title: Controlled release of chlorhexidine from a mesoporous silica-containing macroporous titanium dental implant prevents microbial biofilm formation.
abstract: Roughened surfaces are increasingly being used for dental implant applications as the enlarged contact area improves bone cell anchorage, thereby facilitating osseointegration. However, the additional surface area also entails a higher risk for the development of biofilm associated infections, an etiologic factor for many dental ailments, including peri-implantitis. To overcome this problem, we designed a dental implant composed of a porous titanium-silica (Ti/SiO2) composite material and containing an internal reservoir that can be loaded with antimicrobial compounds. The composite material consists of a sol-gel derived mesoporous SiO2 diffusion barrier integrated in a macroporous Ti load-bearing structure obtained by powder metallurgical processing. The antimicrobial compounds can diffuse through the porous implant walls, thereby reducing microbial biofilm formation on the implant surface. A continuous release of µM concentrations of chlorhexidine through the Ti/SiO2 composite material was measured, without initial burst effect, over at least 10 days and using a 5 mM chlorhexidine solution in the implant reservoir. Metabolic staining, CFU counting and visualisation by scanning electron microscopy confirmed that Streptococcus mutans biofilm formation on the implant surface was almost completely prevented due to chlorhexidine release (preventive setup). Moreover, we demonstrated efficacy of released chlorhexidine against mature Streptococcus mutans biofilms (curative setup). In conclusion, we provide a proof of concept of the sustained release of chlorhexidine, one of the most widely used oral antiseptics, through the Ti/SiO2 material thereby preventing and eradicating biofilm formation on the surface of the dental implant. In principle, our flexible design allows for the use of any bioactive compound, as discussed.
authors.forename: K
authors.initials: K
authors.lastname: De Cremer
authors.forename: A
authors.initials: A
authors.lastname: Braem
authors.forename: E
authors.initials: E
authors.lastname: Gerits
authors.forename: K
authors.initials: K
authors.lastname: De Brucker
authors.forename: K
authors.initials: K
authors.lastname: Vandamme
authors.forename: J A
authors.initials: JA
authors.lastname: Martens
authors.forename: J
authors.initials: J
authors.lastname: Michiels
authors.forename: J
authors.initials: J
authors.lastname: Vleugels
authors.forename: B P
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.karin.thevissen@kuleuven.be.
authors.forename: K
authors.initials: K
authors.lastname: Thevissen
mesh_terms: D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D045744:Cell Line, Tumor; D002710:Chlorhexidine / Q000008:administration & dosage* / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D015921:Dental Implants; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D016062:Porosity; D011474:Prosthesis Design; D012822:Silicon Dioxide / Q000737:chemistry*; D013295:Streptococcus mutans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D014025:Titanium / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; D015921:Dental Implants; D012822:Silicon Dioxide; D014025:Titanium; D002710:Chlorhexidine