Low-grade chronic inflammation underlies the development of the most dangerous cardiometabolic disorders including type 2 diabetes and its vascular complications. In contrast to acute inflammation induced by bacteria and viruses, chronic inflammation can be driven by abnormal reaction to endogenous factors, including Th2 cytokines, metabolic factors like advanced glycation end products (AGEs), modified lipoproteins, or hyperglycemia. The key innate immune cells that recognize these factors in blood circulation are monocytes. Inflammatory programming of monocytes which migrate into tissues can, in turn, result into generation of tissue macrophages with pathological functions. Therefore, determination of the molecular and functional phenotype of circulating monocytes is a very promising diagnostic tool for the identification of hidden inflammation, which can precede the development of the pathology. Here we propose a new test system for the identification of inflammatory programming of monocytes: surface biomarkers and ex vivo functional system. We summarize the current knowledge about surface biomarkers for monocyte subsets, including CD16, CCR2, CX3CR1, CD64, stabilin-1 and CD36, and their association with inflammatory human disorders. Furthermore, we present the design of an ex vivo monocyte-based test system with minimal set of parameters as a potential diagnostic tool for the identification of personalized inflammatory responses.
Event Abstract Back to Event Harnessing the multifunctionality in nature: a bioactive agent release system with self-antimicrobial and immunomodulatory properties Hayriye Ozcelik1, Engin Vrana1, 2, Alexandru Gudima3, Julia Kzhyshkowska3, Pierre Schaaf1 and Philippe Lavalle1 1 INSERM, Unit 1121 Biomaterials and Bioengineering, France 2 Protip Medical, France 3 Heidelberg University, Institute of Transfusion Medicine and Immunology, Germany All implantable biomedical systems face several risks once in contact with the host tissue. The main problems are i) excessive immune response to the implant; ii) development of bacterial biofilms and iii) yeast and fungi infections. A multifunctional surface coating which can address all these issues concomitantly would significantly improve clinical outcomes. We develop here for the first time a multifunctional coating that allows addressing these three issues simultaneously. We hypothesized that polyarginine (PAR), a synthetic highly cationic polypeptide, can act on macrophages to control innate immune response because arginine is an important component of macrophage metabolism. Moreover, PAR is susceptible to act as an antimicrobial agent due to its positive charges. In order to exploit these properties we developed a new polyelectrolyte multilayer (PEM) films based on PAR and hyaluronic acid (HA), which is a compound also known as an immunomodulator. It is first shown that this multilayer presents a thickness that increases exponentially as a function of the number of deposition steps. The PAR/HA films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophages subpopulations. This could reduce potential chronic inflammatory reaction following implantation. Next, we show that PAR has an antimicrobial activity both in solution and in film format. PAR/HA films were very effective against S. aureus for 24 h. In order to have a long-term antimicrobial activity, we tested deposition of a precursor nanoscale silver coating on the surface before adding the PAR/HA films. A synergistic effect due to the simultaneous presence of PAR/HA and silver coating was observed, enhancing both the short-term antimicrobial activity and conferring a longterm effect. The PAR/HA films can be easily further functionalized by embedding antimicrobial peptides, like catestatin (CAT), a natural host defense peptide. This PAR/HA+CAT film proved to be effective as an antimicrobial coating against yeast and fungi. The cytocompatibility of the PAR/HA films was assessed with human umbilical vein endothelial cells (HUVECs). This all-in-one system that limit strong inflammation and prevent bacteria, yeast and fungi infections constitutes an original strategy to coat implants in an active way, especially the implants located in nonsterile environments such as dental, pharyngeal or tracheal implants. Materials Institute Carnot Alsace (MICA), MicroSurf project; European Union FP7, IMMODGEL project No: 602694References:[1] H. Ozcelik, N. E. Vrana, A. Gudima, V. Riabov, A. Gratchev, Y. Haikel, M.-H. Metz-Boutigue, A. Carrad`o, J. Faerber, T. Roland,H. Kl¨uter, J. Kzhyshkowska, P. Schaaf, P. Lavalle, Harnessing the Multifunctionality in Nature: A Bioactive Agent Release System with Self-Antimicrobial and Immunomodulatory Properties, Advanced Healthcare Materials, in press. Keywords: Infection, self-assembly, biofunctionalization, Polypeptide Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Anti-infective biomaterials Citation: Ozcelik H, Vrana E, Gudima A, Kzhyshkowska J, Schaaf P and Lavalle P (2016). Harnessing the multifunctionality in nature: a bioactive agent release system with self-antimicrobial and immunomodulatory properties. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00833 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hayriye Ozcelik Engin Vrana Alexandru Gudima Julia Kzhyshkowska Pierre Schaaf Philippe Lavalle Google Hayriye Ozcelik Engin Vrana Alexandru Gudima Julia Kzhyshkowska Pierre Schaaf Philippe Lavalle Google Scholar Hayriye Ozcelik Engin Vrana Alexandru Gudima Julia Kzhyshkowska Pierre Schaaf Philippe Lavalle PubMed Hayriye Ozcelik Engin Vrana Alexandru Gudima Julia Kzhyshkowska Pierre Schaaf Philippe Lavalle Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.
A1 Predictive and prognostic biomarker panel for targeted application of radioembolisation improving individual outcomes in hepatocellular carcinoma Jella-Andrea Abraham, Olga Golubnitschaja A2 Integrated market access approach amplifying value of “Rx-CDx” Ildar Akhmetov A3 Disaster response: an opportunity to improve global healthcare Russell J. Andrews, Leonidas Quintana A4 USA PPPM: proscriptive, profligate, profiteering medicine-good for 1 % wealthy, not for 99 % unhealthy Russell J. Andrews A5 The role of IDO in a murine model of gingivitis: predictive and therapeutic potentials Babak Baban, Jun Yao Liu, Xu Qin, Tailing Wang, Mahmood S. Mozaffari A6 Specific diets for personalised treatment of diabetes type 2 Viktoriia V. Bati, Tamara V. Meleshko, Olga B. Levchuk, Nadiya V. Boyko A7 Towards personalized physiotherapeutic approach Joanna Bauer, Ewa Boerner, Halina Podbielska A8 Cells, animal, SHIME and in silico models for detection and verification of specific biomarkers of non-communicable chronic diseases Alojz Bomba, Viktor O. Petrov, Volodymyr G. Drobnych, Rostyslav V. Bubnov, Oksana M. Bykova, Nadiya V. Boyko A9 INTERACT-chronic care model: Self-treatment by patients with decision support e-Health solution Hans-Peter Brunner-La Rocca, Lutz Fleischhacker, Olga Golubnitschaja, Frank Heemskerk, Thomas Helms, Tiny Jaarsma, Judita Kinkorova, Jan Ramaekers, Peter Ruff, Ivana Schnur, Emilio Vanoli, Jose Verdu A10 PPPM in cardiovascular medicine in 2015 Hans-Peter Brunner-La Rocca A11 Magnetic resonance imaging of nanoparticles in mice, potential for theranostic and contrast media development – pilot results Rostyslav V. Bubnov, Sergiy A. Grabovetskyi, Olena M. Mykhalchenko, Natalia O. Tymoshok, Oleksandr B. Shcherbakov, Igor P. Semeniv, Mykola Y. Spivak A12 Ultrasound diagnosis for diabetic neuropathy - comparative study Rostyslav V. Bubnov, Tetyana V. Ostapenko A13 Ultrasound for stratification patients with diabetic foot ulcers for prevention and personalized treatment - pilot results Rostyslav V. Bubnov, Nazarii M. Kobyliak, Nadiya M. Zholobak, Mykola Ya. Spivak A14 Project ImaGenX – designing and executing a questionnaire on environment and lifestyle risk of breast cancer John Paul Cauchi A15 Genomics – a new structural brand of predictive, preventive and personalized medicine or the new driver as well? Dmitrii Cherepakhin, Marina Bakay, Artem Borovikov, Sergey Suchkov A16 Survey of questionnaires for evaluation of the quality of life in various medical fields Barbara Cieślik, Agnieszka Migasiewicz, Maria-Luiza Podbielska, Markus Pelleter, Agnieszka Giemza, Halina Podbielska A17 Personalized molecular treatment for muscular dystrophies Sebahattin Cirak A18 Secondary mutations in circulating tumour DNA for acquired drug resistance in patients with advanced ALK + NSCLC Marzia Del Re, Paola Bordi, Valentina Citi, Marta Palombi, Carmine Pinto, Marcello Tiseo, Romano Danesi A19 Recombinant species-specific FcεRI alpha proteins for diagnosis of IgE-mediated allergies in dogs, cats and horses Lukas Einhorn, Judit Fazekas, Martina Muhr, Alexandra Schoos, Lucia Panakova, Ina Herrmann, Krisztina Manzano-Szalai, Kumiko Oida, Edda Fiebiger, Josef Singer, Erika Jensen-Jarolim A20 Global methodology for developmental neurotoxicity testing in humans and animals early and chronically exposed to chemical contaminants Arpiné A. Elnar, Nadia Ouamara, Nadiya Boyko, Xavier Coumoul, Jean-Philippe Antignac, Bruno Le Bizec, Gauthier Eppe, Jenny Renaut, Torsten Bonn, Cédric Guignard, Margherita Ferrante, Maria Liusa Chiusano, Salvatore Cuzzocrea, Gerard O'Keeffe, John Cryan, Michelle Bisson, Amina Barakat, Ihsane Hmamouchi, Nasser Zawia, Anumantha Kanthasamy, Glen E. Kisby, Rui Alves, Oscar Villacañas Pérez, Kim Burgard, Peter Spencer, Norbert Bomba, Martin Haranta, Nina Zaitseva, Irina May, Stéphanie Grojean, Mathilde Body-Malapel, Florencia Harari, Raul Harari, Kristina Yeghiazaryan, Olga Golubnitschaja, Vittorio Calabrese, Christophe Nemos, Rachid Soulimani A21 Mental indicators at young people with attributes hypertension and pre-hypertension Maria E. Evsevyeva, Elena A. Mishenko, Zurida V. Kumukova, Evgeniy V. Chudnovsky, Tatyana A. Smirnova A22 On the approaches to the early diagnosis of stress-induced hypertension in young employees of State law enforcement agencies Maria E. Evsevyeva, Ludmila V. Ivanova, Michail V. Eremin, Maria V. Rostovtseva A23 Сentral aortic pressure and indexes of augmentation in young persons in view of risk factors Maria E. Evsevyeva, Michail V. Eremin, Vladimir I. Koshel, Oksana V. Sergeeva, Nadesgda M. Konovalova A24 Breast cancer prediction and prevention: Are reliable biomarkers in horizon? Shantanu Girotra, Olga Golubnitschaja A25 Flammer Syndrome and potential formation of pre-metastatic niches: A multi-centred study on phenotyping, patient stratification, prediction and potential prevention of aggressive breast cancer and metastatic disease Olga Golubnitschaja, Manuel Debald, Walther Kuhn, Kristina Yeghiazaryan, Rostyslav V. Bubnov, Vadym M. Goncharenko, Ulyana Lushchyk, Godfrey Grech, Katarzyna Konieczka A26 Innovative tools for prenatal diagnostics and monitoring: improving individual pregnancy outcomes and health-economy in EU Olga Golubnitschaja, Jan Jaap Erwich, Vincenzo Costigliola, Kristina Yeghiazaryan, Ulrich Gembruch A27 Immunohistochemical assessment of APUD cells in endometriosis Vadym M. Goncharenko, Vasyl O. Beniuk, Olga V. Kalenska, Rostyslav V. Bubnov A28 Updating personalized management algorithm of endometrial hyperplasia in pre-menopause women Vadym M. Goncharenko, Vasyl O. Beniuk, Rostyslav V. Bubnov, Olga Melnychuk A29 The personified treatment approach of polimorbid patients with periodontal inflammatory diseases Irina A. Gorbacheva, Lyudmila Y. Orekhova, Vadim V. Tachalov A30 Ukrainian experience in hybrid war – the challenge to update algorithms for personalized care and early prevention of different military injuries Olena I. Grechanyk, Rizvan Ya. Abdullaiev, Rostyslav V. Bubnov A31 Tear fluid biomarkers: a comparison of tear fluid sampling and storage protocols Suzanne Hagan, Eilidh Martin, Ian Pearce, Katherine Oliver A32 The correlation of dietary habits with gingival problems during menstruation Cenk Haytac, Fariz Salimov, Servin Yoksul, Anatoly A. Kunin, Natalia S. Moiseeva A33 Genomic medicine in a contemporary Spanish population of prostate cancer: our experience Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, Antonia Angulo, Francisco Javier Machuca Santa-Cruz A34 Challenges, opportunities and collaborations for personalized medicine applicability in uro-oncological disease Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara A35 Metabolic hallmarks of cancer as targets for a personalized therapy John Ionescu A36 Influence of genetic polymorphism as a predictor of the development of periodontal disease in patients with gastric ulcer and 12 duodenal ulcer Alfiya Z. Isamulaeva, Anatoly A. Kunin, Shamil Sh. Magomedov, Aida I. Isamulaeva A37 Challenges in diabetic macular edema Tatjana Josifova A38 Overview of the EPMA strategies in laboratory medicine relevant for PPPM Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, Vincenzo Costigliola A39 EPMA initiative for effective organization of medical travel: European concepts and criteria Vincenzo Costigliola, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja A40 Design and innovation in e-textiles: implications for PPPM Anthony Kent, Tom Fisher, Tilak Dias A41 Biobank in Pilsen as a member of national node BBMRI_CZ Judita Kinkorová, Ondřej Topolčan A42 Big data in personalized medicine: hype and hope Matthias Kohl A43 The 3P approach as the platform of the European Dentistry Department (DPPPD) Anatoly A. Kunin, Natalia S. Moiseeva A44 The endometrium cytokine patterns for predictive diagnosis of proliferation severity and cancer prevention Andrii I. Kurchenko, Vasyl A. Beniuk, Vadym M. Goncharenko, Rostyslav V. Bubnov, Nadiya V. Boyko, Andriy M. Strokan A45 A monocyte-based in-vitro system for testing individual responses to the implanted material: future for personalized implant construction Julia Kzhyshkowska, Alexandru Gudima, Ksenia S. Stankevich, Victor D. Filimonov4, Harald Klüter, Evgeniya M. Mamontova, Sergei I. Tverdokhlebov A46 Prediction and prevention of adverse health effects by meteorological factors: Biomarker patterns and creation of a device for self-monitoring and integrated care Ulyana B. Lushchyk, Viktor V. Novytskyy, Igor P. Babii, Nadiya G. Lushchyk, Lyudmyla S. Riabets, Ivanna I. Legka A47 Targeting "disease signatures" towards personalized healthcare Mira Marcus-Kalish, Alexis Mitelpunkt, Tal Galili, Neta Shachar, Yoav Benjamini A48 Influence of the skin imperfection on the personal quality of life and possible tools for objective diagnosis Agnieszka Migasiewicz, Markus Pelleter, Joanna Bauer, Ewelina Dereń, Halina Podbielska A49 The new direction in caries prevention based on the ultrastructure of dental hard tissues and filling materials Natalia S. Moiseeva, Anatoly A. Kunin, Dmitry A. Kunin A50 The use of LED radiation in prevention of dental diseases Natalia S. Moiseeva, Yury A. Ippolitov, Dmitry A. Kunin, Alexei N. Morozov, Natalia V. Chirkova, Nakhid T. Aliev A51 Status of endothelial progenitor cells in diabetic nephropathy: predictive and preventive potentials Mahmood S. Mozaffari, Jun Yao Liu, Babak Baban A52 The status of glucocorticoid-induced leucine zipper protein in salivary gland in Sjögren’s syndrome: predictive and personalized treatment potentials Mahmood S. Mozaffari, Jun Yao Liu, Rafik Abdelsayed, Xing-Ming Shi, Babak Baban A53 Maximal aerobic capacity - important quality marker of health Jaroslav Novák, Milan Štork, Václav Zeman A54 The EMPOWER project: laboratory medicine and Horizon 2020 Wytze P. Oosterhuis, Elvar Theodorsson A55 Personality profile manifestations in patient’s attitude to oral care and adherence to doctor’s prescriptions Lyudmila Y. Orekhova, Tatyana V. Kudryavtseva, Elena R. Isaeva, Vadim V. Tachalov, Ekaterina S. Loboda A56 Results of an European survey on personalized medicine addressed to directions of laboratory medicine Mario Pazzagli, Francesca Malentacchi, Irene Mancini, Ivan Brandslund, Pieter Vermeersch, Matthias Schwab, Janja Marc, Ron H.N. van Schaik, Gerard Siest, Elvar Theodorsson, Chiara Di Resta A57 MCI or early dementia predictive speech based diagnosis techniques Matus Pleva, Jozef Juhar A58 Personalized speech based mobile application for eHealth Matus Pleva, Jozef Juhar A59 Circulating tumor cell-free DNA as the biomarker in the management of cancer patients Jiří Polívka jr., Filip Janků, Martin Pešta, Jan Doležal, Milena Králíčková, Jiří Polívka A60 Complex stroke care – educational programme in Stroke Centre University Hospital Plzen Jiří Polívka, Alena Lukešová, Nina Müllerová, Petr Ševčík, Vladimír Rohan A61 Sleep apnea and sleep fragmentation contribute to brain aging Kneginja Richter, Lence Miloseva, Günter Niklewski A62 Personalised approach for sleep disturbances in shift workers Kneginja Richter, Jens Acker, Guenter Niklewski A63 Medical travel and innovative PPPM clusters: new concept of integration Olga Safonicheva, Vincenzo Costigliola A64 Medical travel and women health Olga Safonicheva A65 Continuity of generations in the training of specialists in the field of reconstructive microsurgery Maxim Sautin, Janna Sinelnikova, Sergey Suchkov A66 Telemonitoring of stroke patients – empirical evidence of individual risk management results from an observational study in Germany Songül Secer, Stephan von Bandemer A67 Women’s increasing breast cancer risk with n-6 fatty acid intake explained by estrogen-fatty acid interactive effect on DNA damage: implications for gender-specific nutrition within personalized medicine Niva Shapira A68 Cytobacterioscopy of the gingival crevicular fluid as a method for preventive diagnosis of periodontal diseases Aleksandr Shcherbakov, Anatoly A. Kunin, Natalia S. Moiseeva A69 Use of specially treated composites in dentistry to avoid violations of aesthetics Bogdan R. Shumilovich, Zhanna Lipkind, Yulia Vorobieva, Dmitry A. Kunin, Anastasiia V. Sudareva A70 National eHealth system – platform for preventive, predictive and personalized diabetes care Ivica Smokovski, Tatjana Milenkovic A72 The common energy levels of Prof. Szent-Györgyi, the intrinsic chemistry of melanin, and the muscle physiopathology. Implications in the context of Preventive, Predictive, and Personalized Medicine Arturo Solís-Herrera, María del Carmen Arias-Esparza, Sergey Suchkov A73 Plurality and individuality of hepatocellular carcinoma: PPPM perspectives Krishna Chander Sridhar, Olga Golubnitschaja A74 Strategic aspects of higher medical education reforms to secure newer educational platforms for getting biopharma professionals matures Maria Studneva, Sihong Song, James Creeden, Мark Мandrik, Sergey Suchkov A75 Overview of the strategies and activities of the European Federation of Clinical Chemistry and Laboratory Medicine, (EFLM) Elvar Theodorsson, EFLM A76 New spectroscopic techniques for point of care label free diagnostics Syed A. M. Tofail A77 Tumor markers for personalized medicine and oncology - the role of Laboratory Medicine Ondřej Topolčan, Judita Kinkorová, Ondřej Fiala, Marie Karlíková, Šárka Svobodová, Radek Kučera, Radka Fuchsová, Vladislav Třeška, Václav Šimánek, Ladislav Pecen, Jan Šoupal, Štěpán Svačina2 A78 Modern medical terminology (MMT) as a driver of the global educational reforms Evgeniya Tretyak, Maria Studneva, Sergey Suchkov A79 Juvenile hypertension; the relevance of novel predictive, preventive and personalized assessment of its determinants Francesca M. Trovato, G. Fabio Martines, Daniela Brischetto, Daniela Catalano, Giuseppe Musumeci, Guglielmo M. Trovato A80 Proteomarkers Biotech George Th. Tsangaris, Athanasios K. Anagnostopoulos A81 Proteomics and mass spectrometry based non-invasive prenatal testing of fetal health and pregnancy complications George Th. Tsangaris, Athanasios K. Anagnostopoulos A82 Integrated Ecosystem for an Integrated Care model for Heart Failure (HF) patients including related comorbidities (ZENITH) José Verdú, German Gutiérrez, Jordi Rovira, Marta Martinez, Lutz Fleischhacker, Donna Green, Arthur Garson, Elena Tamburini, Stefano Cuomo, Juan Martinez-Leon, Teresa Abrisqueta, Hans-Peter Brunner-La Rocca, Tiny Jaarsma, Teresa Arredondo, Cecilia Vera, Giuseppe Fico, Olga Golubnitschaja, Fernando Arribas, Martina Onderco, Isabel Vara, on behalf of ZENITH consortium A83 Predictive, preventive and personalized medicine in diabetes onset and complication (MOSAIC project) José Verdú, Francesco Sambo, Barbara Di Camillo, Claudio Cobelli, Andrea Facchinetti, Giuseppe Fico, Riccardo Bellazzi, Lucia Sacchi, Arianna Dagliati, Daniele Segnani, Valentina Tibollo, Manuel Ottaviano, Rafael Gabriel, Leif Groop, Jacqueline Postma, Antonio Martinez, Liisa Hakaste, Tiinamaija Tuomi, Konstantia Zarkogianni, on behalf of MOSAIC consortium A84 Possibilities for personalized therapy of diabetes using in vitro screening of insulin and oral hypoglycemic agents Igor Volchek, Nina Pototskaya, Andrey Petrov A85 The innovative technology for personalized therapy of human diseases based on in vitro drug screening Igor Volchek, Nadezhda Pototskaya, Andrey Petrov A86 Bone destruction and temporomandibular joint: predictive markers, pathogenetic aspects and quality of life Ülle Voog-Oras, Oksana Jagur, Edvitar Leibur, Priit Niibo, Triin Jagomägi, Minh Son Nguyen, Chris Pruunsild, Dagmar Piikov, Mare Saag A87 Sub-optimal health management – global vision for concepts in medical travel Wei Wang A88 Sub-optimal health management: synergic PPPM-TCAM approach Wei Wang A89 Innovative technologies for minimal invasive diagnostics Andreas Weinhäusel, Walter Pulverer, Matthias Wielscher, Manuela Hofner, Christa Noehammer, Regina Soldo, Peter Hettegger, Istvan Gyurjan, Ronald Kulovics, Silvia Schönthaler, Gabriel Beikircher, Albert Kriegner, Stephan Pabinger, Klemens Vierlinger A90 Rare disease diobanks for personalized medicine Ayşe Yüzbaşıoğlu, Meral Özgüç, Member of EuroBioBank - European Network of DNA, Cell and Tissue Banks for Rare Diseases
Tumour angiogenesis is an essential process for supplying rapidly growing malignant tissues with essential nutrients and oxygen. An angiogenic switch allows tumour cells to survive and grow, and provides them access to vasculature resulting in metastatic disease. Monocyte-derived macrophages recruited and reprogrammed by tumour cells serve as a major source of angiogenic factors boosting the angiogenic switch. Tumour endothelium releases angiopoietin-2 and further facilitates recruitment of TIE2 receptor expressing monocytes (TEM) into tumor sites. Tumour-associated macrophages (TAM) sense hypoxia in avascular areas of tumours, and react by production of angiogenic factors such as VEGFA. VEGFA stimulates chemotaxis of endothelial cells (EC) and macrophages. In some tumours, TAM appeared to be a major source of MMP9. Elevated expression of MMP9 by TAM mediates extracellular matrix degradation and the release of bioactive VEGFA. Other angiogenic factors released by TAM include bFGF, thymidine phosphorylase (TP), urokinase-type plasminogen activator (uPA), and adrenomedullin. The same factors used by macrophages for the induction of angiogenesis (like VEGF-A and MMP9) support lymphangiogenesis. TAM can express LYVE-1, one of the established markers of lymphatic endothelium. TAM support tumour lymphangiogenesis not only by secretion of pro-lymphangiogenic factors but also by trans-differentiation into lymphatic EC. New pro-angiogenic factor YKL-40 belongs to a family of mammalian chitinase-like proteins (CLP) that act as cytokines or growth factors. Human CLP family comprises YKL-40, YKL-39 and SI-CLP. Production of all three CLP in macrophages is antagonistically regulated by cytokines. It was recently established that YKL-40 induces angiogenesis in vitro and in animal tumour models. YKL-40-neutralizing monoclonal antibody blocks tumour angiogenesis and progression. The role of YKL-39 and SI-CLP in tumour angiogenesis and lymphangiogenesis remains to be investigated.
Major problems with biomedical devices in particular implants located in nonsterile environments concern: (i) excessive immune response to the implant, (ii) development of bacterial biofilms, and (iii) yeast and fungi infections. An original multifunctional coating that addresses all these issues concomitantly is developed. A new exponentially growing polyelectrolyte multilayer film based on polyarginine (PAR) and hyaluronic acid (HA) is designed. The films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophage subpopulations. This could reduce potential chronic inflammatory reaction following implantation. Next, it is shown that PAR, due to its positive charges, has an antimicrobial activity in film format against Staphylococcus aureus for 24 h. In order to have a long‐term antimicrobial activity, a precursor nanoscale silver coating is deposited on the surface before adding the PAR/HA films. Moreover, the PAR/HA films can be easily further functionalized by embedding antimicrobial peptides, like catestatin (CAT), a natural host defense peptide. This PAR/HA+CAT film proves to be effective as an antimicrobial coating against yeast and fungi and its cytocompatibility is also assessed. Finally, this all‐in‐one system constitutes an original strategy to limit inflammation and prevents bacteria, yeast, and fungi infections.
Abstract Implants and medical devices are efficient and practical therapeutic solutions for a multitude of pathologies. Titanium and titanium alloys are used in orthopedics, dentistry, and cardiology. Despite very good mechanical properties and corrosion resistance, titanium implants can fail due to inflammatory or tissue degradation–related complications. Macrophages are major immune cells that control acceptance of failure of the implant. In this study, for the first time, we have performed a systematic analysis of the response of differentially activated human macrophages, M(Control), M(IFNγ), and M(IL-4), to the polished and porous titanium surfaces in order to identify the detrimental effect of titanium leading to the tissue destruction and chronic inflammation. Transcriptome analysis revealed that the highest number of differences between titanium and control settings are found in M(IL-4) that model healing type of macrophages. Real-time quantitative polymerase chain reaction analysis confirmed that both polished and porous titanium affected expression of cytokines, chitinases/chitinase-like proteins, and matrix metalloproteinases (MMPs). Titanium-induced release and activation of MMP7 by macrophages was enhanced by fibroblasts in both juxtacrine and paracrine cell interaction models. Production of titanium-induced MMPs and cytokines associated with chronic inflammation was independent of the presence of Staphylococcus aureus. MMP7, one of the most pronounced tissue-destroying factors, and chitinase-like protein YKL-40 were expressed in CD68+ macrophages in peri-implant tissues of patients with orthopedic implants. In summary, we demonstrated that titanium induces proinflammatory and tissue-destructing responses mainly in healing macrophages, and the detrimental effects of titanium surfaces on implant-adjacent macrophages are independent on the bacterial contamination.
A rare case of benign peritoneal strumosis was screened for driver mutations in genes relevant to currently approved cancer therapies. Therefore, three formalin fixed paraffin embedded issue sections were screened with the GeneReader Actionable Insights NGS panel (Qiagen, Hilden, Germany) for the occurrence of driver mutations. Several mutations were identified in drug-targetable genes, such as ALK, EGFR, and BRAF. The majority of identified mutations were single nucleotide variant, but also a insertion/deletion mutation was identified. The presented dataset is the first NGS dataset available from a patient with benign peritoneal strumosis.
Nowadays implants and medical devices are seen as efficient and practical solutions for a multitude of health associated problems. Titanium and titanium alloys have been successfully used in orthopedics, dentistry, cardiology and otorhinolaryngology. Superior mechanical properties, excellent corrosion resistance, low magnetic susceptibility and high biocompatibility have been the reason for choosing titanium for implantation. Still, up to 9% of implants fail due to the development of various complications. A major cause of implant failure is aseptic loosening, characterized by a progressive destruction of the periprosthetic tissue as a result of foreign body response. Macrophages are essential cells involved in the recognition of the foreign body and in the initiation and coordination of the foreign body response. In order to investigate the extent of macrophage reaction to titanium, human peripheral blood monocyte-derived macrophages were cultured with polished and porous titanium discs. To simulate different macrophage activation states and to discriminate among their reactions to titanium, macrophages were brought to 3 distinct activation states: M(Control), M(IFNγ) and M(IL-4). ELISA analysis revealed that both polished and porous titanium discs induce similar inflammatory cytokine profiles in macrophages. Affymetrix microarray analysis revealed a total of 1690 genes were differentially regulated by polished titanium and 4648 genes were differentially regulated by porous titanium. In both experiments, the highest number of differences between titanium and control settings were found in M(IL-4). Microarray analysis showed that both polished and porous titanium affected several genes involved in inflammation and matrix remodeling. RT-qPCR analysis confirmed that polished titanium up-regulates CSF1, TNFSF14, CHI3L1 and MMP9 and down-regulates CCL8, CCL13, CCL18, CCL23 and IL17RB in M(IL-4) macrophages. Likewise, porous titanium up-regulates the expression of CHIT1, CHI3L1, MMP8 and MMP9 and suppresses CCL8, CCL13, CCL18, CCL23 and IL17RB in M(IL-4) macrophages. Additionally, in order to model wear debris, titanium microbeads and nanoparticles were used. RT-qPCR analysis demonstrated that nanoparticles induce stronger up-regulation of CSF1, CHIT1 and CHI3L1 and stronger down-regulation of CCL8, CCL13, CCL18, and CCL23 when compared to polished titanium discs or to titanium microbeads. In summary, it was demonstrated that titanium induces pro-inflammatory and tissue-remodeling responses first of all in M(IL-4) macrophages, that model healing macrophages. This can explain failure of implants on later stages of implant integration.
In order to simulate a bacterial infection of titanium implants, heat killed Staphylococcus Aureus were added to mature macrophages and naive monocytes cultured with polished titanium discs. Cytokine release analysis revealed that when Staphylococcus Aureus is added to naive monocytes higher levels of TNFα, IL-1β, IL-6, IL-8, CCL18, MMP-7 and MMP-9 are secreted. However, the reaction to Staphylococcus Aureus is not affected by titanium.
In order to examine the effect of peripheral blood mononuclear cells and fibroblasts on the secretion of MMP-7 and MMP-9 by macrophages in response to titanium, co-culture models were established. MMP-7 and MMP-9 secretion levels were increased when the whole fraction of peripheral blood mononuclear cells was exposed to titanium. However, depletion of CD14+ monocytes abrogated this effect. Similarly, fibroblasts stimulated the secretion of MMP-7 in both juxtacrine and paracrine macrophage-fibroblast interaction models. In contrast, MMP-9 secretion was inhibited by fibroblasts in the juxtacrine interaction model. Still, neither peripheral blood mononuclear cells nor fibroblasts were able to substantially increase the concentration of active MMP-7 and MMP-9 in response to titanium.
To increase implant biocompatibility implant coatings can be applied. In this study two types of coatings have been used: polyarginine/hyaluronic acid-based coatings and polylactic acid-based coatings. To test macrophage reaction to these coatings the secretion of TNFα and CCL18 was analyzed. Polyarginine/hyaluronic acid-based coatings inhibited the secretion of TNFα and CCL18 in all donors analyzed. In contrast, the reaction of macrophages to polylactic acid-based coatings was donor-dependent.
Collectively the results of this study indicate that macrophage reaction to titanium implants is determined by several factors: 1) macrophage activation state; 2) titanium surface; 3) titanium size; 4) other cellular components of the periprosthetic tissue; 5) donor-specific factors. However, macrophage reaction to Staphylococcus Aureus is independent of titanium. Furthermore, analysis of macrophage responses to the main implant material as well as to coating materials in a donor-specific way represents a promising approach for the selection of optimal personalized implant materials.
