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Self-defending polymer surfaces: A new strategy to protect medical devices against infection

English title Self-defending polymer surfaces: A new strategy to protect medical devices against infection
Applicant Palivan Cornelia
Number 156367
Funding scheme China
Research institution Physikalische Chemie Departement Chemie Universität Basel
Institution of higher education University of Basel - BS
Main discipline Physical Chemistry
Start/End 01.08.2015 - 31.07.2019
Approved amount 250'000.00
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Keywords (6)

microstructured surfaces; device associated infections; antibiotics release; antibacterial activity; polymer compartments; amphiphilic copolymers

Lay Summary (French)

Lead
Les infections associées aux implants (IAI), ainsi que les réactions d’incompatibilité et les problèmes liés aux interventions chirurgicales sont les principales causes d’échec des implants modernes, avec des conséquences graves pour la santé des patients et l’augmentation des couts de la santé. Nous avons identifié des applications des implants dans un grand nombre de domaines médicaux (cardiovasculaire, orthopédie, incontinence urinaire, dentaire et ophtalmologie) avec une contribution IAI entre 2 et 40%. Les couts pour la révision des implants infectés entrainent une augmentation significative des couts primaires de l’implantation. Malgré une augmentation des efforts scientifiques pour proposer des stratégies antibactériennes, il n’y pas encore de solution clinique : les quelques exemples d’implants qui contient des composés antibactériens se basent sur une libération de quantités massives d’antibiotiques, ou d’argent en cas d’applications topiques.
Lay summary

Contenu et objectives du travail de recherche

L’objectif principal de ce projet est de produire des surfaces polymères capables d’« auto-défense », basées sur des membranes polymères avec une texture spécifique (stratégie passive), ainsi que l’immobilisation sur ceux-ci de compartiments polymères nanométriques qui vont produire, sur demande, des antibiotiques (stratégie active). Les surfaces dotées d’une texture vont empêcher la localisation des bactéries et les nano-compartiments vont produire des antibiotiques pour détruire localement les bactéries. L’étude systématique de l’impact de la morphologie de la surface, de son architecture, du fonctionnement des nano-réacteurs aux antibiotiques sur les propriétés de ces surfaces avec  « auto-défense », est essentielle pour obtenir ces nouvelles surfaces antibactériennes. 

La complexité du projet de recherche demande des équipes avec des expertises complémentaires dans les domaines suivants : chimie, physique, nanoscience et biologie. Pour résoudre les différentes tâches de recherche du projet, nous allons combiner l’expertise des équipes de l’Université de Bale (Prof. C. Palivan and Prof. W. Meier)  dans la synthèse des polymères et le développement de systèmes hybrides de dimensions nanométriques, avec celle de l’équipe du partenaire chinois de l’Institute de Chimie de l’Académie Chinoise des Sciences (Prof. J. Xu) pour le domaine des surfaces à textures contrôlées.

Contexte scientifique et social du project de recherche

L’objectif de ces recherches conjointes sera d’améliorer la protection contre les IAI en utilisant des biomatériaux à double fonctionnalité avec une stabilité à long terme améliorée. Nos équipes suisse-chinoise vont unir leurs efforts de recherche pour une avancée dans le domaine de surfaces multifonctionnelles aves des propriétés bio-sensibles pour les applications médicales.

Direct link to Lay Summary Last update: 29.05.2018

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Enzymatic reactions in polymeric compartments: nanotechnology meets nature
Belluati Andrea, Craciun Ioana, Meyer Claire E, Rigo Serena, Palivan Cornelia G (2019), Enzymatic reactions in polymeric compartments: nanotechnology meets nature, in Current Opinion in Biotechnology, 60, 53-62.
Surfaces with Dual Functionality through Specific Coimmobilization of Self-Assembled Polymeric Nanostructures
Rigo Serena, Gunkel-Grabole Gesine, Meier Wolfgang, Palivan Cornelia G. (2019), Surfaces with Dual Functionality through Specific Coimmobilization of Self-Assembled Polymeric Nanostructures, in Langmuir, 35(13), 4557-4565.
Biomimetic Planar Polymer Membranes Decorated with Enzymes as Functional Surfaces
Draghici Camelia, Mikhalevich Viktoria, Gunkel-Grabole Gesine, Kowal Justyna, Meier Wolfgang, Palivan Cornelia G. (2018), Biomimetic Planar Polymer Membranes Decorated with Enzymes as Functional Surfaces, in Langmuir, 34(30), 9015-9024.
Nanoscience-Based Strategies to Engineer Antimicrobial Surfaces
Rigo Serena, Cai Chao, Gunkel-Grabole Gesine, Maurizi Lionel, Zhang Xiaoyan, Xu Jian, Palivan Cornelia G. (2018), Nanoscience-Based Strategies to Engineer Antimicrobial Surfaces, in Advanced Science, 5(5), 1700892-1700892.
Porphyrin-polymer nanocompartments: singlet oxygen generation and antimicrobial activity
Lanzilotto Angelo, Kyropoulou Myrto, Constable Edwin C., Housecroft Catherine E., Meier Wolfgang P., Palivan Cornelia G. (2018), Porphyrin-polymer nanocompartments: singlet oxygen generation and antimicrobial activity, in JBIC Journal of Biological Inorganic Chemistry, 23(1), 109-122.
Nanostructured surfaces through immobilization of self-assembled polymer architectures using thiol-ene chemistry
Gunkel-GraboleGesine (2017), Nanostructured surfaces through immobilization of self-assembled polymer architectures using thiol-ene chemistry, in Macromol. Mater. Eng., 302(4), 1600363.
"Active surfaces" as Possible Functional Systems in Detection and Chemical (Bio) Reactivity
Housecroft Ca., Palivan C., Gademann K., Meier W., Calame M., Zhang X., Mikhalevich V., Piel E., Szponarski M., Wiesler A., Lanzilotto A., Constable E.C., Fanget A., Stoop R.L. (2016), "Active surfaces" as Possible Functional Systems in Detection and Chemical (Bio) Reactivity, in Chimia, 6, 402-413.
Bioinspired polymer vesicles and membranes for biological and medical applications
Palivan C., Goers R., Najer A., Zhang X., Meier W. (2016), Bioinspired polymer vesicles and membranes for biological and medical applications, in Chem. Soc. Rev, 45, 377-411.

Collaboration

Group / person Country
Types of collaboration
Prof. J. Xu, Institute of Chemistry, Chinese Academy of Sciences China (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
eCM Conference 2019 Talk given at a conference Functional surfaces based on immobilized polymeric nanostructures 28.06.2019 Davos, Switzerland Palivan Cornelia;
eCM Conference 2109 Poster Nanostructured surfaces based on co-immobilization of polymersomes and micelles on solid support 26.06.2019 Davos, Switzerland Rigo Serena; Palivan Cornelia;
Christmas Symposium 2018 Poster Immobilizing nanostructures through the strain promoted Azide-Alkyne click (SPAAC) reaction 07.12.2018 Basel, Switzerland Palivan Cornelia; Rigo Serena;
Chinese-Swiss Biliteral Workshop Talk given at a conference Creating new types of biointerfaces by combining polymer-based membranes and biomolecules 09.11.2018 Nankai, China Palivan Cornelia;
Antimicrobial Biomaterials and Biofilm Infection: a stepping stone symposium Talk given at a conference Strategies to create smart surfaces by immobilization of nanostructures 19.09.2018 Tianjin, China Rigo Serena;
A stepping stone symposium Talk given at a conference Strategies to create smart surfaces by immobilization of nanostructures 19.09.2018 Tianjin, China Rigo Serena; Palivan Cornelia;
Biointerfaces International Conference Poster Immobilizing nanostructures through the strain promoted Azide-Alkyne click (SPAAC) reaction 14.08.2018 Zurich, Switzerland Rigo Serena; Palivan Cornelia;
Swiss Soft Days 24 Talk given at a conference Immobilizing vesicles through catalyst free click reaction 02.03.2018 PSI, Switzerland Rigo Serena; Palivan Cornelia;
Swiss soft days 22 Poster Immobilization vesicles through catalyst free click reaction 02.03.2018 PSI, Villingen, Switzerland Rigo Serena; Palivan Cornelia;
Invited talk, ICCAS Individual talk “Smart” functional systems for medical applications: polymer nano-assemblies combined with biomolecules 26.10.2017 Beijing, China Xu Jian; Palivan Cornelia;
TechMem International Conference Talk given at a conference Functional membranes based on protein-polymer membranes 07.08.2017 Wien, Austria Palivan Cornelia;
15th BIT Annual Congress, International Drugs Discovery: Science and Technology Talk given at a conference Catalytic nanocompartments as novel solution for protein therapy 25.07.2017 Osaka, Japan Palivan Cornelia;
9th International Conference on Advanced Materials - ROCAM2017 Talk given at a conference "Smart" functional nanosytems: polymer membranes decorated with proteins 10.07.2017 Bucharest, Romania Palivan Cornelia;
COST IPROMEDIA Workshop Talk given at a conference Nanoscience-based active surfaces with antibacterial ativity 20.04.2017 Valletta, Malta Palivan Cornelia;
6th MC meeting and combined Focus Group Meeting COST Action IproMedai Talk given at a conference Nanoscience-based active surfaces with antibacterial activity 18.04.2017 Valetta, Malta Palivan Cornelia; Rigo Serena;
invited lecture Individual talk Protein-polymer supramolecular assemblies: Bio-nano funcional systems 23.01.2017 Tübingen, Germany Palivan Cornelia;
Christmas Symposium 2016 Poster Self-Defending Polymer Surfaces to Prevent Device Associated Infection 30.11.2016 University of Basel, Switzerland Rigo Serena; Zhang Xiaoyan; Palivan Cornelia; Xu Jian;
29th Inernational Microprocesses and Nanotechnology Conference Talk given at a conference Nanodevices based on combining biomolecules with synthetic membranes 08.11.2016 Kyoto, Japan Palivan Cornelia;
3rd iPROMEDAI S&T meeting – Antimicriobal Material & Surfaces Talk given at a conference Antimicrobial Peptide-polymer nanoparticles 08.10.2016 Kusadasi (Turkey) and Samos (Greece), Turkey Rigo Serena; Palivan Cornelia;
ipromedai Summer School – antimicrobial medical devices Poster Active surfaces with anitibacterial effect 09.09.2016 Amsterdam and Groningen, Netherlands Rigo Serena;
International Conference in Physics of Advanced Materials Talk given at a conference “Smart” self-assembled functional nanosystems based on polymer membranes decorated with proteins 08.09.2016 Cluj, Romania Palivan Cornelia;
Swiss Soft Day 19 Talk given at a conference Active Surfaces Engineered by Immobilizing Protein-polymer Nanoreactors for Selectively Detecting Sugar Alcohols 02.09.2016 Basel, Switzerland Zhang Xiaoyan; Palivan Cornelia;
Swiss Soft Days 19 Poster Combining micro-structured Surfaces with antibiotic encapsulated Vesicles to prevent Device Associated Infection 02.09.2016 Basel, Switzerland Zhang Xiaoyan; Xu Jian; Palivan Cornelia; Rigo Serena;
Biointerfaces International 2016 Poster Active Surfaces Engineered by Immobilizing Protein-polymer Nanoreactors for Selectively Detecting Sugar Alcohols 25.08.2016 Zurich, Switzerland Zhang Xiaoyan; Palivan Cornelia;
Biointerfaces International 2016 Poster Self-Defending Polymer Surfaces to Prevent Device Associated Infection 25.08.2016 Zurich, Switzerland Rigo Serena; Palivan Cornelia; Zhang Xiaoyan; Xu Jian;
Biointerfaces International 2016 Talk given at a conference Polymer membranes decorated with biomolecules: Novel systems with medical potential 25.08.2016 zurich, Switzerland Palivan Cornelia;
International Nanoscience Student Conference Talk given at a conference Sugar Alcohol Biosensors based on Polymer-Protein Self-assembled Nanoreactors 02.08.2016 Baarlo, Netherlands Zhang Xiaoyan; Palivan Cornelia;
80th Prague Meeting of macromolecules Talk given at a conference Polymer membranes decorated with proteins: Smart self-assembled functional nanosystems 10.07.2016 Prague, Czech Republic Palivan Cornelia;
Basel Postdoc Network Retreat Talk given at a conference Active Surfaces Engineered by Immobilizing Protein-polymer Nanoreactors for Selectively Detecting Sugar Alcohols 22.06.2016 Saas Fee, Switzerland Palivan Cornelia; Zhang Xiaoyan;
MEET THE EXPERT Implants Poster Nanoscience-based active surfaces with antibacterial activity 25.04.2016 Interlaken, Switzerland Palivan Cornelia; Rigo Serena; Zhang Xiaoyan;


Awards

Title Year
Poster-prize on the Christmas symposium 2016 2016

Associated projects

Number Title Start Funding scheme
140302 PROTEIN-POLYMER SUPRAMOLECULAR ASSEMBLIES IN THE DESIGN OF ANTIOXIDANT NANOREACTORS AND PROCESSORS 01.06.2012 Project funding

Abstract

Device associated infections (DAI), together with incompatibility reactions and surgical deficiencies are the main reasons for failure of modern medical devices in practice, often with severe consequences including high distress for the patients and huge socio-economical costs. We identified device applications in a variety of medical domains, such as cardiovascular, orthopedics, trauma, urinary incontinence, and ophthalmology in which DAI rates range from 2 to 40%. The costs for revision of infected devices are dramatically increasing the original implantation costs. Despite a substantial increase in recent research efforts on antibacterial strategies, there is currently no effective clinical solution. The few antimicrobial active compound containing devices rely on delivery of massive amounts of antibiotics, or on the release of silver which is limited to topical applications. The primary goal our joint collaboration intends to overcome is the complexity of research projects in this field requires a highly complementary team containing expertise across chemistry, physics, nanoscience, and biology. Combining expertise across chemistry, physics, nanoscience, and biology will allow our joint collaboration to overcome the complexity of research projects required in this field.The main objective of this project is to engineer “self-defending” polymer surfaces with a dual functionality based on: 1.) stealth polymer membranes with appropriate topology (passive strategy) and 2) association with immobilized nanoreactors releasing antibiotics “on demand” (active strategy). In such a diverse field, success largely depends on an interdisciplinary approach combining different expertise and knowledge. Therefore, we propose combining the highly complementary research field and infrastructure of the two proposing parties: the Swiss research unit at the University of Basel (Wolfgang Meier and Cornelia G. Palivan groups), in the field of polymer synthesis and development of nanoscale hybrid systems, together with the surface architecture control expertise of our Chinese partner at the Institute of Chemistry, Chinese Academy of Sciences (Jian Xu group).We plan a bottom-up approach to support the synthesis and investigation of various amphiphilic copolymers for the development of controlled bio-responsive surfaces serving to efficiently fight against DAI. First, we will synthesize a library of novel amphiphilic triblock copolymers with stimuli-responsive properties by varying the length of each block, the hydrophilic to hydrophobic ratio, and by modification of the hydrophilic domain with functional groups to support immobilization of their supramolecular assemblies on polymer surfaces with a specific morphology. Copolymers and their superstructures, both in solution and at interfaces, will be characterized by a variety of bulk and surface state of the art techniques. The focus will be on aqueous self-assembly, “grafting-to” approaches, as cost-effective ways to exploit biomimetic and strong multivalent adhesion. First, surface properties after coating with polymer membrane will be controlled by the surface chemical composition, and by an artificially generated biomimetic microstructure inducing a modification of interface interactions. Second, polymer compartments containing antibiotics will be immobilized on polymer coated surfaces by strong covalent interactions of molecular recognition interactions. Finally, antibacterial assays will distinguish the simultaneous impact of surface morphology, architecture, and release of antibiotics on the bio-responsive properties. An expected benefit of the joint research project will be improving protection against DAI by biomaterials/surfaces with dual functionality and improved long-term stability. In addition, the establishment of comprehensive sets of standard test methods with appropriate reference materials will allow for comparison of outcomes and optimization of the antibacterial activity of our “self-defending” surfaces. The proposed research project constitutes a partnership between the Department of Chemistry, University of Basel, and the Institute of Chemistry, Chinese Academy of Sciences that is expected to generate a long term collaboration based on the combination of our complementary expertise with the joint aim to engineer improved materials to fight against DAI. Our project applicants will unify their efforts for an important experimental contribution to the field of multifunctional bio-responsive surfaces with applications in medical technology.
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