Bioactive Hydrogels with Enhanced Initial and Sustained Cell Interactions
Bioactive Hydrogels with Enhanced Initial and Sustained Cell Interactions
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DOI：
10.1021/bm400634j
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发表时间：
2013-07-01
影响因子：
6.2
通讯作者：
Cosgriff-Hernandez, Elizabeth M.
中科院分区：
文献类型：
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作者：
Browning, Mary Beth;Russell, Brooke;Cosgriff-Hernandez, Elizabeth M.
聚乙二醇基水凝胶体系的高度可调性使其可用于广泛的再生医学和药物输送应用。聚乙二醇水凝胶最有价值的特性之一是其对蛋白质吸附和细胞黏附的固有抵抗力，因为它允许可控地引入所需的生物活性因子，包括蛋白质、多肽和药物。丙烯酸酯-聚乙二醇N-羟基丁二酰亚胺(ACR-PEG-NHS)作为聚乙二醇键联剂被广泛应用于生物活性因子的光交联基功能化。这使得它们能够方便地并入聚乙二醇水凝胶网络或使用聚乙二醇化策略进行药物输送。然而，聚乙二醇联接物可以立体地阻断功能化蛋白质上的整合素结合部位，并减少细胞与材料的相互作用。在这项研究中，我们证明了在功能化过程中降低蛋白质骨架上的聚乙二醇键密度可以显著改善细胞的粘附性和向生物活性水凝胶的扩散。然而，这种官能化密度的降低也会随着时间的推移增加基质中的蛋白质损失，这是由于ACR-PEG-NHS连接体的酯水解性造成的。为了解决这一问题，合成了一种新型的聚乙二醇键联剂丙烯酰胺-聚乙二醇异氰酸酯(AAM-PEGI)，提高了其水解性。研究发现，降低AAM-PEG-I的官能化密度会导致细胞黏附和扩散到ACR-PEG-NHS系统的相应增加，同时在显著更长的时间框架内保持水凝胶网络中的蛋白质和生物活性水平。因此，AAM-PEG-I为蛋白质功能化提供了一种新的选择，可用于广泛的应用，改善初始和持续的细胞-材料相互作用，以增强对生物活性的控制。
The highly tunable properties of poly(ethylene glycol) (PEG)-based hydrogel systems permit their use in a wide array of regenerative medicine and drug delivery applications. One of the most valuable properties of PEG hydrogels is their intrinsic resistance to protein adsorption and cell adhesion, as it allows for a controlled introduction of desired bioactive factors including proteins, peptides, and drugs. Acrylate-PEG-N-hydroxysuccinimide (Acr-PEG-NHS) is widely utilized as a PEG linker to functionalize bioactive factors with photo-cross-linkable groups. This enables their facile incorporation into PEG hydrogel networks or the use of PEGylation strategies for drug delivery. However, PEG linkers can sterically block integrin binding sites on functionalized proteins and reduce cell-material interactions. In this study we demonstrate that reducing the density of PEG linkers on protein backbones during functionalization results in significantly improved cell adhesion and spreading to bioactive hydrogels. However, this reduction in functionalization density also increases protein loss from the matrix over time due to ester hydrolysis of the Acr-PEG-NHS linkers. To address this, a novel PEG linker, acrylamide-PEG-isocyanate (Aam-PEG-I), with enhanced hydrolytic stability was synthesized. It was found that decreasing functionalization density with Aam-PEG-I resulted in comparable increases in cell adhesion and spreading to Acr-PEG-NHS systems while maintaining protein and bioactivity levels within the hydrogel network over a significantly longer time frame. Thus, Aam-PEG-I provides a new option for protein functionalization for use in a wide range of applications that improves initial and sustained cell-material interactions to enhance control of bioactivity.