K, Kulkarni, C, Calò, A, Kumar, M, (2023). Caught in Action: Visualizing Dynamic Nanostructures Within Supramolecular Systems Chemistry Angewandte Chemie (International Ed. Print) 62, e202208681

Supramolecular systems chemistry has been an area of active research to develop nanomaterials with life-like functions. Progress in systems chemistry relies on our ability to probe the nanostructure formation in solution. Often visualizing the dynamics of nanostructures which transform over time is a formidable challenge. This necessitates a paradigm shift from dry sample imaging towards solution-based techniques. We review the application of state-of-the-art techniques for real-time, in situ visualization of dynamic self-assembly processes. We present how solution-based techniques namely optical super-resolution microscopy, solution-state atomic force microscopy, liquid-phase transmission electron microscopy, molecular dynamics simulations and other emerging techniques are revolutionizing our understanding of active and adaptive nanomaterials with life-like functions. This Review provides the visualization toolbox and futuristic vision to tap the potential of dynamic nanomaterials.© 2022 Wiley-VCH GmbH.

JTD Keywords: electron-microscopy, fluorescence microscopy, in-situ, mechanical-properties, molecular simulations, nanostructures, polymerization, polymers, stimulated-emission, super-resolution microscopy, supramolecular chemistry, systems chemistry, water, Atomic-force microscopy, Liquid tem, Nanostructures, Super-resolution microscopy, Supramolecular chemistry, Systems chemistry

Elyaderani, AK, De Lama-Odría, MD, Del Valle, LJ, Puiggalí, J, (2022). Multifunctional Scaffolds Based on Emulsion and Coaxial Electrospinning Incorporation of Hydroxyapatite for Bone Tissue Regeneration International Journal Of Molecular Sciences 23, 15016

Tissue engineering is nowadays a powerful tool to restore damaged tissues and recover their normal functionality. Advantages over other current methods are well established, although a continuous evolution is still necessary to improve the final performance and the range of applications. Trends are nowadays focused on the development of multifunctional scaffolds with hierarchical structures and the capability to render a sustained delivery of bioactive molecules under an appropriate stimulus. Nanocomposites incorporating hydroxyapatite nanoparticles (HAp NPs) have a predominant role in bone tissue regeneration due to their high capacity to enhance osteoinduction, osteoconduction, and osteointegration, as well as their encapsulation efficiency and protection capability of bioactive agents. Selection of appropriated polymeric matrices is fundamental and consequently great efforts have been invested to increase the range of properties of available materials through copolymerization, blending, or combining structures constituted by different materials. Scaffolds can be obtained from different processes that differ in characteristics, such as texture or porosity. Probably, electrospinning has the greater relevance, since the obtained nanofiber membranes have a great similarity with the extracellular matrix and, in addition, they can easily incorporate functional and bioactive compounds. Coaxial and emulsion electrospinning processes appear ideal to generate complex systems able to incorporate highly different agents. The present review is mainly focused on the recent works performed with Hap-loaded scaffolds having at least one structural layer composed of core/shell nanofibers.

JTD Keywords: bone tissue, coaxial electrospinning, composite nanofibers, drug-release behavior, emulsion electrospinning, hydroxyapatite, in-vitro evaluation, mechanical-properties, osteogenic differentiation, pickering emulsions, protein adsorption, structured scaffolds, surface-initiated polymerization, tissue regeneration, Bone tissue, Coaxial electrospinning, Emulsion electrospinning, Hydroxyapatite, Multifunctional scaffolds, Poly(3-hydroxybutyrate) phb patches, Tissue regeneration

Pujals, S, Albertazzi, L, Fuentes, E, Gabaldon, Y, Collado, M, Dhiman, S, (2022). Supramolecular Stability of Benzene-1,3,5-tricarboxamide Supramolecular Polymers in Biological Media: Beyond the Stability-Responsiveness Trade-off Journal Of The American Chemical Society 144, 21196-21205

Supramolecular assemblies have been gaining attention in recent years in the field of drug delivery because of their unique formulation possibilities and adaptive behavior. Their non-covalent nature allows for their self-assembly formulation and responsiveness to stimuli, an appealing feature to trigger a therapeutic action with spatiotemporal control. However, facing in vivo conditions is very challenging for non-covalent structures. Dilution and proteins in blood can have a direct impact on self assembly, destabilizing the supramolecules and leading to a premature and uncontrolled cargo release. To rationalize this behavior, we designed three monomers exhibiting distinct hydrophobic cores that self-assemble into photo-responsive fibers. We estimated their stability-responsiveness tradeoff in vitro, finding two well-separated regimes. These are low-robustness regime, in which the system equilibrates quickly and responds readily to stimuli, and high-robustness regime, in which the system equilibrates slowly and is quite insensitive to stimuli. We probed the performance of both regimes in a complex environment using Fo''rster resonance energy transfer (FRET). Interestingly, the stability-responsiveness trade-off defines perfectly the extent of disassembly caused by dilution but not the one caused by protein interaction. This identifies a disconnection between intrinsic supramolecular robustness and supramolecular stability in the biological environment, strongly influenced by the disassembly pathway upon protein interaction. These findings shed light on the key features to address for supramolecular stability in the biological environment.

JTD Keywords: Azobenzene, Critical micellization, Fret, Guide, Nanoparticles, Ph, Photoisomerization, Polymerization, Shape, Water

Quandt, J, Garay-Sarmiento, M, Witzdam, L, Englert, J, Rutsch, Y, Stöcker, C, Obstals, F, Grottke, O, Rodriguez-Emmenegger, C, (2022). Interactive Hemocompatible Nanocoating to Prevent SurfaceInduced Coagulation in Medical Devices Advanced Materials Interfaces 9, 2201055

Pala, M, El Khannaji, H, Garay-Sarmiento, M, Ronda, JC, Cadiz, V, Galia, M, Percec, V, Rodriguez-Emmenegger, C, Lligadas, G, (2022). A green solvent-to-polymer upgrading approach to water-soluble LCST poly(N-substituted lactamide acrylate)s Green Chemistry 24, 8314-8323

We report a green solvent-to-polymer upgrading transformation of chemicals of the lactic acid portfolio into water-soluble lower critical solution temperature (LCST)-type acrylic polymers. Aqueous Cu(0)-mediated living radical polymerization (SET-LRP) was utilized for the rapid synthesis of N-substituted lactamide-type homo and random acrylic copolymers under mild conditions. A particularly unique aspect of this work is that the water-soluble monomers and the SET-LRP initiator used to produce the corresponding polymers were synthesized from biorenewable and non-toxic solvents, namely natural ethyl lactate and BASF's Agnique (R) AMD 3L (N,N-dimethyl lactamide, DML). The pre-disproportionation of Cu(I) Br in the presence of tris[2-(dimethylamino)ethyl]amine (Me6TREN) in water generated nascent Cu(0) and Cu(II) complexes that facilitated the fast polymerization of N-tetrahydrofurfuryl lactamide and N,N-dimethyl lactamide acrylate monomers (THFLA and DMLA, respectively) up to near-quantitative conversion with excellent control over molecular weight (5000 < M-n < 83 000) and dispersity (1.05 < D < 1.16). Interestingly, poly(THFLA) showed a degree of polymerization and concentration dependent LCST behavior, which can be fine-tuned (T-cp = 12-62 degrees C) through random copolymerization with the more hydrophilic DMLA monomer. Finally, covalent cross-linking of these polymers resulted in a new family of thermo-responsive hydrogels with excellent biocompatibility and tunable swelling and LCST transition. These illustrate the versatility of these neoteric green polymers in the preparation of smart and biocompatible soft materials.

JTD Keywords: Acid, Ethyl lactate, Living radical polymerization, Monomers, Pnipam, Reductive amination, Ruthenium nanoparticles, Set-lrp, Single, Thermoresponsive polymers

Zeinali, R, del Valle, LJ, Franco, L, Yousef, I, Rintjema, J, Aleman, C, Bravo, F, Kleij, AW, Puiggali, J, (2022). Biobased Terpene Derivatives: Stiff and Biocompatible Compounds to Tune Biodegradability and Properties of Poly(butylene succinate) Polymers 14, 161

Different copolymers incorporating terpene oxide units (e.g., limonene oxide) have been evaluated considering thermal properties, degradability, and biocompatibility. Thus, polycarbonates and polyesters derived from aromatic, monocyclic and bicyclic anhydrides have been considered. Furthermore, ring substitution with myrcene terpene has been evaluated. All polymers were amorphous when evaluated directly from synthesis. However, spherulites could be observed after the slow evaporation of diluted chloroform solutions of polylimonene carbonate, with all isopropene units possessing an R configuration. This feature was surprising considering the reported information that suggested only the racemic polymer was able to crystallize. All polymers were thermally stable and showed a dependence of the maximum degradation rate temperature (from 242 °C to 342 °C) with the type of terpene oxide. The graduation of glass transition temperatures (from 44 °C to 172 °C) was also observed, being higher than those corresponding to the unsubstituted polymers. The chain stiffness of the studied polymers hindered both hydrolytic and enzymatic degradation while a higher rate was detected when an oxidative medium was assayed (e.g., weight losses around 12% after 21 days of exposure). All samples were biocompatible according to the adhesion and proliferation tests performed with fibroblast cells. Hydrophobic and mechanically consistent films (i.e., contact angles between 90° and 110°) were obtained after the evaporation of chloroform from the solutions, having different ratios of the studied biobased polyterpenes and poly(butylene succinate) (PBS). The blend films were comparable in tensile modulus and tensile strength with the pure PBS (e.g., values of 330 MPa and 7 MPa were determined for samples incorporating 30 wt.% of poly(PA-LO), the copolyester derived from limonene oxide and phthalic anhydride. Blends were degradable, biocompatible and appropriate to produce oriented-pore and random-pore scaffolds via a thermally-induced phase separation (TIPS) method and using 1,4-dioxane as solvent. The best results were attained with the blend composed of 70 wt.% PBS and 30 wt.% poly(PA-LO). In summary, the studied biobased terpene derivatives showed promising properties to be used in a blended form for biomedical applications such as scaffolds for tissue engineering.

JTD Keywords: alternating copolymerization, biobased materials, biodegradability, composites, crystallization, cyclohexene oxide, induced phase-separation, limonene oxide, mechanical-properties, polyesters, scaffolds, spherulites, terpene derivatives, thermal properties, thermally-induced phase separation, Acetone, Bio-based, Bio-based materials, Biobased materials, Biocompatibility, Biodegradability, Butenes, Cell culture, Chlorine compounds, Degradation, Evaporation, Glass transition, Limonene oxide, Monoterpenes, Phase separation, Poly (butylenes succinate), Polybutylene succinate, Property, Ring-opening copolymerization, Scaffolds, Spheru-lites, Tensile strength, Terpene derivatives, Thermal properties, Thermally induced phase separation, Thermally-induced phase separation, Thermally?induced phase separation, Thermodynamic properties, Thermogravimetric analysis

Duro-Castano, A, Rodríguez-Arco, L, Ruiz-Pérez, L, De Pace, C, Marchello, G, Noble-Jesus, C, Battaglia, G, (2021). One-Pot Synthesis of Oxidation-Sensitive Supramolecular Gels and Vesicles Biomacromolecules 22, 5052-5064

Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization self-assembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering.

JTD Keywords: alpha-amino-acid, hydrogels, leuchs anhydrides, platform, polypeptides, transformation, triggered cargo release, Amino acids, Amphiphilics, Biocompatibility, Biodegradability, Block lengths, Controlled drug delivery, Dimethyl sulfoxide, Ethylene, Gels, Hydrophobicity, Medical nanotechnology, Methionine, Micelles, Morphology, One-pot synthesis, Organic solvents, Oxidation, Physiological condition, Polyethylene oxides, Post-polymerization, Ring-opening polymerization, Scaffolds (biology), Self assembly, Stimuli-responsive properties, Supramolecular chemistry, Supramolecular gels, Supramolecular micelles, Wormlike micelle

Maiti, B, Nandi, M, Bonardd, S, Franco, L, Puiggali, J, Enshaei, H, Aleman, C, Diaz, DD, (2021). Efficient One-Pot Preparation of Thermoresponsive Polyurethanes with Lower Critical Solution Temperatures Chempluschem 86, 1570-1576

This work reports a simple and scalable strategy to prepare a series of thermoresponsive polyurethanes synthesized via copolymerization of dicyclohexyl diisocyanate with glycerol ethoxylate in a single one-pot system. These polyurethanes exhibit lower critical solution temperatures (LCST) at 57 degrees C. The LCST of synthesized polyurethane was determined from Dynamic Scanning Calorimetry and UV-vis measurements. Both the LCST and T-g of synthesized polyurethane was tuned by varying the ratio between hard segment (dicyclohexyl diisocyanate) and soft segment (glycerol ethoxylate). Thus, T-g values could be tuned from -54.6 degrees C to -19.9 degrees C for samples with different flexibility. The swelling and deswelling studies were done at room temperature and above the LCST respectively. The results showed that the swelling ratio increases with the increase of soft segment (glycerol ethoxylate) in synthesized polyurethanes. Furthermore, the mechanical properties of the membrane were studied by universal tensile testing measurements. Specifically, stress at break values varied from 0.35 +/- 0.07 MPa to 0.91 +/- 0.15 MPa for the tested membranes, whereas elongation at break data ranged from 101.9 +/- 20.9 % to 192.4 +/- 24.4 %, and Young's modulus varied from 0.35 +/- 0.03 MPa to 1.85 +/- 0.19 MPa. Tensile strength of the films increased with the increase of the hard segment and elongation at break decreased.

JTD Keywords: copolymerization, critical solution temperatures, polyurethanes, tensile strength, Biodegradable polyurethanes, Copolymerization, Critical solution temperatures, Glycol), Polymers, Polyurethanes, Solvent-free, Tensile strength, Thermoresponsive materials

Casellas, NM, Albertazzi, L, Pujals, S, Torres, T, García-Iglesias, M, (2021). Unveiling Polymerization Mechanism in pH-regulated Supramolecular Fibers in Aqueous Media Chemistry-A European Journal 27, 11056-11060

An amine functionalized C3-symmetric benzotrithiophene (BTT) monomer has been designed and synthetized in order to form pH responsive one-dimensional supramolecular polymers in aqueous media. While most of the reported studies looked at the effect of pH on the size of the aggregates, herein, a detailed mechanistic study is reported, carried out upon modifying the pH to trigger the formation of positively charged ammonium groups. A dramatic and reversible change in the polymerization mechanism and size of the supramolecular fibers is observed and ascribed to the combination of Coulombic repulsive forces and higher monomer solubility. Furthermore, the induced frustrated growth of the fibers is further employed to finely control the one-dimensional supramolecular polymerisation and copolymerization processes.

JTD Keywords: dynamics, ph responsivity, polymerization mechanism, self-assembly, supramolecular chemistry, supramolecular polymers, Ph responsivity, Polymerization mechanism, Polymers, Self-assembly, Supramolecular chemistry, Supramolecular polymers

Saborío, M. G., Svelic, P., Casanovas, J., Ruano, G., Pérez-Madrigal, M. M., Franco, L., Torras, J., Estrany, F., Alemán, C., (2019). Hydrogels for flexible and compressible free standing cellulose supercapacitors European Polymer Journal 118, 347-357

Cellulose-based supercapacitors display important advantages in comparison with devices fabricated with other materials, regarding environmental friendliness, flexibility, cost and versatility. Recent progress in the field has been mainly focused on the utilization of cellulose fibres as: structural mechanical reinforcement of electrodes; precursors of electrically active carbon-based materials; or primary electrolytes that act as reservoirs of secondary electrolytes. In this work, a flexible, lightweight, robust, portable and manageable all-carboxymethyl cellulose symmetric supercapacitor has been obtained by assembling two electrodes based on carboxymethyl cellulose hydrogels to a solid electrolytic medium formulated with the same material. Hydrogels, which were made by cross-linking carboxymethyl cellulose paste with citric acid in water, rendered not only effective solid electrolytic media by simply loading NaCl but also electroactive electrodes. For the latter, conducting polymer microparticles, which were loaded into the hydrogel network during the physical cross-linking step, were appropriately connected through the in situ anodic polymerization of a similar conducting polymer in aqueous medium, thus creating conduction paths. The performance of the assembled supercapacitors has been proved by cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy. This design opens a new window for the green and mass production of flexible cellulose-based supercapacitors.

JTD Keywords: Conducting polymer, Energy storage, Flexible electrodes, In situ polymerization, Wearable electronics

Khurana, Kanupriya, Müller, Frank, Jacobs, Karin, Faidt, Thomas, Neurohr, Jens-Uwe, Grandthyll, Samuel, Mücklich, Frank, Canal, Cristina, Pau Ginebra, Maria, (2018). Plasma polymerized bioceramics for drug delivery: Do surface changes alter biological behaviour? European Polymer Journal 107, 25-33

One of the treatments for recurrent or complicated osteomyelitis is by local antibiotherapy mediated by suitable bone grafts. β–Tricalcium Phosphate (β–TCP) bioceramic is a resorbable bone graft. Its microporosity allows for incorporation of drugs, but a too fast release is often obtained. Complex strategies have been explored to obtain controlled drug release. In this work, plasma polymerization of a biocompatible polymer was investigated on β-TCP. Polyethyleneglycol (PEG)-like polymer coatings of different thickness were deposited on microporous β-TCP loaded with antibiotics. A highly hydrophobic surface was obtained despite the hydrophilicity of the PEG-like layer produced, which was associated to the roughness of the β-TCP substrate. The bioceramics nevertheless retained their suitable biological behavior with regard to human osteoblast cells. The microbiological activity of the antibiotics was preserved, and the coatings reduced the total amount of drug released as a function of the increasing plasma treatment time.

JTD Keywords: Plasma polymerization, β–Tricalcium phosphate, PEG-like polymer, Antibiotics, Drug release, Biocompatibility

Mir, M., Lugo, R., Tahirbegi, I. B., Samitier, J., (2014). Miniaturizable ion-selective arrays based on highly stable polymer membranes for biomedical applications Sensors 14, (7), 11844-11854

Poly(vinylchloride) (PVC) is the most common polymer matrix used in the fabrication of ion-selective electrodes (ISEs). However, the surfaces of PVC-based sensors have been reported to show membrane instability. In an attempt to overcome this limitation, here we developed two alternative methods for the preparation of highly stable and robust ion-selective sensors. These platforms are based on the selective electropolymerization of poly(3,4-ethylenedioxythiophene) (PEDOT), where the sulfur atoms contained in the polymer covalently interact with the gold electrode, also permitting controlled selective attachment on a miniaturized electrode in an array format. This platform sensor was improved with the crosslinking of the membrane compounds with poly(ethyleneglycol) diglycidyl ether (PEG), thus also increasing the biocompatibility of the sensor. The resulting ISE membranes showed faster signal stabilization of the sensor response compared with that of the PVC matrix and also better reproducibility and stability, thus making these platforms highly suitable candidates for the manufacture of robust implantable sensors.

JTD Keywords: Biomedicine, Electrochemistry, Endoscope, Implantable device, Ion-selective electrode (ISE) sensor, Ischemia, pH detection, Biocompatibility, Chemical sensors, Electrochemistry, Electrodes, Electropolymerization, Endoscopy, Functional polymers, Implants (surgical), Ion selective electrodes, Medical applications, Polyvinyl chlorides, Stabilization, Biomedical applications, Biomedicine, Implantable devices, Ion selective sensors, Ischemia, Membrane instability, pH detection, Poly(3 ,4 ethylenedioxythiophene) (PEDOT), Ion selective membranes

Hristova, K., Pecheva, E., Pramatarova, L., Altankov, G., (2011). Improved interaction of osteoblast-like cells with apatite-nanodiamond coatings depends on fibronectin Journal of Materials Science: Materials in Medicine , 22, (8), 1891-1900

New apatite (AP)/nanodiamond (ND) coating has been developed to improve physical and biological properties of stainless steel (SS) versus single AP coating. Homogeneously electrodeposited AP-ND layer demonstrates increased mechanical strength, interlayer cohesion and ductility. In the absence of serum, osteoblast-like MG63 cells attach well but poorly spread on both AP and AP-ND substrata. Pre-adsorption with serum or fibronectin (FN) improves the cellular interaction-an effect that is better pronounced on the AP-ND coating. In single protein adsorption study fluorescein isothiocyanate-labeled FN (FITC-FN) shows enhanced deposition on the AP-ND layer consistent with the significantly improved cell adhesion, spreading and focal adhesions formation (in comparison to SS and AP), particularly at low FN adsorption concentrations (1 mu g/ml). Higher FN concentrations (20 mu g/ml) abolish this difference suggesting that the promoted cellular interaction of serum (where FN is low) is caused by the greater affinity for FN. Moreover, it is found that MG63 cells tend to rearrange both adsorbed and secreted FN on the AP-ND layer suggesting facilitated FN matrix formation.

JTD Keywords: Extracellular-matrix, Protein adsorption, Integrins, Adhesion, Biomaterials, Surfaces, Polymerization, Composite, Implants, Titanium

Navarro, M., Benetti, E. M., Zapotoczny, S., Planell, J. A., Vancso, G. J., (2008). Buried, covalently attached RGD peptide motifs in poly(methacrylic acid) brush layers: The effect of brush structure on cell adhesion Langmuir 24, (19), 10996-11002

Iniferter-mediated surface-initiated photopolymerization was used to graft poly(methacrylic acid) (PMAA) brush layers obtained from surface-attached iniferters in self-assembled monolayers to a gold surface. The tethered chains were subsequently functionalized with the cell-adhesive arginine-glycine-aspartic acid (RGD) motif. The modified brushes were extended by reinitiating the polymerization to obtain an additional layer of PMAA, thereby burying the peptide-functionalized segments inside the brush structure. Contact angle measurements and Fourier transform infrared (FTIR) spectroscopy were employed to characterize the wettability and the chemical properties of these platforms. Time of flight secondary ion mass spectroscopy (TOF-SIMS) measurements were performed to monitor the chemical composition of the polymer layer as a function of the distance to the gold surface and obtain information concerning the depth of the RGD motifs inside the brush structure. The brush thickness was evaluated as a function of the polymerization (i.e.. UV-irradiation) time with atomic force microscopy (AFM) and ellipsometry. Cell adhesion tests employing human osteoblasts were performed on substrates with the RGD peptides exposed at the surface as well as covered by a PMAA top brush layer. Immunofluorescence studies demonstrated a variation of the cell morphology as a function of the position of the peptide units along the grafted chains.

JTD Keywords: Ion mass-spectrometry, Transfer radical polymerization, Asymmetric diblock copolymers, Arg-gly-asp, Swelling behaviour, Endothelial-cells, Thin-films, fibronectin, Surfaces, SIMS

Fernandez, Javier G., Mills, C. A., Martinez, E., Lopez-Bosque, M. J., Sisquella, X., Errachid, A., Samitier, J., (2008). Micro- and nanostructuring of freestanding, biodegradable, thin sheets of chitosan via soft lithography Journal of Biomedical Materials Research - Part A , 85A, (1), 242-247

A technique for imparting micro- and nano-structured topography into the surface of freestanding thin sheets of chitosan is described. Both micro- and nanometric surface structures have been produced using soft lithography. The soft lithography method, based on solvent evaporation, has allowed structures similar to 60 nm tall and similar to 500 X 500 nm(2) to be produced on freestanding similar to 0.5 mm thick sheets of the polymer when cured at 293 K, and structures similar to 400 nm tall and 5 X 5 mu m(2) to be produced when cured at 283 K. Nonstructured chitosan thin sheets (similar to 200 mu m thick) show excellent optical transmission properties in the visible portion of the electromagnetic spectrum. The structured sheets can be used for applications where optical microscopic analysis is required, such as cell interaction experiments and tissue engineering.

JTD Keywords: Chitin/chitosan, Microstructure, Nanotopography, Polymerization, Soft lithography