Controlled release of simvastatin from in situ forming hydrogel triggers bone formation in MC3T3-E1 cells.

Published

Journal Article

Simvastatin (SIM), a drug commonly administered for the treatment of hypercholesterolemia, has been recently reported to induce bone regeneration/formation. In this study, we investigated the properties of hydrogel composed of gelatin-poly(ethylene glycol)-tyramine (GPT) as an efficient SIM delivery vehicle that can trigger osteogenic differentiation. Sustained delivery of SIM was achieved through its encapsulation in an injectable, biodegradable GPT-hydrogel. Cross-linking of the gelatin-based GPT-hydrogel was induced by the reaction of horse radish peroxidase and H(2)O(2). GPT-hydrogels of three different matrix stiffness, 1,800 (GPT-hydrogel1), 5,800 (GPT-hydrogel2), and 8,400 Pa (GPT-hydrogel3) were used. The gelation/degradation time and SIM release profiles of hydrogels loaded with two different concentrations of SIM, 1 and 3 mg/ml, were also evaluated. Maximum swelling times of GPT-hydrogel1, GPT-hydrogel2, and GPT-hydrogel3 were observed to be 6, 12, and 20 days, respectively. All GPT-hydrogels showed complete degradation within 55 days. The in vitro SIM release profiles, investigated in PBS buffer (pH 7.4) at 37°C, exhibited typical biphasic release patterns with the initial burst being more rapid with GPT-hydrogel1 compared with GPT-hydrogel3. Substantial increase in matrix metalloproteinase-13, osteocalcin expression levels, and mineralization were seen in osteogenic differentiation system using MC3T3-E1 cells cultured with GPT-hydrogels loaded with SIM in a dose-dependent manner. This study demonstrated that controlled release of SIM from a biodegradable, injectable GPT-hydrogel had a promising role for long-term treatment of chronic degenerative diseases such as disc degenerative disease.

Full Text

Duke Authors

Cited Authors

  • Park, YS; David, AE; Park, KM; Lin, C-Y; Than, KD; Lee, K; Park, JB; Jo, I; Park, KD; Yang, VC

Published Date

  • April 2013

Published In

Volume / Issue

  • 15 / 2

Start / End Page

  • 367 - 376

PubMed ID

  • 23250670

Pubmed Central ID

  • 23250670

Electronic International Standard Serial Number (EISSN)

  • 1550-7416

Digital Object Identifier (DOI)

  • 10.1208/s12248-012-9442-6

Language

  • eng

Conference Location

  • United States