In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering.
In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering.
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DOI：
10.1155/2017/6434169
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发表时间：
2017
影响因子：
--
通讯作者：
Lee J
中科院分区：
文献类型：
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作者：
Kim BS;Shkembi F;Lee J
阿仑膦酸钠（ALN）是一种双膦酸盐药物，广泛用于治疗骨质疏松症。此外，ALN的局部递送具有改善骨再生的潜力。本研究旨在研究含ALN的纤维蛋白（纤维蛋白/ALN）凝胶，并评估该凝胶对使用人间充质干细胞（hMSCs）的体外细胞行为和体内骨再生能力的影响。使用各种ALN浓度（10 - 7-10 - 4 M）与纤维蛋白胶制备纤维蛋白水凝胶，并表征形态、机械性能和ALN释放动力学。检测纤维蛋白/ALN凝胶包埋的hMSCs的增殖、成骨分化及细胞毒性。使用兔颅骨缺损模型评价体内骨形成。所制备的纤维蛋白/ALN凝胶是透明的，杨氏模量为~13 kPa，并且这些性质不受ALN浓度的影响。体外研究显示ALN从纤维蛋白凝胶中持续释放，并显示在纤维蛋白/ALN凝胶中培养的hMSCs显示出显著增加的增殖和成骨分化。此外，显微计算机断层扫描和组织学分析显示，在颅骨缺损模型中植入纤维蛋白/ALN凝胶后，新形成的骨显著增强。这些结果表明，纤维蛋白/ALN具有改善骨再生的潜力。
Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10−7–10−4 M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.