Harnessing the multifunctionality in nature: a bioactive agent release system with self-antimicrobial and immunomodulatory properties
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1
INSERM, Unit 1121 Biomaterials and Bioengineering, France
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2
Protip Medical, France
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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: 602694
References:
[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
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.