Permanent sterile Oberflächen durch Kombination von antimikrobiellen und Biobelag verhindernden Oberflächenstrukturen

• Antragstellerin: Professorin Dr. Karen Lienkamp
• Fachliche Zuordnung: Präparative und Physikalische Chemie von Polymeren
• Förderung: Förderung von 2011 bis 2017
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 189968166

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

Summary of Achievements: We developed two synthetic platforms to make surface-attached polymer networks with precisely tunable properties. By systematically varying charge density and hydrophobicity, we obtained highly active antimicrobial coatings that were compatible with human cells. We systematically characterized the biological and physical properties of these coatings and showed that the antimicrobial activity increases with decreasing acid constant; that cell compatibility increases with increasing swellability. These results led to an important modification in the currently accepted mechanism for antimicrobial activity on surfaces. We developed bifunctional surfaces coating made from protein-repellent poly(zwitterions) that were grafted onto our antimicrobial polymer networks. We could show that these dual-functional coatings were protein resistant and simultaneously active against E. coli bacteria. They are thus promising candidates to make antimicrobial materials that can also prevent biofilm formation. We found the first simultaneously antimicrobial, protein-repellent and cell-compatible poly(zwitterion). Due to the excellent performance of our materials, we started translational research projects. We filed four patents, developed a model for a coated urinary catheter, and coated “real life“ wound dressings with our polymers. We just started to validate the PZI technology for medical applications in a BMBF-funded validation project. We obtained proof-of-concept for self-regenerating antimicrobial surfaces. These consist of a multi-stack of alternating degradable and antimicrobial layers. Like a reptile shedding its skin, the top antimicrobial layer is shed when the degradable layer underneath decomposes. The thus emerging antimicrobial layer from underneath was fully antimicrobially active. This idea and proof-of-concept won us an ERC starting grant. We started to explore new chemistries to make new bioactive monomers and polymers, including poly(norbornene)-based antimicrobial polymers with intended break points in the main chain; antimicrobial polymers based on itaconic acid, a monomer from natural resources; and new biodegradable polymers. „Antimikrobielle Schicht soll Krankenhausinfektionen eindämmen": BioPro, 27.11.2017 „Nicht nur Schlangen häuten sich“. Badische Zeitung, 26.02.2016 „Inspiriert von der Natur - Am Freiburger Institut FIT geht es um smarte Materialien“, Badische Zeitung, 26.02.2016 „Rühren, warten, hoffen“: Südwestpresse, 18. September 2015 „Sich häutende Oberflächen“: chemie.de, 2.12.2014 „Immune Oberfläche“: ChemiePlus, Ausgabe 03/2013, S. 50 „Bakterienkiller mit zwei Gesichtem - Freiburger Forscher entwickeln Alternativen zu Antibiotika“, Deutschlandradio 21.06.2011

Projektbezogene Publikationen (Auswahl)

• "It Takes Walls and Knights to Defend a Castle - How the Combination of Antimicrobial and Antibiofouling Polymers Might Yield Biofilm-resistant Surface Coatings", J. Mat. Chem. 2012, 22, 19579
  P. Zou, W. Hartleb, K. Lienkamp
  
• “Covalently Attached Antimicrobial Polymers”, WO2012089617
  T. Steinberg, P. Tomakidi, K. Lienkamp, A. Al-Ahmad
  
• "Nature-inspired Antimicrobial Polymers - Assessment of Their Potential for Biomedical Applications", PLoS ONE, 2013, 8, e73812
  A. Al-Ahmad, D. Laird, P. Zou, P. Tomakidi, T. Steinberg, K. Lienkamp
  
• “Experimental Setup to Determine the Antibacterial Activity of Surfaces”, WO2013127536
  A. Al-Ahmad, J. Nanko, K. Lienkamp
  
• “Synthesis and Micro- /Nanostructuring of Surface-attached Crosslinked Antimicrobial and/or Antibiofouling polymer Networks”, WO 2013132066
  K. Lienkamp, P. Zou, A. Al-Ahmad, T. Steinberg, P. Tomakidi
  
• "Synthetic Mimics of Antimicrobial Peptides (SMAMPs) - A New Class of Nature-Inspired Antimicrobial Agents with Low Bacterial Resistance", in: A. Munoz-Bonilla, M. Cerrada, M. Femández-Garcia (Eds.) "Polymeric Materials with Antimicrobial Activity: From Synthesis to Applications", RSC Polymer Series No. 10, Royal Society of Chemistry, Cambridge/UK, 2014, 97
  F. Dorner, K. Lienkamp
  
• ‘Towards Self-regenerating Antimicrobial Polymer Surfaces”, ACS Macro Letters 2015, 4, 1337
  F. Dorner, W. Hartleb, A. Al-Ahmad, K. Lienkamp
  
• “Antimicrobial and Cell-Compatible Surface-attached Polymer Networks - How the Correlation of Chemical Stmcture to Physical And Biological Data Leads to a Modified Mechanism of Action”, J. Mat. Chem. B, 2015,3, 6224
  P. Zou, D. Laird, E. K. Riga, Z. Deng, F. Dorner, H.-R. Perez-Hemandez, D. L. Guevara-Solarte, T. Steinberg, A. Al-Ahmad, K. Lienkamp
  
• “Just Antimicrobial Is Not Enough - Towards Bifunctional Polymer Surfaces With Dual Antimicrobial and Protein-repellent Functionality”, Macromol. Chem. Phys. 2016, 277, 225
  W. Hartleb, J. S. Saar, P. Zou, K. Lienkamp
  
• “Synthetic Mimics of Antimicrobial Peptides (SMAMPs) in Layer-by-Layer Architectures: Possibilities and Limitations”, Macromol. Chem. Phys. 2016, 277, 2154
  F. Dorner, A. Malek-Luz, J. S. Saar, S. Bonaus, A. AI-Ahmad, K. Lienkamp
  
• “A Simultaneously Antimicrobial, Protein-repellent and Cell-compatible Polyzwitterion Network”, 2017, 75, 1373
  M. Kurowska, A. Eickenscheidt, D. L. Guevara-Solarte, V. T. Widyaya, F. Marx, A. AI-Ahmad, K. Lienkamp
  
• “Fluorescent ROMP Monomers and Copolymers for Biomedical Applications’’, Macromol. Chem. Phys. 2017, 218, 1700273
  E. K. Riga, D. Boschert, M. Vöhringer, V. T. Widyaya, M. Kurowska, W. Haitleb, K. Lienkamp
  
• “Polymer Having Antimicrobial and/or Antifouling Properties”, WO 2017085069
  K. Lienkamp, D. Boschert, A. Schneider, A. Al-Ahmad
  
• “Polymer-based Surfaces Designed To Reduce Biofilm Formation - From Antimicrobial Polymers to Strategies for Long-Term Applications”, Macromol. Rapid. Commun. 2017, 38, 1700216
  E. K. Riga, M. Vöhringer, V. T. Widyaya, K. Lienkamp