title: Novel anti-infective implant substrates: controlled release of antibiofilm compounds from mesoporous silica-containing macroporous titanium.
abstract: Bone implants with open porosity enable fast osseointegration, but also present an increased risk of biofilm-associated infections. We design a novel implant material consisting of a mesoporous SiO2 diffusion barrier (pore diameter: 6.4 nm) with controlled drug release functionality integrated in a macroporous Ti load-bearing structure (fully interconnected open porosity: 30%; pore window size: 0.5-2.0 μm). Using an in vitro tool consisting of Ti/SiO2 disks in an insert set-up, through which molecules can diffuse from feed side to release side, a continuous release without initial burst effect of the antibiofilm compound toremifene is sustained for at least 9 days, while release concentrations (up to 17 μM daily) increase with feed concentrations (up to 4mM). Toremifene diffusivity through the SiO2 phase into H2O is estimated around 10(-13)m(2)/s, suggesting configurational diffusion through mesopores. Candida albicans biofilm growth on the toremifene-release side is significantly inhibited, establishing a proof-of-concept for the drug delivery functionality of mesoporous SiO2 incorporated into a high-strength macroporous Ti carrier. Next-generation implants made of this composite material and equipped with an internal reservoir (feed side) can yield long-term controlled release of antibiofilm compounds, effectively treating infections on the implant surface (release side) over a prolonged time.
authors.affiliation: Department of Materials Engineering (MTM), KU Leuven, Kasteelpark Arenberg 44 Box 2450, 3001 Leuven, Belgium. Electronic address: Annabel.Braem@mtm.kuleuven.be.
authors.forename: Annabel
authors.initials: A
authors.lastname: Braem
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20 Box 2460, 3001 Leuven, Belgium; Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent, Belgium. Electronic address: Kaat.Decremer@biw.kuleuven.be.
authors.forename: Kaat
authors.initials: K
authors.lastname: De Cremer
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20 Box 2460, 3001 Leuven, Belgium. Electronic address: Nicolas.Delattin@biw.kuleuven.be.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delattin
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20 Box 2460, 3001 Leuven, Belgium. Electronic address: Katrijn.Debrucker@biw.kuleuven.be.
authors.forename: Katrijn
authors.initials: K
authors.lastname: De Brucker
authors.affiliation: Department of Materials Engineering (MTM), KU Leuven, Kasteelpark Arenberg 44 Box 2450, 3001 Leuven, Belgium. Electronic address: Bram.Neirinck@mtm.kuleuven.be.
authors.forename: Bram
authors.initials: B
authors.lastname: Neirinck
authors.affiliation: BIOMAT Research Cluster, Department of Oral Health Sciences and Prosthetic Dentistry, KU Leuven and University Hospitals Leuven, Kapucijnenvoer 7 Box 7001, 3000 Leuven, Belgium. Electronic address: Katleen.Vandamme@med.kuleuven.be.
authors.forename: Katleen
authors.initials: K
authors.lastname: Vandamme
authors.affiliation: Centre of Surface Chemistry and Catalysis (COK), KU Leuven, Kasteelpark Arenberg 23 Box 2461, 3001 Leuven, Belgium. Electronic address: Johan.Martens@biw.kuleuven.be.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20 Box 2460, 3001 Leuven, Belgium. Electronic address: Jan.Michiels@biw.kuleuven.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Michiels
authors.affiliation: Department of Materials Engineering (MTM), KU Leuven, Kasteelpark Arenberg 44 Box 2450, 3001 Leuven, Belgium. Electronic address: Jozef.Vleugels@mtm.kuleuven.be.
authors.forename: Jef
authors.initials: J
authors.lastname: Vleugels
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20 Box 2460, 3001 Leuven, Belgium; Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent, Belgium. Electronic address: Bruno.Cammue@biw.kuleuven.be.
authors.forename: Bruno P A
authors.initials: BP
authors.lastname: Cammue
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20 Box 2460, 3001 Leuven, Belgium. Electronic address: Karin.Thevissen@biw.kuleuven.be.
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D065546:Drug Liberation; D008826:Microbial Sensitivity Tests; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry*; D017312:Toremifene / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D012822:Silicon Dioxide; D017312:Toremifene; D014025:Titanium
keywords: Biofilm prevention; Candida albicans; Controlled release; Mesoporous silica; Porous titanium; Toremifene