Minimizing the passive release of heparin-binding growth factors from an affinity-based delivery system.
Minimizing the passive release of heparin-binding growth factors from an affinity-based delivery system.
复制标题
最大限度地减少基于亲和力的递送系统中肝素结合生长因子的被动释放。
DOI：
10.1093/imammb/dqs027
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
M. Meere
中科院分区：
文献类型：
--
作者：
Tuoi T. Vo;M. Meere
我们考虑一个数学模型，该模型描述了肝素结合生长因子从基于亲和力的递送系统中的泄漏。在递送系统中，肝素与已与纤维蛋白基质共价交联的肽结合。生长因子又与肝素结合，生长因子的释放受到结合和扩散机制的控制，结合的目的是减缓生长因子的释放。控制数学模型的原始公式由六个偏微分方程组成，现在被简化为仅包含两个方程的系统。通常希望生长因子不会从装置中被动释放，所有生长因子都通过结合保持在适当的位置，直到它被入侵细胞主动释放为止。然而，不可避免地会出现一些被动释放，因此有必要确定使该释放尽可能缓慢的条件。在本文中，我们确定了一个参数机制，确保至少一部分生长因子会缓慢释放。发现如果制备基质时交联肽的浓度大大超过肝素与肽的解离常数，并且肝素的浓度大大超过生长因子与肝素的解离常数，则可以保证缓慢释放。此外，首次将体外实验释放数据与模型生成的理论释放曲线进行直接比较。我们认为，实验中常见的两阶段释放行为是由于游离生长因子在扩散时间尺度（通常为数天）内最初快速向外扩散，随后结合部分在时间尺度上缓慢释放，具体取决于扩散和结合参数（通常为数月）。
We consider a mathematical model that describes the leakage of heparin-binding growth factors from an affinity-based delivery system. In the delivery system, heparin binds to a peptide which has been covalently cross-linked to a fibrin matrix. Growth factor in turn binds to the heparin, and growth factor release is governed by both binding and diffusion mechanisms, the purpose of the binding being to slow growth factor release. The governing mathematical model, which in its original formulation consists of six partial differential equations, is reduced to a system of just two equations. It is usually desirable that there be no passive release of growth factor from a device, with all of the growth factor being held in place via binding until such time as it is actively released by invading cells. However, there will inevitably be some passive release, and so it is of interest to identify conditions that will make this release as slow as possible. In this paper, we identify a parameter regime that ensures that at least a fraction of the growth factor will release slowly. It is found that slow release is assured if the matrix is prepared with the concentration of cross-linked peptide greatly exceeding the dissociation constant of heparin from the peptide, and with the concentration of heparin greatly exceeding the dissociation constant of the growth factor from heparin. Also, for the first time, in vitro experimental release data are directly compared with the theoretical release profiles generated by the model. We propose that the two stage release behaviour frequently seen in experiments is due to an initial rapid out-diffusion of free growth factor over a diffusion time scale (typically days), followed by a much slower release of the bound fraction over a time scale depending on both diffusion and binding parameters (frequently months).
通过生物物理和生物测定以及肽-五糖对接复合物的分子模型评估抗凝血酶 III-肝素相互作用的结构-功能关系。
DOI：
10.1006/abbi.1996.0448
发表时间：
1996
期刊：
Archives of biochemistry and biophysics.
影响因子：
--
作者：
Tyler-Cross,R;Sobel,M;McAdory,LE;Harris,RB
通讯作者：
Harris,RB