title: Composite material consisting of microporous β-TCP ceramic and alginate for delayed release of antibiotics.
abstract: The aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28days.
  
  
  
  Using the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10mL double-distilled water for 4weeks at 37°C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA.
  
  
  
  The release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2±1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14days. The burst release here was 61.9±4.3%. The native alginate's burst release was 54.1±7.8%; that of the sterile alginate 40.5±6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5-2.0μg/mL against Staphylococcus aureus.
  
  
  
  Drug release systems based on β-TCP and hydrogels are well documented in literature. However, in all described systems the ceramic, as granule or powder, is inserted into a hydrogel. In our work, we do the opposite, a hydrogel which acts as reservoir for antibiotics is placed into a porous biodegradable ceramic. Eventually, this system should be applied as treatment of bone infections. Contrary to the "granule in hydrogel" composites it has the advantage of mechanical stability. Thus, it can take over functions of the bone during the healing process. For a quicker translation from our scientific research into clinical use, only FDA approved materials were used in this work.
authors.affiliation: Center of Surgery, Department of Orthopedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany. Electronic address: michael.seidenstuecker@uniklinik-freiburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Seidenstuecker
authors.affiliation: University of Freiburg, IMTEK, Department of Microsystems Engineering, Chemistry and Physics of Interfaces, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Ruehe
authors.affiliation: Center of Surgery, Department of Orthopedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Norbert P
authors.initials: NP
authors.lastname: Suedkamp
authors.affiliation: Medical Center University of Freiburg, Institute for Microbiology and Hygiene, Germany.
authors.forename: Annerose
authors.initials: A
authors.lastname: Serr
authors.affiliation: Medical Center University of Freiburg, Institute for Microbiology and Hygiene, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Wittmer
authors.affiliation: RMS Foundation, Bettlach, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Bohner
authors.affiliation: Center of Surgery, Department of Orthopedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Bernstein
authors.affiliation: Center of Surgery, Department of Orthopedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Hermann O
authors.initials: HO
authors.lastname: Mayr
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002516:Ceramics / Q000737:chemistry*; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations / Q000494:pharmacology; D065546:Drug Liberation; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D012212:Rheology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D000464:Alginates; D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; C485817:beta-tricalcium phosphate; D014640:Vancomycin; D020723:Glucuronic Acid
keywords: Alginate; Beta tricalcium phosphate; Composite; Delayed release; Drug delivery system; Drug release; Flow chamber; Vancomycin