Antibiotic-loaded Sr-doped porous calcium phosphate granules as multifunctional bone grafts

abstract

Multifunctional porous calcium phosphate granules intended as osseous fillers and drug carriers were designed. Strontium- and magnesium-co-substituted biphasic hydroxyapatite (HA)/beta-tricalcium phosphate powders (TCP) with compositions close to the mineral part of human bone [(Ca+Sr+Mg)/P=1.62] were prepared by precipitation, heat treated and deagglomerated, and characterized by XRD and SEM. Highly concentrated aqueous suspensions (up to 60 vol%) were prepared from the powders heat treated at 1000 degrees C. Starch was added as pore forming agent and the suspensions were dripped into a setting sodium alginate solution to obtain spherical granules. Drying and sintering enabled obtaining porous granules that were impregnated with an antibiotic solution (levofloxacin), frozen and then lyophilized. The drug release profile was then assessed in vitro by UV spectrophotometry, with the best release profile being obtained for the Sr-doped granules. The granules' osteocompatibility was evaluated using a pre-osteoblastic cell line. The Sr-doped granules exhibited the highest proliferation yields and efficiency in osteoblastic maturation, including acquisition of a differentiated morphology and high levels of secreted alkaline phosphatase. The microstructural features and the in vitro performance of the granules make them promising multifunctional materials for applications in tissue engineering as antibiotic-loaded bone grafts. (C) 2015 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

keywords

BETA-TRICALCIUM PHOSPHATE; IN-VIVO; DRUG-DELIVERY; PORE-SIZE; STARCH CONSOLIDATION; GENTAMICIN-RELEASE; CRYSTAL-STRUCTURE; ARTIFICIAL BONE; HYDROXYAPATITE; OSTEOMYELITIS

subject category

Materials Science

authors

Marques, CF; Lemos, A; Vieira, SI; Silva, OABDE; Bettencourt, A; Ferreira, JMF

our authors

acknowledgements

This work was supported by the European Regional Development Fund (FEDER) under the PT2020 Partnership Agreement through the COMPETE, by the Portuguese Government through the Portuguese Foundation for Science and Technology (FCT), in the scope of the projects UID/CTM/50011/2013 (Aveiro Institute of Materials, CICECO, www.ciceco.ua.pt), the Institute for Biomedicine iBiMED UID/BIM/04501/2013, and CBC PEst-OE/SAU/UI0482/2014, Research Units of the University of Aveiro. The first author is also thankful to FCT for the fellowship Grant reference SFRH/BD/78355/2011.

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