Microparticle-embedded fibroin/alginate beads for prolonged local release of simvastatin hydroxyacid to mesenchymal stem cells. (1st November 2017) - Ungaro, F.
Graphical abstract: Highlights: Simvastatin was efficiently encapsulated in PLGA-based microparticles by spray-drying. PLGA microparticles released osteogenic simvastatin hydroxyacid (SVA). SVA concentration and microparticle formulation affected MSC proliferation and differentiation. PLGA microparticles were embedded in fibroin/alginate beads alleviating SVA burst. Microparticle-embedded fibroin/alginate beads promoted MSC differentiation into osteoblasts. Abstract: In the present work, we propose silk fibroin/alginate (SF/Alg) beads embedding simvastatin-loaded biodegradable microparticles as a versatile platform capable of tuning SVA release and in so doing osteogenic effects. In a first part of the study, microparticles of poly(lactic-co-glycolic) acid incorporating simvastatin either as lactone (SVL) or as hydroxyacid form (SVA) were prepared by spray-drying. While SVA-loaded microparticles released the drug in three days, long-term release of SVA could be obtained from SVL-loaded microparticles. In this latter case, SVL was promptly transformed to the osteogenic active SVA during release. When tested on mesenchymal stem cells, a time- and dose-dependent effect of SVL-loaded microparticles on cell proliferation and alkaline phosphatase (ALP) activity was found. Thereafter, SVL-loaded microparticles were embedded in SF/Alg beads to limit the initial simvastatin burst and to achieve easier implantation as well. Microparticle-embedded beads showed no cytotoxicity while ALP activity increased. If correctly exploited, the developed system may be suitable as osteogenic polymer scaffolds releasing correct amount of the drug locally for long time-frames.