Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation.

Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation.
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使用带有明胶微球的壳聚糖凝胶顺序递送BMP-2和IGF-1可以增强早期成骨细胞分化。

DOI:
10.1016/j.actbio.2012.01.009
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发表时间:
2012-05
期刊:
影响因子:
9.7
通讯作者:
Yang, Yunzhi
Yang, Yunzhi
中科院分区:
工程技术1区
文献类型:
--
作者:
Kim, Sungwoo;Kang, Yunqing;Krueger, Chad A.;Sen, Milan;Holcomb, John B.;Chen, Di;Wenke, Joseph C.;Yang, Yunzhi

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本研究的目的是开发和表征壳聚糖凝胶/明胶微球(MS)的双重递送系统,用于顺序释放骨形态发生蛋白-2(BMP-2)和胰岛素样生长因子-1(IGF-1),以促进体外成骨细胞分化。我们根据其交联程度、降解和释放动力学制备并表征了递送系统。我们还评估了细胞毒性的交付系统和生长因子对细胞反应的影响,使用前成骨细胞W-20-17小鼠骨髓基质细胞。首先将IGF-1负载到MS中,然后将含有IGF-1的MS包封到含有BMP-2的壳聚糖凝胶中。明胶与乙二醛通过席夫碱交联显着增加了热稳定性,降低了MS的溶解度,导致IGF-1的初始释放显着减少。将MS包封到壳聚糖凝胶中通过分子间相互作用产生了脂质体复合物,这进一步影响了IGF-1的释放动力学。该组合递送系统提供BMP-2的初始释放,随后是IGF-1的缓慢和持续释放。在培养一周后,发现用顺序递送系统处理的W-20-17细胞中的碱性磷酸酶活性显著高于其他处理(p<0.05)。
The purpose of this study was to develop and characterize a chitosan gel/gelatin microspheres (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1 containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system than other treatments (p<0.05) after a week of culture.
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