Document Detail

Synthesis and characterization of a fluvastatin-releasing hydrogel delivery system to modulate hMSC differentiation and function for bone regeneration.
MedLine Citation:
PMID:  16860387     Owner:  NLM     Status:  MEDLINE    
Increases in bone formation have been demonstrated in mice and rats treated with statins, a group of molecules that increase the production of bone morphogenetic proteins-2 (BMP2) by stimulating its promoter. However, clinical use of statins (e.g., fluvastatin) is limited by the lack of a suitable delivery system to localize and sustain release. To harness the therapeutic effect of statins in orthopedic applications, a fluvastatin-releasing macromer was synthesized. When copolymerized with a dimethacrylated poly(ethylene glycol) solution, this fluvastatin-containing molecule was covalently incorporated into hydrogel networks, and hydrolysis of lactic acid ester bonds resulted in the release of the pendantly tethered fluvastatin from the hydrogel into the surrounding solution. The rate of fluvastatin release was controlled by the length of lactic acid spacer (2-6 repeats), and the dose was controlled by the initial comonomer composition (5-500 microg fluvastatin/gel). Released fluvastatin increased human mesenchymal stem cell (hMSC) gene expression of CBFA1, ALP, and COL I by 34-fold, 2.6-fold, and 1.8-fold, respectively, after 14 days of in vitro culture. In addition, treating hMSCs with the released fluvastatin resulted in an average of 2.0- and 1.5-fold greater BMP2 production whereas mineralization increased an average of 3.0-fold and 2.5-fold for 0.01 and 0.1 microM fluvastatin, respectively, over the 2 week culture period. Therefore, fluvastatin-releasing hydrogels may be useful in bone tissue engineering applications, not only for triggering osteogenic differentiation of hMSCs, but also by modulating their function.
Danielle S W Benoit; Charles R Nuttelman; Stuart D Collins; Kristi S Anseth
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-07-24
Journal Detail:
Title:  Biomaterials     Volume:  27     ISSN:  0142-9612     ISO Abbreviation:  Biomaterials     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-09-25     Completed Date:  2006-12-13     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  6102-10     Citation Subset:  IM    
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MeSH Terms
Biocompatible Materials / chemistry
Bone Regeneration / drug effects,  physiology*
Cell Culture Techniques / methods
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Delayed-Action Preparations / administration & dosage,  chemistry
Fatty Acids, Monounsaturated / administration & dosage*,  chemistry
Hydrogels / chemistry
Indoles / administration & dosage*,  chemistry
Materials Testing
Mesenchymal Stromal Cells / cytology*,  drug effects,  physiology*
Osteoblasts / cytology*,  drug effects,  physiology
Osteogenesis / drug effects,  physiology*
Tissue Engineering / methods*
Grant Support
Reg. No./Substance:
0/Biocompatible Materials; 0/Delayed-Action Preparations; 0/Fatty Acids, Monounsaturated; 0/Hydrogels; 0/Indoles; 4L066368AS/fluvastatin

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