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1. Cationic homopolypeptides: A versatile tool to design multifunctional antimicrobial nanocoatings

Author

Leyla Kocgozlu, Angela Mutschler, Lorène Tallet, Cynthia Calligaro, Helena Knopf-Marques, Eloïse Lebaudy, Eric Mathieu, Morgane Rabineau, Varvara Gribova, Bernard Senger, N. Engin Vrana, and Philippe Lavalle

Subjects
Antibiotic substitute, Nanolayer coating, Hyaluronic acid, Antimicrobial polypeptides, Hernia mesh implants, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(l-arginine) (PAR), poly(l-lysine), and poly(l-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, in vivo investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.

Published
2024
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2. Catestatin in innate immunity and Cateslytin-derived peptides against superbugs

Author

Francesco Scavello, Angela Mutschler, Sophie Hellé, Francis Schneider, Sylvette Chasserot-Golaz, Jean-Marc Strub, Sarah Cianferani, Youssef Haikel, and Marie-Hélène Metz-Boutigue

Subjects
Medicine, Science
Abstract

Abstract Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus. In addition to Cateslytin (Ctl, bovine CgA344-358), the active domain of Catestatin, several peptides including dimers, D-isomer and the new designed peptide DOPA-K-DOPA-K-DOPA-TLRGGE-RSMRLSFRARGYGFR (Dopa5T-Ctl) were prepared and tested. Cateslytin is resistant to bacterial degradation and does not induce bacterial resistance. The interaction of Catestatin with immune dermal cells (dendritic cells DC1a, dermal macrophages CD14 and macrophages) was analyzed by using confocal microscopy and cytokine release assay. The dimers and D-isomer of Ctl were tested against a large variety of bacteria showing the potent antibacterial activity of the D-isomer. The peptide Dopa5T-Ctl is able to induce the self-killing of S. aureus after release of Ctl by the endoprotease Glu-C produced by this pathogen. It permits localized on-demand delivery of the antimicrobial drug directly at the infectious site.

Published
2021
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3. The Catestatin-Derived Peptides Are New Actors to Fight the Development of Oral Candidosis

Author

Davide Mancino, Naji Kharouf, Francesco Scavello, Sophie Hellé, Fouad Salloum-Yared, Angela Mutschler, Eric Mathieu, Philippe Lavalle, Marie-Hélène Metz-Boutigue, and Youssef Haïkel

Subjects
candidosis, resistance, antifungal, antimicrobial peptides, Catestatin, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Resistance to antifungal therapy of Candida albicans and non-albicans Candida strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against Candida species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of C. albicans, C. tropicalis and C. glabrata was the D-isomer of Cateslytin (D-bCtl) whereas the efficiency of the L-isomer (L-bCtl) significantly decreases against C. glabrata strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the L-bCtl and D-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the L- isomer of Catestatin (L-bCts) had a synergistic effect against Candida albicans especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with L-bCtl, suggesting the importance of the C-terminal end of L-bCts (GPGLQL) for the interaction with BSA. In this context in vitro D-bCtl, as well as the combination of BSA with L-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to Candida and non-Candida albicans, without detrimental side effects.

Published
2022
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5. Theoretical and Experimental Elucidation of the Adsorption Process of a Bioinspired Peptide on Mineral Surfaces

Author

Angela Mutschler, Lorène Tallet, J. Touzeau, François Maurel, Mahamadou Seydou, Florent Barbault, and Ph. Lavalle

Subjects
chemistry.chemical_classification, Surface Properties, Peptidomimetic, Proteins, Peptide, Surfaces and Interfaces, Adhesion, Polymer, Silicon Dioxide, Condensed Matter Physics, Electrostatics, Atomic units, Redox, Adsorption, Chemical engineering, chemistry, Electrochemistry, General Materials Science, Gold, Peptides, Spectroscopy
Abstract

Inorganic materials used for biomedical applications such as implants generally induce the adsorption of proteins on their surface. To control this phenomenon, the bioinspired peptidomimetic polymer 1 (PMP1), which aims to reproduce the adhesion of mussel foot proteins, is commonly used to graft specific proteins on various surfaces and to regulate the interfacial mechanism. To date and despite its wide application, the elucidation at the atomic scale of the PMP1 mechanism of adsorption on surfaces is still unknown. The purpose of the present work was thus to unravel this process through experimental and computational investigations of adsorption of PMP1 on gold, TiO2, and SiO2 surfaces. A common mechanism of adsorption is identified for the adsorption of PMP1 which emphasizes the role of electrostatics to approach the peptide onto the surface followed by a full adhesion process where the entropic desolvation step plays a key role. Besides, according to the fact that mussel naturally controls the oxidation states of its proteins, further investigations were performed for two distinct redox states of PMP1, and we conclude that even if both states are able to allow interaction of PMP1 with the surfaces, the oxidation of PMP1 leads to a stronger interaction.

Published
2021

6. Assembly of Fluorescent Polymer Nanoparticles Using Different Microfluidic Mixers

Author

Huaiyou Chen, Ali Emre Celik, Angela Mutschler, Antoine Combes, Anne Runser, Andrey S. Klymchenko, Sébastien Lecommandoux, Christophe A. Serra, Andreas Reisch, Admin, Oskar, Université de Strasbourg (UNISTRA), Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Polymères Organiques (LCPO), Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Team 3 LCPO : Polymer Self-Assembly & Life Sciences, Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[CHIM.POLY] Chemical Sciences/Polymers, Polymers, Microfluidics, Surfaces and Interfaces, Fluorescent nanoparticles, Condensed Matter Physics, Drug Delivery Systems, Polymer nanoparticles, Size control, [CHIM.POLY]Chemical Sciences/Polymers, Electrochemistry, Nanoparticles, General Materials Science, Particle Size, Nanoprecipitation, Spectroscopy, Fluorescent Dyes
Abstract

Nanoprecipitation is a facile and efficient approach to the assembly of loaded polymer nanoparticles (NPs) for applications in bioimaging and targeted drug delivery. Their successful use in clinics requires reproducible and scalable synthesis, for which microfluidics appears as an attractive technique. However, in the case of nanoprecipitation, particle formation depends strongly on mixing. Here, we compare 5 different types of microfluidic mixers with respect to the formation and properties of poly(d-l-lactide--glycolide) (PLGA) and poly(methyl methacrylate) NPs loaded with a fluorescent dye salt: a cross-shaped mixer, a multilamination mixer, a split and recombine mixer, two herringbone mixers, and two impact jet mixers. Size and fluorescence properties of the NPs obtained with these mixers are evaluated. All mixers, except the cross-shaped one, yield NPs at least as small and fluorescent as those obtained manually. Notably in the case of impact jet mixers operated at high flow speeds, the size of the NPs could be strongly reduced from >50 nm down to 70%. These results show the importance of precisely controlling the assembly conditions for loaded polymer NPs. The present work further provides guidance for choosing the optimal microfluidic setup for production of nanomaterials for biomedical applications.

Published
2022

7. Large Hybrid Polymer/Lipid Unilamellar Vesicle (LHUV) at the nanoscale: An insight into the lipid distribution in the membrane and permeability control

Author

Annie Brûlet, Martin Fauquignon, Elise Courtecuisse, Jean-François Le Meins, Angela Mutschler, Marc Schmutz, Romane Josselin, Laboratoire de Chimie des Polymères Organiques (LCPO), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Team 3 LCPO : Polymer Self-Assembly & Life Sciences, Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Laboratoire Léon Brillouin (LLB - UMR 12), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Groupe Diffusion petits angles (GDPA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, LLB - Matière molle et biophysique (MMB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Admin, Oskar

Subjects
Polymersomes, [CHIM.POLY] Chemical Sciences/Polymers, Materials science, Membrane permeability, Polymers, Lipid Bilayers, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Nanoreactor, Permeability, Polyethylene Glycols, Membrane Permeability, Biomaterials, chemistry.chemical_compound, Colloid and Surface Chemistry, Small Angle Neutron Scattering (SANS), POPC, Unilamellar Liposomes, Liposome, Molar mass, Vesicle, Membrane structure, technology, industry, and agriculture, Cryo Transmission Electron Microscopy (Cryo-TEM), 021001 nanoscience & nanotechnology, [PHYS.COND.CM-SCM] Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Molecular Weight, Membrane, [CHIM.POLY]Chemical Sciences/Polymers, Chemical engineering, chemistry, Hybrid Polymer/Lipid Vesicle, Polymersome, Liposomes, lipids (amino acids, peptides, and proteins), 0210 nano-technology, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]
Abstract

Membrane structuration of Large Hybrid Unilamellar Polymer/Lipid Vesicle (LHUV) is an important parameter on the optimization of their properties and thus their valuation in various fields. However, this kind of information is hardly accessible. In this work, we will focus on the development of LHUV obtained from the self-assembly of diblock poly(dimethylsiloxane)-b-poly(ethylene oxide) (PDMS-b-PEO) of different molar masses combined with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at 15% and 25% w/w content. The hybrid character of the resulting vesicles as well as their membrane structure are characterized by the mean of different techniques such as small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). We show that hybrid vesicles with homogeneous membrane structure are obtained whatever the molar mass of the block copolymer (from 2500 to 4000 g/mol), with of a small number of tubular structures observed with the higher molar mass. We also demonstrate that the permeability of the LHUV, evaluated through controlled release experiments of fluorescein loaded in LHUV, is essentially controlled by the lipid/polymer composition.

Published
2021

8. Catestatin in innate immunity and Cateslytin-derived peptides against superbugs

Author

Jean-Marc Strub, Sophie Hellé, Francis Schneider, Sylvette Chasserot-Golaz, Marie-Hélène Metz-Boutigue, Angela Mutschler, Francesco Scavello, Youssef Haikel, Sarah Cianférani, Gaillard, Brigitte, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and BioMaterials and BioEngeneering - INSERM - UMR_S 1121

Subjects
0301 basic medicine, Staphylococcus aureus, Science, CD14, [SDV]Life Sciences [q-bio], Antimicrobial peptides, Diseases, Peptide, medicine.disease_cause, Biochemistry, Microbiology, Article, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Immune system, Anti-Infective Agents, [CHIM] Chemical Sciences, medicine, Animals, Humans, [CHIM]Chemical Sciences, chemistry.chemical_classification, Multidisciplinary, Innate immune system, Antimicrobial, Immunity, Innate, 3. Good health, [SDV] Life Sciences [q-bio], CTL, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Medicine, Cattle, Peptides
Abstract

Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus. In addition to Cateslytin (Ctl, bovine CgA344-358), the active domain of Catestatin, several peptides including dimers, D-isomer and the new designed peptide DOPA-K-DOPA-K-DOPA-TLRGGE-RSMRLSFRARGYGFR (Dopa5T-Ctl) were prepared and tested. Cateslytin is resistant to bacterial degradation and does not induce bacterial resistance. The interaction of Catestatin with immune dermal cells (dendritic cells DC1a, dermal macrophages CD14 and macrophages) was analyzed by using confocal microscopy and cytokine release assay. The dimers and D-isomer of Ctl were tested against a large variety of bacteria showing the potent antibacterial activity of the D-isomer. The peptide Dopa5T-Ctl is able to induce the self-killing of S. aureus after release of Ctl by the endoprotease Glu-C produced by this pathogen. It permits localized on-demand delivery of the antimicrobial drug directly at the infectious site.

Published
2021

9. Multifunctional polymeric implant coatings based on gelatin, hyaluronic acid derivative and chain length-controlled poly(arginine)

Author

Florent Dufour, Christophe A. Marquette, Morgane Rabineau, Sarah Lachaal, Nihal Engin Vrana, Edwin-Joffrey Courtial, Philippe Lavalle, Helena Knopf-Marques, Céline Muller, Julie Bystroňová, Angela Mutschler, Julien Barthes, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Protip Medical [Strasbourg], Laboratoire de Chimie des Polymères Organiques (LCPO), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Team 3 LCPO : Polymer Self-Assembly & Life Sciences, Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Faculté de chirurgie dentaire - Strasbourg, Université de Strasbourg (UNISTRA), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Contipro, Contipro Biotech S. R. O, and Protip medical

Subjects
Vascular Endothelial Growth Factor A, food.ingredient, Materials science, Arginine, Polymers, Bioengineering, 02 engineering and technology, engineering.material, 010402 general chemistry, 01 natural sciences, Gelatin, Biomaterials, Extracellular matrix, chemistry.chemical_compound, food, Coated Materials, Biocompatible, Coating, Hyaluronic acid, Human Umbilical Vein Endothelial Cells, Animals, Humans, Secretion, Hyaluronic Acid, ComputingMilieux_MISCELLANEOUS, Prostheses and Implants, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Antimicrobial, Anti-Bacterial Agents, Extracellular Matrix, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Mechanics of Materials, Biophysics, engineering, Cattle, Implant, Peptides, 0210 nano-technology
Abstract

Surface of the implantable devices is the root cause of several complications such as infections, implant loosening and chronic inflammation. There is an urgent need for multifunctional coatings that can address these shortcomings simultaneously in a manner similar to the structures of extracellular matrix. Herein, we developed a coating system composed of ECM components and a naturally derived polypeptide. The interactions between the coating components create an environment that enables incorporation of an antimicrobial/angiogenic polypeptide. The film composition is based gelatin and hyaluronic acid modified with aldehyde groups (HA-Ald) that can react with poly (arginine) (PAR) through transient interactions. Nanoplasmon measurements demonstrated a significantly higher loading of PAR in films containing HA-Ald with longer retention of PAR in the structure. The presence of PAR not only provides to the film surface antimicrobial (contact-killing) properties but also increased endothelial cell-cell contacts (PECAM) and VEGFA gene expression and secretion by human vascular endothelial cells. This multifunctional coating can be easily applied to surface of implants where it can enact on several problems simultaneously.

Published
2019

10. On the Infectivity of Bacteriophages in Polyelectrolyte Multilayer Films: Inhibition or Preservation of Their Bacteriolytic Activity?

Author

Romain Rivet, Ozge Erdemli, Céline Caillet, Christophe Gantzer, Angela Mutschler, Balla Doucouré, Jérôme F. L. Duval, Grégory Francius, Philippe Lavalle, Jalal Bacharouche, Institut de Science des Matériaux de Mulhouse (IS2M), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Faculté de chirurgie dentaire - Strasbourg, Université de Strasbourg (UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace, and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)

Subjects
Infectivity, Materials science, Swelling ratio, Atomic force microscopy, Polymers, Biocompatible Materials, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, Microscopy, Atomic Force, 01 natural sciences, Polyelectrolytes, Polyelectrolyte, Dynamic Light Scattering, 0104 chemical sciences, Chemical engineering, Dynamic light scattering, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [CHIM]Chemical Sciences, General Materials Science, Bacteriophages, Biological Assay, 0210 nano-technology, Selectivity, ComputingMilieux_MISCELLANEOUS
Abstract

Antibiotic resistance in bacterial cells has motivated the scientific community to design new and efficient (bio)materials with targeted bacteriostatic and/or bactericide properties. In this work, a series of polyelectrolyte multilayer films differing in terms of polycation-polyanion combinations are constructed according to the layer-by-layer deposition method. Their capacities to host T4 and φx174 phage particles and maintain their infectivity and bacteriolytic activity are thoroughly examined. It is found that the macroscopic physicochemical properties of the films, which includes film thickness, swelling ratio, or mechanical stiffness (as derived by atomic force microscopy and spectroscopy measurements), do not predominantly control the selectivity of the films for hosting infective phages. Instead, it is evidenced that the intimate electrostatic interactions locally operational between the loaded phages and the polycationic and polyanionic PEM components may lead to phage activity reduction and preservation/enhancement, respectively. It is argued that the underlying mechanism involves the screening of the phage capsid receptors (operational in cell recognition/infection processes) because of the formation of either polymer-phage hetero-assemblies or polymer coating surrounding the bioactive phage surface.

Published
2018

11. Alginate/Chitosan Compact Polyelectrolyte Complexes: A Cell and Bacterial Repellent Material

Author

Fouzia Boulmedais, Béatrice Heurtault, Thida Phoeung, Benoît Frisch, Joseph Hemmerlé, Fabienne Perrin-Schmitt, Dominique Collin, Sylvie Fournel, Michel Rawiso, Andreas Reisch, Philippe Lavalle, Maria Vittoria Spanedda, Emilie Roger, Pierre Schaaf, Angela Mutschler, Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hormonologie, Les Hôpitaux Universitaires de Strasbourg (HUS), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Mutschler, Angela, Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), U1121, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[CHIM.POLY] Chemical Sciences/Polymers, Materials science, General Chemical Engineering, Modulus, Salt (chemistry), Alginate chitosan, 02 engineering and technology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010402 general chemistry, Polysaccharide, 01 natural sciences, Chitosan, chemistry.chemical_compound, Polymer chemistry, Materials Chemistry, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, [CHIM.MATE] Chemical Sciences/Material chemistry, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Polyelectrolyte, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, Chemical engineering, chemistry, Homogeneous, Ultracentrifuge, 0210 nano-technology
Abstract

Ultracentrifugated compact polyelectrolyte complexes (uCoPECs) represent a new class of materials that are obtained by ultracentrifugation of solutions of polyanion/polycation complexes in the presence of salt. In the present study, two polysaccharides, chitosan and alginate, were used to form such complexes, thus providing a solid material uniquely composed of polysaccharides. The conditions for obtaining the uCoPEC material were optimized: the optimal salt concentration and polysaccharide concentrations were assessed, and the ultracentrifugation speed proved to be a key parameter to obtain compact and homogeneous materials. The Young's modulus, E, of the material was of the order of 12 MPa, which is the highest E value measured for a uCoPEC. The material contained nanometer-sized crystals of chitosan as indicated by X-ray diffraction. Most strikingly, this material proves to be totally cell- and bacteria-resistant. Immunological tests show that this uCoPEC does not induce any proinflammatory response. T...

Published
2017

12. Nature of the Polyanion Governs the Antimicrobial Properties of Poly(arginine)/Polyanion Multilayer Films

Author

Cosette Betscha, Pierre Schaaf, Fouzia Boulmedais, Bernard Senger, Angela Mutschler, Vincent Ball, André P. Schroder, Nihal Engin Vrana, Philippe Lavalle, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), ProtipMedical [Strasbourg], Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mutschler, Angela, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
chemistry.chemical_classification, Isothermal microcalorimetry, [CHIM.POLY] Chemical Sciences/Polymers, [CHIM.MATE] Chemical Sciences/Material chemistry, Poly arginine, Materials science, Arginine, General Chemical Engineering, Diffusion, technology, industry, and agriculture, 02 engineering and technology, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, Antimicrobial, Polysaccharide, 01 natural sciences, Polyelectrolyte, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Polymer chemistry, Materials Chemistry, 0210 nano-technology
Abstract

International audience; Coatings with antimicrobial properties are garnering interest to prevent implant-associated infections. Recently, we showed that poly(arginine)/hyaluronic acid (PAR/HA) multilayers built with PAR chains constituted from 30 arginine residues (PAR30) have strong antimicrobial properties through a contact-killing mechanism. This property is due to the ability of PAR30 chains, when associated with HA, to diffuse in the multilayer. Here, we investigate the effect of the nature of the polyanion on the antimicrobial activity of (PAR30/polyanion) multilayers. Four polysaccharides, one polypeptide, and one synthetic polyelectrolyte are investigated. Surprisingly, only HA leads to films with antimicrobial character. We relate this property to the strong diffusion capacity of PAR30 chains in (PAR30/HA) multilayers compared to their diffusion ability in the other (PAR30/polyanion) films. Through isothermal microcalorimetry experiments, we also demonstrate that interactions in solutions of PAR30 chains with the different polyanions are characterized by a negative reaction enthalpy for all of the investigated polyanions except for HA, where the enthalpy of reaction is positive. Moreover, the molecular weight of HA is not a key parameter for the diffusion ability of PAR chains or for the bioactivity of the film. These results constitute an important step toward the establishment of rules to design contact-killing antimicrobial polyelectrolyte multilayers

Published
2017

13. Establishing contact between cell-laden hydrogels and metallic implants with a biomimetic adhesive for cell therapy supported implants

Author

Garrett B. McGuinness, Camille Dollinger, Guillaume Gaudinat, Philippe Lavalle, Angela Mutschler, Vincent Le Houérou, Nihal Engin Vrana, Julien Barthes, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Protip Medical [Strasbourg], LAboratoire de Recherche en Mécanique Appliquée (LARMAUR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), 602694, European Union’s Seventh Framework Programme for research, technological development and demonstration, Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
food.ingredient, Materials science, Biomedical Engineering, Biocompatible Materials, Bioengineering, 02 engineering and technology, engineering.material, Prosthesis Design, 010402 general chemistry, complex mixtures, 01 natural sciences, Gelatin, Biomaterials, Mice, food, Coating, Biomimetic Materials, Adhesives, Cell Adhesion, Animals, Humans, Composite material, Cell adhesion, ComputingMilieux_MISCELLANEOUS, Transglutaminases, Lysine, Quinones, Implant failure, Hydrogels, [CHIM.MATE]Chemical Sciences/Material chemistry, 3T3 Cells, Prostheses and Implants, Adhesion, Fibroblasts, Hydrogen-Ion Concentration, 021001 nanoscience & nanotechnology, Bivalvia, Dihydroxyphenylalanine, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Metals, Self-healing hydrogels, engineering, Implant, Adhesive, Peptides, 0210 nano-technology, Biomedical engineering
Abstract

For in-dwelling implants, controlling the biological interface is a crucial parameter to promote tissue integration and prevent implant failure. For this purpose, one possibility is to facilitate the establishment of the interface with cell-laden hydrogels fixed to the implant. However, for proper functioning, the stability of the hydrogel on the implant should be ensured. Modification of implant surfaces with an adhesive represents a promising strategy to promote the adhesion of a cell-laden hydrogel on an implant. Herein, we developed a peptidic adhesive based on mussel foot protein (L-DOPA-L-lysine)2-L-DOPA that can be applied directly on the surface of an implant. At physiological pH, unoxidized (L-DOPA-L-lysine)2-L-DOPA was supposed to strongly adhere to metallic surfaces but it only formed a very thin coating (less than 1 nm). Once oxidized at physiological pH, (L-DOPA-L-lysine)2-L-DOPA forms an adhesive coating about 20 nm thick. In oxidized conditions, L-lysine can adhere to metallic substrates via electrostatic interaction. Oxidized L-DOPA allows the formation of a coating through self-polymerization and can react with amines so that this adhesive can be used to fix extra-cellular matrix based materials on implant surfaces through the reaction of quinones with amino groups. Hence, a stable interface between a soft gelatin hydrogel and metallic surfaces was achieved and the strength of adhesion was investigated. We have shown that the adhesive is non-cytotoxic to encapsulated cells and enabled the adhesion of gelatin soft hydrogels for 21 days on metallic substrates in liquid conditions. The adhesion properties of this anchoring peptide was quantified by a 180° peeling test with a more than 60% increase in peel strength in the presence of the adhesive. We demonstrated that by using a biomimetic adhesive, for the application of cell-laden hydrogels to metallic implant surfaces, the hydrogel/implant interface can be ensured without relying on the properties of the deposited biomaterials.

Published
2017

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