Controlled Release of Simvastatin from In situ Forming Hydrogel Triggers Bone Formation in MC3T3-E1 Cells

摘要: 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 properties hydrogel composed gelatin–poly(ethylene glycol)–tyramine (GPT) as an efficient SIM delivery vehicle that can trigger osteogenic differentiation. Sustained was achieved through its encapsulation in injectable, biodegradable GPT-hydrogel. Cross-linking gelatin-based GPT-hydrogel induced by reaction horse radish peroxidase and H2O2. GPT-hydrogels three different matrix stiffness, 1,800 (GPT-hydrogel1), 5,800 (GPT-hydrogel2), 8,400 Pa (GPT-hydrogel3) were used. The gelation/degradation time release profiles hydrogels loaded with two concentrations SIM, 1 3 mg/ml, also evaluated. Maximum swelling times GPT-hydrogel1, GPT-hydrogel2, GPT-hydrogel3 observed be 6, 12, 20 days, respectively. All showed complete degradation within 55 days. vitro profiles, PBS buffer (pH 7.4) at 37°C, exhibited typical biphasic patterns initial burst being more rapid GPT-hydrogel1 compared GPT-hydrogel3. Substantial increase metalloproteinase-13, osteocalcin expression levels, mineralization seen differentiation system using MC3T3-E1 cells cultured dose-dependent manner. This study demonstrated controlled from biodegradable, injectable had promising role long-term chronic degenerative diseases such disc disease.