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通过巯基-马来酰亚胺迈克尔加成原位形成聚(乙二醇)基水凝胶。

In situ forming poly(ethylene glycol)-based hydrogels via thiol-maleimide Michael-type addition.

机构信息

School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, USA.

出版信息

J Biomed Mater Res A. 2011 Aug;98(2):201-11. doi: 10.1002/jbm.a.33106. Epub 2011 May 4.

Abstract

The incorporation of cells and sensitive compounds can be better facilitated without the presence of UV or other energy sources that are common in the formation of biomedical hydrogels such as poly(ethylene glycol) hydrogels. The formation of hydrogels by the step-growth polymerization of maleimide- and thiol-terminated poly(ethylene glycol) macromers via Michael-type addition is described. The effects of macromer concentration, pH, temperature, and the presence of biomolecule gelatin on gel formation were investigated. Reaction kinetics between maleimide and thiol functional groups were found to be rapid. Molecular weight increase over time was characterized via gel permeation chromatography during step-growth polymerization. Swelling and degradation results showed incorporating gelatin enhanced swelling and accelerated degradation. Increasing gelatin content resulted in the decreased storage modulus (G'). The in vitro release kinetics of fluorescein isothiocyanate (FITC)-labeled dextran from the resulting matrices demonstrated the potential in the development of novel in situ gel-forming drug delivery systems. Moreover, the resulting networks were minimally adhesive to primary human monocytes, fibroblasts, and keratinocytes thus providing an ideal platform for further biofunctionalizations to direct specific biological response.

摘要

在不存在常见于生物医学水凝胶(如聚乙二醇水凝胶)形成过程中的 UV 或其他能源的情况下,可以更好地促进细胞和敏感化合物的掺入。本文描述了马来酰亚胺和巯基封端的聚乙二醇大分子单体通过迈克尔加成逐步聚合形成水凝胶的过程。考察了大分子单体浓度、pH 值、温度以及生物分子明胶的存在对凝胶形成的影响。发现马来酰亚胺和巯基官能团之间的反应动力学很快。在逐步聚合过程中通过凝胶渗透色谱法对随时间的分子量增加进行了表征。溶胀和降解结果表明,明胶的掺入增强了溶胀并加速了降解。增加明胶含量会导致储能模量 (G') 降低。从所得基质中释放荧光素异硫氰酸酯 (FITC) 标记的葡聚糖的体外释放动力学表明,有可能开发新型原位凝胶形成药物递送系统。此外,所得网络对原代人单核细胞、成纤维细胞和角质形成细胞的黏附性最小,因此为进一步的生物功能化提供了理想的平台,以指导特定的生物学反应。

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