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Synthesis and characterization of a fluvastatin-releasing hydrogel delivery system to modulate hMSC differentiation and function for bone regeneration

Paper ID Volume ID Publish Year Pages File Format Full-Text
11278 729 2006 9 PDF Available
Title
Synthesis and characterization of a fluvastatin-releasing hydrogel delivery system to modulate hMSC differentiation and function for bone regeneration
Abstract

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 μg 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 μM 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.

Keywords
Controlled drug release; Statin; Mesenchymal stem cells; Bone tissue engineering
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Synthesis and characterization of a fluvastatin-releasing hydrogel delivery system to modulate hMSC differentiation and function for bone regeneration
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 27, Issue 36, December 2006, Pages 6102–6110
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us