Gelatin microspheres crosslinked with genipin for local delivery of growth factors.
Gelatin microspheres crosslinked with genipin for local delivery of growth factors.
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DOI：
10.1002/term.267
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发表时间：
2010-10
影响因子：
3.3
通讯作者：
Stegemann, Jan P.
中科院分区：
文献类型：
--
作者：
Solorio, Luis;Zwolinski, Christopher;Lund, Amanda W.;Farrell, Megan J.;Stegemann, Jan P.
组织工程和再生医学的主要挑战是实现局部和有效的生长因子释放以引导细胞功能。明胶是一种变性形式的胶原蛋白，细胞可以结合并通过酶促作用降解。本研究采用明胶微球释放骨形态发生蛋白2（BMP 2）。通过乳化过程产生直径在2-6 μm范围内的球形微粒，并通过与小分子京尼平交联来稳定。通过控制京尼平溶液中的孵育时间来改变交联程度。加载速率研究，使用大豆胰蛋白酶抑制剂作为模型蛋白质，显示在第一个24小时内快速的蛋白质摄取，然后平稳，然后在大约3天后进一步增加，因为微球膨胀。使用交联至20%、50%和80%饱和度然后装载BMP 2的微球的生长因子释放研究表明，较高的交联度导致较高的装载效率和较慢的蛋白质释放。24小时后，所有微球制剂产生的浓度曲线稳定且大致相等。与成人间充质干细胞孵育的微球优先在细胞表面积累，并在培养中随时间降解。在培养14天后，BMP-2微球引起骨唾液酸蛋白基因表达增加3 - 8倍，交联珠越多，效果越好。这些结果表明京尼平交联明胶微球可用于将生长因子局部递送至细胞以指导其功能。
A main challenge in tissue engineering and regenerative medicine is achieving local and efficient growth factor release to guide cell function. Gelatin is a denatured form of collagen that cells can bind to and degrade through enzymatic action. In this study, gelatin microspheres were used to release bone morphogenetic protein 2 (BMP2). Spherical microparticles with diameters in the range of 2–6 µm were created by an emulsification process and were stabilized by crosslinking with the small molecule genipin. The degree of crosslinking was varied by controlling the incubation time in genipin solution. Loading rate studies, using soy bean trypsin inhibitor as a model protein, showed rapid protein uptake over the first 24 h, followed by a levelling off and then a further increase after approximately 3 days, as the microspheres swelled. Growth factor release studies using microspheres crosslinked to 20%, 50% and 80% of saturation and then loaded with BMP2 showed that higher degrees of crosslinking resulted in higher loading efficiency and slower protein release. After 24 h, the concentration profiles produced by all microsphere formulations were steady and approximately equal. Microspheres incubated with adult human mesenchymal stem cells accumulated preferentially on the cell surface, and degraded over time in culture. BMP2-loaded microspheres caused a three- to eight-fold increase in expression of the bone sialoprotein gene after 14 days in culture, with more crosslinked beads producing a greater effect. These results demonstrate that genipin-crosslinked gelatin microspheres can be used to deliver growth factors locally to cells in order to direct their function.
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DOI：
10.1016/j.ijbiomac.2006.04.010
发表时间：
2006-11-15
影响因子：
8.2
作者：
Nickerson, M. T.;Patel, J.;Paulson, A. T.
通讯作者：
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影响因子：
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影响因子：
2.8
作者：
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影响因子：
14
作者：
Hong, Helen;McCullough, Caltlyn M.;Stegemann, Jan P.
通讯作者：
Stegemann, Jan P.
影响因子：
9.7
作者：
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