Multifunctional antimicrobial chlorhexidine polymers by remote plasma assisted vacuum deposition

Abstract

Novel antibacterial materials for implants and medical instruments are essential to develop practical strategies to stop the spread of healthcare associated infections. This study presents the synthesis of multifunctional antibacterial nanocoatings on polydimethylsiloxane (PDMS) by remote plasma assisted deposition of sublimated chlorhexidine powders at low pressure and room temperature. The obtained materials present effective antibacterial activity against Escherichia coli K12, either by contact killing and antibacterial adhesion or by biocide agents release depending on the synthetic parameters. In addition, these multifunctional coatings allow the endure hydrophilization of the hydrophobic PDMS surface, thereby improving their biocompatibility. Importantly, cell-viability tests conducted on these materials also prove their non-cytotoxicity, opening a way for the integration of this type of functional plasma films in biomedical devices.

Graphical abstract

Keywords

plasma polymers / conformal plasma deposition, chlorhexidine, bactericide, PDMS, biocompatibility

References

[1] Cavallaro A A, Macgregor-Ramiasa M N, Vasilev K. Antibiofouling properties of plasma-deposited oxazoline-based thin films. ACS Applied Materials & Interfaces, 2016, 8(10): 6354–6362

[2] Vähä-Nissi M, Pitkänen M, Salo E, Kenttä E, Tanskanen A, Sajavaara T, Putkonen M, Sievänen J, Sneck A, Rättö M, Karppinen M, Harlin A. Antibacterial and barrier properties of oriented polymer films with ZnO thin films applied with atomic layer deposition at low temperatures. Thin Solid Films, 2014, 562: 331–337

[3] Zhang B, Myers D, Wallace G, Brandt M, Choong P. Bioactive coatings for orthopaedic implants—recent trends in development of implant coatings. International Journal of Molecular Sciences, 2014, 15(7): 11878–11921

[4] Banerjee I, Pangule R C, Kane R S. Antifouling coatings: Recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Advanced Materials, 2011, 23(6): 690–718

[5] Gilabert-Porres J, Martí S, Calatayud L, Ramos V, Rosell A, Borrós S. Design of a nanostructured active surface against gram-positive and gram-negative bacteria through plasma activation and in situ silver reduction. ACS Applied Materials & Interfaces, 2016, 8(1): 64–73

[6] Jiang F, Yeh C K, Wen J, Sun Y. N-Trimethylchitosan/alginate layer-by-layer self assembly coatings act as ‘fungal repellents’ to prevent biofilm formation on healthcare materials. Advanced Healthcare Materials, 2015, 4(3): 469–475

[7] Li L, Pu T, Zhanel G, Zhao N, Ens W, Liu S. New biocide with both n-chloramine and quaternary ammonium moieties exerts enhanced bactericidal activity. Advanced Healthcare Materials, 2012, 1(5): 609–620

[8] Wu M, He J, Ren X, Cai W S, Fang Y C, Feng X Z. Development of functional biointerfaces by surface modification of polydimethylsiloxane with bioactive chlorogenic acid. Colloids and Surfaces. B, Biointerfaces, 2014, 116: 700–706

[9] Yu Q, Wu Z, Chen H. Dual-function antibacterial surfaces for biomedical applications. Acta Biomaterialia, 2015, 16: 1–13

[10] Agarwal A, Nelson T B, Kierski P R, Schurr M J, Murphy C J, Czuprynski C J, McAnulty J F, Abbott N L. Polymeric multilayers that localize the release of chlorhexidine from biologic wound dressings. Biomaterials, 2012, 33(28): 6783–6792

[11] He T, Zhang Y, Lai A C K, Chan V. Engineering bio-adhesive functions in an antimicrobial polymer multilayer. Biomedical Materials (Bristol, England), 2015, 10(1): 15015

[12] Verraedt E, Braem A, Chaudhari A, Thevissen K, Adams E, Van Mellaert L, Cammue B P A, Duyck J, Anné J, Vleugels J, Martens J A. Controlled release of chlorhexidine antiseptic from microporous amorphous silica applied in open porosity of an implant surface. International Journal of Pharmaceutics, 2011, 419(1-2): 28–32

[13] Yu Q, Ge W, Atewologun A, Stiff-Roberts A D, López G P. Antimicrobial and bacteria-releasing multifunctional surfaces: Oligo (p-phenylene-ethynylene)/poly (N-isopropylacrylamide) films deposited by RIR-MAPLE. Colloids and Surfaces. B, Biointerfaces, 2015, 126: 328–334

[14] Chang C H, Yeh S Y, Lee B H, Hsu C W, Chen Y C, Chen C J, Lin T J, Chen M H C, Huang C T, Chen H Y. Compatibility balanced antibacterial modification based on vapor-deposited parylene coatings for biomaterials. Journal of Materials Chemistry. B, Materials for Biology and Medicine, 2014, 2(48): 8496–8503

[15] Nikiforov A Y, Deng X, Onyshchenko I, Vujosevic D, Vuksanovic V, Cvelbar U, De Geyter N, Morent R, Leys C. Atmospheric pressure plasma deposition of antimicrobial coatings on non-woven textiles. European Physical Journal Applied Physics, 2016, 75(2): 24710

[16] Ostrikov K, Levchenko I, Keidar M, Cvelbar U, Mariotti D, Mai-Prochnow A, Fang J. Novel biomaterials: Plasma-enabled nanostructures and functions. Journal of Physics. D, Applied Physics, 2016, 49(27): 273001

[17] Barranco A, Groening P. Fluorescent plasma nanocomposite thin films containing nonaggregated rhodamine 6G laser dye molecules. Langmuir, 2006, 22(16): 6719–6722

[18] Barranco A, Aparicio F, Yanguas-Gil A, Groening P, Cotrino J, González-Elipe A R. Optically active thin films deposited by plasma polymerization of dye molecules. Chemical Vapor Deposition, 2007, 13(6-7): 319–325

[19] Aparicio F J, Holgado M, Borras A, Blaszczyk-Lezak I, Griol A, Barrios C A, Casquel R, Sanza F J, Sohlstrom H, Antelius M, González-Elipe A R, Barranco A. Transparent nanometric organic luminescent films as UV-active components in photonic structures. Advanced Materials, 2011, 23(6): 761–765

[20] Aparicio F J, Alcaire M, González-Elipe A R, Barranco A, Holgado M, Casquel R, Sanza F J, Griol A, Bernier D, Dortu F, Cáceres S, Antelius M, Lapisa M, Sohlström H, Niklaus F. Dye-based photonic sensing systems. Sensors and Actuators. B, Chemical, 2016, 228: 649–657

[21] Blaszczyk-Lezak I, Aparicio F J, Borrás A, Barranco A, Álvarez-Herrero A, Fernández-Rodríguez M, González-Elipe A R. Optically active luminescent perylene thin films deposited by plasma polymerization. Journal of Physical Chemistry C, 2009, 113(1): 431–438

[22] Aparicio F J, Alcaire M, Borras A, Gonzalez J C, López-Arbeloa F, Blaszczyk-Lezak I, González-Elipe A R, Barranco A. Luminescent 3-hydroxyflavone nanocomposites with a tuneable refractive index for photonics and UV detection by plasma assisted vacuum deposition. Journal of Materials Chemistry. C, Materials for Optical and Electronic Devices, 2014, 2(32): 6561–6573

[23] Sangamesh K, Laurencin C, Deng M, eds. Natural and Synthetic Biomedical Polymers. San Diego: Elsevier, 2014, 301–308

[24] Chen H, Brook M A, Sheardown H. Silicone elastomers for reduced protein adsorption. Biomaterials, 2004, 25(12): 2273–2282

[25] Thevenot P, Hu W, Tang L. Surface chemistry influences implant biocompatibility. Current Topics in Medicinal Chemistry, 2008, 8(4): 270–280

[26] Gilbert P, Allison D G, Brading M, Verran J, Walker J. Biofilm community interactions: Chance or necessity? Cardiff: Bioline, 2001, 11–22

[27] Wilson C J, Clegg R E, Leavesley D I, Pearcy M J. Mediation of biomaterial-cell interactions by adsorbed proteins: A review. Tissue Engineering, 2005, 11(1-2): 1–18

[28] Zhang H, Chiao M. Anti-fouling Coatings of poly(dimethylsiloxane) devices for biological and biomedical applications. Journal of Medical and Biological Engineering, 2014, 35(2): 143–155

[29] Larson B J, Gillmor S D, Braun J M, Cruz-Barba L E, Savage D E, Denes F S, Lagally M G. Long-term reduction in poly(dimethylsiloxane) surface hydrophobicity via cold-plasma treatments. Langmuir, 2013, 29(42): 12990–12996

[30] Forster S, McArthur S L. Stable low-fouling plasma polymer coatings on polydimethylsiloxane. Biomicrofluidics, 2012, 6(3): 036504

[31] Lee D, Yang S. Surface modification of PDMS by atmospheric-pressure plasma-enhanced chemical vapor deposition and analysis of long-lasting surface hydrophilicity. Sensors and Actuators. B, Chemical, 2012, 162(1): 425–434

[32] Kaelble D H. Dispersion-polar surface tension properties of organic solids. Journal of Adhesion, 1970, 2(2): 66–81

[33] Owens D K, Wendt R C. Estimation of the surface free energy or polymers. Journal of Applied Polymer Science, 1969, 13(8): 1741–1747

[34] Balouiri M, Sadiki M, Ibnsouda S K. Methods for in vitro evaluating antimicrobial activity: A review. Journal of Pharmaceutical Analysis, 2016, 6(2): 71–79

[35] Mestieri L B, Gomes-Cornélio A L, Rodrigues E M, Faria G, Guerreiro-Tanomaru J M, Tanomaru-Filho M. Cytotoxicity and bioactivity of calcium silicate cements combined with niobium oxide in different cell lines. Brazilian Dental Journal, 2017, 28(1): 65–71

[36] Aparicio F J, Borras A, Blaszczyk-Lezak I, Gröning P, Álvarez-Herrero A, Fernández-Rodríguez M, González-Elipe A R, Barranco A. Luminescent and optical properties of nanocomposite thin films deposited by remote plasma polymerization of Rhodamine 6G. Plasma Processes and Polymers, 2009, 6(1): 17–26

[37] Aparicio F J, Blaszczyk-Lezak I, Sánchez-Valencia J R, Alcaire M, González J C, Serra C, González-Elipe A R, Barranco A. Plasma deposition of perylene-adamantane nanocomposite thin films for NO₂ room-temperature optical sensing. Journal of Physical Chemistry C, 2012, 116(15): 8731–8740

[38] Beamson G, Briggs D. High Resolution XPS of Organic Polymers. New York: John Wiley & Sons Ltd., 1990, 277–287

[39] Yim J H, Fleischman M S, Rodriguez-Santiago V, Piehler L T, Williams A A, Leadore J L, Pappas D D. Development of antimicrobial coatings by atmospheric pressure plasma using a guanidine-based precursor. ACS Applied Materials & Interfaces, 2013, 5(22): 11836–11843

[40] Yook J Y, Lee M, Song K H, Jun J, Kwak S. Surface modification of poly(ethylene-2,6-naphthalate) using NH₃ plasma. Macromolecular Research, 2014, 22(5): 534–540

[41] Aparicio F J, Thiry D, Laha P, Snyders R. Wide range control of the chemical composition and optical properties of propanethiol plasma polymer films by regulating the deposition temperature. Plasma Processes and Polymers, 2016, 13(8): 814–822

[42] Jiang H, Grant J T, Enlow J, Su W, Bunning T J. Surface oxygen in plasma polymerized films. Journal of Materials Chemistry, 2009, 19(15): 2234–2239

[43] Sokrates G. Infrared and Raman Characteristic Group Frequencies: Tables and Charts. New York: Wiley-Interscience, 2001, 191–198

[44] Kovtun A, Kozlova D, Ganesan K, Biewald C, Seipold N, Gaengler P, Arnold W H, Epple M. Chlorhexidine-loaded calcium phosphatenanoparticles for dental maintenance treatment: Combination of mineralising and antibacterial effects. RSC Advances, 2012, 2(3): 870–875

[45] Badea M, Olar R, Iliş M, Georgescu R, Călinescu M. Synthesis, characterization, and thermal decomposition of new copper (II) complex compounds with chlorhexidine. Journal of Thermal Analysis and Calorimetry, 2012, 111(3): 1763–1770

[46] Pal S, Tak Y K, Han E, Rangasamy S, Song J M. A multifunctional composite of an antibacterial higher-valent silver metallopharmaceutical and a potent wound healing polypeptide: A combined killing and healing approach to wound care. New Journal of Chemistry, 2014, 38(8): 3889–3898

[47] Holešová S, Valášková M, Hlaváč D, Madejová J, Samlíková M, Tokarský J, Pazdziora E. Antibacterial kaolinite/urea/chlorhexidine nanocomposites: Experiment and molecular modelling. Applied Surface Science, 2014, 305: 783–791

[48] Biederman H, ed. Plasma Polymer Films. London: Imperial College Press, 2004, 227–231

[49] Labay C, Canal J M, Modic M, Cvelbar U, Quiles M, Armengol M, Arbos M A, Gil F J, Canal C. Antibiotic-loaded polypropylene surgical meshes with suitable biological behaviour by plasma functionalization and polymerization. Biomaterials, 2015, 71: 132–144

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