Diffusion-reaction models of genipin incorporation into fibrin networks
Diffusion-reaction models of genipin incorporation into fibrin networks
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DOI：
10.1039/c4tb02025a
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发表时间：
2015-01-01
影响因子：
7
通讯作者：
Bettinger, Christopher J.
中科院分区：
文献类型：
--
作者：
Chi Ninh;Iftikhar, Aimon;Bettinger, Christopher J.
京尼平是一种天然衍生的小分子，其交联含有伯胺的化合物，包括许多天然生物聚合物。提出了一种预测京尼平进入纤维蛋白网络的递送和掺入速率的扩散反应模型。纤维蛋白水凝胶内京尼平交联的形成是一个多步骤的过程，需要京尼平扩散并与水合网络中的伯胺反应。京尼平进入纤维蛋白凝胶的反应速率通过光谱学测量，而边缘交联形成的速率通过流变学测量。纤维蛋白凝胶中京尼平和伯胺之间的共价偶联在京尼平浓度下服从二级动力学，有效活化能为-71.9 +/- 3.2 kJ mol（-1）。京尼平在纤维蛋白凝胶内的扩散反应表现出0.02-0.28之间的Thiele模量，这表明本文研究的系统是反应限制的。京尼平交联的纤维蛋白凝块对纤维蛋白溶解降解具有抗性，如通过流变学测量的。最后，活性京尼平可以从聚（D，L-丙交酯-共-乙交酯）基质以与掺入纤维蛋白网络的特征速率相当的速率递送至凝胶。总之，这项工作建立了一个定量的框架，工程控制释放系统的京尼平交付到蛋白质为基础的水凝胶网络。
Genipin is a naturally derived small molecule that crosslinks compounds containing primary amines including many natural biopolymers. A diffusion-reaction model to predict the rates of delivery and incorporation of genipin into fibrin networks is presented. Genipin crosslink formation within fibrin hydrogels is a multi-step process that requires genipin diffusion and reaction with primary amines in hydrated networks. The reaction rate of genipin into fibrin gels was measured via spectroscopy while the rate of marginal crosslink formation was measured by rheology. Covalent coupling between genipin and primary amines in fibrin gels obeys second-order kinetics in genipin concentration with an effective activation energy of -71.9 +/- 3.2 kJ mol(-1). Genipin diffusion-reaction within fibrin gels exhibits Thiele moduli between 0.02-0.28, which suggests that the systems studied herein are reaction-limited. Genipin-crosslinked fibrin clots are resistant to fibrinolytic degradation as measured by rheology. Finally, active genipin can be delivered from poly(D,L-lactide-co-glycolide) matrices to gels at rates that are comparable to the characteristic rate of incorporation in fibrin networks. Taken together, this work establishes a quantitative framework to engineer controlled release systems for genipin delivery into protein-based hydrogel networks.