title: Poloxamine-cyclodextrin-simvastatin supramolecular systems promote osteoblast differentiation of mesenchymal stem cells.
abstract: Osteogenic/osteoinductive systems combine simvastatin, poloxamine Tetronic 908 (T908) and α-cyclodextrins (αCDs) in a supramolecular network that enhances the solubility/stability of the simvastatin hydroxy acid form and synergistically promotes osteoblast differentiation. Incorporation of 5% αCD transforms dilute T908 solutions (as low as 2% copolymer) into gels, enhances the osteoinductive activity of T908, and provides simvastatin sustained release for more than one week, which results in higher and more prolonged alkaline phosphatase (ALP) activity. The performance of the intrinsically osteoinductive polypseudorotaxane scaffold can be easily tuned by modifying the concentrations of T908, αCD, and simvastatin in a certain range of values. Moreover, the use of affordable, stable materials that can be sterilized applying a conventional method make the supramolecular gels advantageous candidates as scaffolds to be applied in the critical defect using minimally invasive techniques.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548-Coimbra, Portugal.
authors.forename: Susana M N
authors.initials: SM
authors.lastname: Simões
authors.forename: Francisco
authors.initials: F
authors.lastname: Veiga
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Torres-Labandeira
authors.forename: Ana Cristina F
authors.initials: AC
authors.lastname: Ribeiro
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects; D004355:Drug Stability; D055119:Elastic Modulus / Q000187:drug effects; D005029:Ethylenediamines / Q000494:pharmacology*; D005782:Gels; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D044367:Phase Transition / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology*; D019821:Simvastatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013997:Time Factors; D047391:alpha-Cyclodextrins / Q000494:pharmacology*
chemical_list: D005029:Ethylenediamines; D005782:Gels; D047391:alpha-Cyclodextrins; C532833:simvastatin hydroxyacid; C012571:tetronic 701; D011092:Polyethylene Glycols; D019821:Simvastatin; D000469:Alkaline Phosphatase