Controlled release of tethered molecules via engineered hydrogel degradation: Model development and validation
Controlled release of tethered molecules via engineered hydrogel degradation: Model development and validation
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DOI：
10.1002/jbm.a.30307
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发表时间：
2005-07-01
影响因子：
4.9
通讯作者：
Metters, AT
中科院分区：
文献类型：
--
作者：
DuBose, JW;Cutshall, C;Metters, AT
已经开发了一个动力学共动力学模型来预测水解或酶促降解对通过迈克尔型加成反应形成的水凝胶的宏观性质的影响。占的理论计算的重要参数是键断裂动力学，微观结构的网络特性，如大分子单体的功能和交联效率，和降解产物的详细分析。以前的工作表明，这种建模方法的有效性预测溶胀行为的水解降解凝胶在降解的早期阶段和定量依赖的动力学和结构参数的凝胶降解。理论方法在目前的工作中扩展到预测释放共价结合的蛋白质从网络通过不稳定的债券。网络结合的荧光探针的释放研究允许模型降解参数的验证，并表明大分子单体官能化和网络交联效率可以适当地定制，以实现所需的溶胀曲线和蛋白质释放速率在可降解凝胶的寿命。这些网络参数的凝胶溶解的时间和蛋白质的释放，发生在这一阶段的降解的影响也被确定，突出的效用开发的模型作为一个全面的工具，用于优化可降解的水凝胶作为药物输送和组织再生的矩阵。(c)2005 Wiley Periodicals，Inc. J Biomed Mater Res 74A：104-116，2005.
A statistical-co-kinetic model has been developed to predict effects of hydrolytic or enzymatic degradation on the macroscopic properties of hydrogels formed through Michael-type addition reactions. Important parameters accounted for by the theoretical calculations are bond cleavage kinetics, microstructural network characteristics such as macromer functionality and crosslinking efficiency, and detailed analysis of degradation products. Previous work indicated the validity of this modeling approach for predicting swelling behavior of hydrolytically degradable gels during early stages of degradation and the quantitative dependence of gel degradation on kinetic and structural parameters. The theoretical methodology is extended in the current work to predict release of covalently bound proteins from the network via labile bonds. Release studies of a network-bound fluoroscopic probe allow validation of model degradation parameters and indicate that macromer functionalization and network crosslinking efficiency can be appropriately tailored to achieve desired swelling profiles and protein release rates over the lifetime of the degradable gel. The effects of these network parameters on the timing of gel dissolution and the protein release that occurs during this phase of degradation are also identified, highlighting the utility of the developed model as a comprehensive tool for optimizing degradable hydrogels as matrices for drug delivery and tissue regeneration. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res 74A: 104-116, 2005.