title: Bioinspired Titanium Drug Eluting Platforms Based on a Poly-β-cyclodextrin-Chitosan Layer-by-Layer Self-Assembly Targeting Infections.
abstract: In the field of implantable titanium-based biomaterials, infections and inflammations are the most common forms of postoperative complications. The controlled local delivery of therapeutics from implants through polyelectrolyte multilayers (PEMs) has recently emerged as a versatile technique that has shown great promise in the transformation of a classical medical implant into a drug delivery system. Herein, we report the design and the elaboration of new biodegradable multidrug-eluting titanium platforms based on a polyelectrolyte multilayer bioactive coating that target infections. These systems were built up in mild conditions according to the layer-by-layer (L-b-L) assembly and incorporate two biocompatible polysaccharides held together through electrostatic interactions. A synthetic, negatively charged β-cyclodextrin-based polymer (PCD), well-known for forming stable and reversible complexes with hydrophobic therapeutic agents, was exploited as a multidrug reservoir, and chitosan (CHT), a naturally occurring, positively charged polyelectrolyte, was used as a barrier for controlling the drug delivery rate. These polyelectrolyte multilayer films were strongly attached to the titanium surface through a bioinspired polydopamine (PDA) film acting as an adhesive first layer and promoting the robust anchorage of PEMs onto the biomaterials. Prior to the multilayer film deposition, the interactions between both oppositely charged polyelectrolytes, as well the multilayer growth, were monitored by employing surface plasmon resonance (SPR). Several PEMs integrating 5, 10, and 15 bilayers were engineered using the dip coating strategy, and the polyelectrolyte surface densities were estimated by colorimetric titrations and gravimetric analyses. The morphologies of these multilayer systems, as well as their naturally occurring degradation in a physiological medium, were investigated by scanning electron microscopy (SEM), and their thicknesses were measured by means of profilometry and ellipsometry studies. Finally, the ability of the coated titanium multilayer devices to act as a drug-eluting system and to treat infections was validated with gentamicin, a relevant water-soluble antibiotic commonly used in medicine due to its broad bactericidal spectrum.
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pérez-Anes
authors.affiliation: ‡U 1008 INSERM Médicaments et Biomatériaux à Libération Contrôlée, Faculté de Médecine, Université Lille 2, 59045 Lille, France.
authors.forename: Myriem
authors.initials: M
authors.lastname: Gargouri
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: William
authors.initials: W
authors.lastname: Laure
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Van Den Berghe
authors.affiliation: ‡U 1008 INSERM Médicaments et Biomatériaux à Libération Contrôlée, Faculté de Médecine, Université Lille 2, 59045 Lille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Courcot
authors.affiliation: ‡U 1008 INSERM Médicaments et Biomatériaux à Libération Contrôlée, Faculté de Médecine, Université Lille 2, 59045 Lille, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sobocinski
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tabary
authors.affiliation: ‡U 1008 INSERM Médicaments et Biomatériaux à Libération Contrôlée, Faculté de Médecine, Université Lille 2, 59045 Lille, France.
authors.forename: Feng
authors.initials: F
authors.lastname: Chai
authors.affiliation: §Unité de Catalyse et de Chimie du Solide (UCCS, UMR CNRS 8181), Faculté des Sciences Jean Perrin, Université d'Artois, rue Jean Souvraz, SP18, 62307 Lens Cedex, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Blach
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Addad
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Woisel
authors.affiliation: ∥Medway School of Science at Medway, University of Greenwich, Chatham Maritime, ME4 4TB Kent, U.K.
authors.forename: Dennis
authors.initials: D
authors.lastname: Douroumis
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Martel
authors.affiliation: ‡U 1008 INSERM Médicaments et Biomatériaux à Libération Contrôlée, Faculté de Médecine, Université Lille 2, 59045 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchemain
authors.affiliation: †Unité des Matériaux Et Transformations (UMET, UMR 8207), Equipe Ingénierie des Systèmes Polymères (ISP), Université Lille 1, 59655 Villeneuve d'Ascq, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Lyskawa
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005839:Gentamicins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles; D050296:Microbial Viability / Q000187:drug effects; D011108:Polymers; D013211:Staphylococcus aureus / Q000187:drug effects; D020349:Surface Plasmon Resonance; D014025:Titanium / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D005839:Gentamicins; D007211:Indoles; D011108:Polymers; D047392:beta-Cyclodextrins; C571277:chitosan-beta-cyclodextrin; C568283:polydopamine; D048271:Chitosan; D014025:Titanium
keywords: antibacterial coating; chitosan; cyclodextrin-based polymer; drug delivery system; polydopamine; polyelectrolyte multilayer; titanium