Multi-loaded ceramic beads/matrix scaffolds obtained by combining ionotropic and freeze gelation for sustained and tuneable vancomycin release.
For a targeted release against bacteria-associated bone diseases (osteomyelitis) ceramic beads with a high drug loading capacity, loaded with vancomycin as model antibiotic, are synthesized as drug carrier and successfully incorporated in an open porous hydroxyapatite matrix scaffold via freeze gelation to prevent bead migration at the implantation site and to extend drug release. We demonstrate that the quantity of loaded drug by the hydroxyapatite and β-tricalcium phosphate beads, produced by ionotropic gelation, as well as drug release can be tuned and controlled by the selected calcium phosphate powder, sintering temperature, and high initial vancomycin concentrations (100mg/ml) used for loading. Bead pore volume up to 68mm(3)/g, with sufficiently large open pores (pore size of up to 650nm with open porosity of 72%) and high surface area (91m(2)/g) account likewise for a maximum drug loading of 236mg/g beads or 26mg/sample. Multi-drug loading of the beads/matrix composite can further increase the maximum loadable amount of vancomycin to 37mg/sample and prolong release and antibacterial activity on Bacillus subtilis up to 5days. The results confirmed that our approach to incorporate ceramic beads as drug carrier for highly increased drug load in freeze-gelated matrix scaffolds is feasible and may lead to a sustained drug release and antibacterial activity.
Advanced Ceramics, University of Bremen, Am Biologischen Garten 2, 28359 Bremen, Germany. Electronic address: uhess@uni-bremen.de.
Ulrike
U
Hess
Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Measuring and Automation Technology, TU Dresden, George-Baehr-Strasse 3, 01069 Dresden, Germany. Electronic address: gerd.mikolajczyk1@tu-dresden.de.
Gerd
G
Mikolajczyk
Advanced Ceramics, University of Bremen, Am Biologischen Garten 2, 28359 Bremen, Germany. Electronic address: treccanilaura@gmail.com.
Laura
L
Treccani
Department for Cranio-Maxillofacial and Plastic Surgery, University Hospital of Giessen-Marburg GmbH, Campus Giessen, Klinikstrasse 33, 35392 Giessen, Germany; Laboratory of Experimental Surgery, Justus-Liebig-University of Giessen, Kerkrader Strasse 9, 35394 Giessen, Germany. Electronic address: philipp.streckbein@uniklinikum-giessen.de.
Philipp
P
Streckbein
Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg GmbH, Campus Giessen, Rudolf-Buchheim-Strasse 7, 35392 Giessen, Germany; Laboratory of Experimental Surgery, Justus-Liebig-University of Giessen, Kerkrader Strasse 9, 35394 Giessen, Germany. Electronic address: christian.heiss@chiru.med.uni-giessen.de.
Christian
C
Heiss
Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Measuring and Automation Technology, TU Dresden, George-Baehr-Strasse 3, 01069 Dresden, Germany. Electronic address: stefan.odenbach@tu-dresden.de.
Stefan
S
Odenbach
Advanced Ceramics, University of Bremen, Am Biologischen Garten 2, 28359 Bremen, Germany; MAPEX Center for Materials and Processes, University of Bremen, Am Fallturm 1, 28359 Bremen, Germany. Electronic address: krezwan@uni-bremen.de.
Kurosch
K
Rezwan
D001412:Bacillus subtilis / Q000254:growth & development*; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology; D002516:Ceramics / Q000737:chemistry / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D016062:Porosity; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology
D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; C485817:beta-tricalcium phosphate; D014640:Vancomycin
Beads; Drug carrier; Drug release; Hydroxyapatite; Scaffold; Vancomycin