Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
Acta Biomater. 2010 Apr;6(4):1307-18. doi: 10.1016/j.actbio.2009.11.027. Epub 2009 Nov 23.
The dimensional stability and rheological properties of a series of comb-like copolymers of N-isopropyl acrylamide (NIPAAm) and methoxy poly(ethylene glycol) methacrylate (mPEGMA), poly(NIPAAm-co-mPEGMA), with varying poly(ethylene glycol) (PEG) graft densities and molecular weights were studied. The thermoresponsive character of the copolymer solutions was investigated by kinetic and equilibrium swelling, as well as by static and dynamic mechanical analysis. Surface response mapping was employed to target particular compositions and concentrations with excellent dimensional stability and a relatively large change in dynamic mechanical properties upon thermoreversible gelation. The mechanical characteristics of the gels depended strongly upon concentration of total polymer and less so upon copolymer ratio. Increased PEG graft density was shown to slow the deswelling rate and increase the equilibrium water content of the gels. Upon gelation at sol concentrations of 1-20 wt.% the materials underwent no deswelling or syneresis and maintained stable gels with a large elastic regime and high yield strain (i.e. elastic and soft but tough), even within the Pascal range of complex shear moduli. These materials are unique in that they maintained a physiologically useful lower critical solution temperature (approximately 33 degrees C), despite having a high PEG content. Copolymers with a high PEG content and low polymer fraction were conveniently transparent in the gel phase, allowing visualization of cellular activity without disrupting the microenvironment. Mesenchymal stem cells showed good viability and proliferation in three-dimensional culture within the gels, despite the lack of ligand incorporation to promote cellular interaction. Multi-component matrices can be created through simple mixing of copolymer solutions and peptide-conjugated linear polymers and proteins to produce combinatorial microenvironments with the potential for use in cell biology, tissue engineering and medical applications.
研究了一系列具有不同聚乙二醇（PEG）接枝密度和分子量的 N-异丙基丙烯酰胺（NIPAAm）和甲氧基聚乙二醇甲基丙烯酸酯（mPEGMA）梳状共聚物，聚（NIPAAm-co-mPEGMA）的尺寸稳定性和流变性能。通过动力学和平衡溶胀以及静态和动态力学分析研究了共聚物溶液的热响应特性。采用表面响应映射技术，针对特定组成和浓度，目标是具有优异尺寸稳定性和相对较大的动态力学性能变化的共凝胶。凝胶的力学特性强烈依赖于总聚合物的浓度，而对共聚物比例的依赖性较小。增加 PEG 接枝密度会降低凝胶的溶胀速率并增加凝胶的平衡含水量。在溶胶浓度为 1-20wt.%下凝胶化时，这些材料不会发生溶胀或收缩，并且即使在复杂剪切模量的帕斯卡范围内，仍保持具有大弹性区和高屈服应变（即弹性和柔软但坚韧）的稳定凝胶。这些材料的独特之处在于，尽管具有高 PEG 含量，但它们仍保持了有用的生理下限临界溶液温度（约 33 摄氏度）。具有高 PEG 含量和低聚合物分数的共聚物在凝胶相中方便地是透明的，允许在不破坏微环境的情况下可视化细胞活性。间充质干细胞在凝胶内的三维培养中表现出良好的活力和增殖能力，尽管没有加入配体以促进细胞相互作用。通过简单混合共聚物溶液和肽缀合的线性聚合物和蛋白质，可以创建多组分基质，从而产生具有用于细胞生物学、组织工程和医学应用潜力的组合微环境。
