Lin Chien-Chi, Metters Andrew T, Anseth Kristi S
Department of Chemical and Biological Engineering, University of Colorado, 424 UCB, Boulder, CO 80309, USA.
Biomaterials. 2009 Oct;30(28):4907-14. doi: 10.1016/j.biomaterials.2009.05.083. Epub 2009 Jun 27.
Hydrogels are an important class of biomaterials for cell encapsulation and delivery, providing a physical barrier or "immuno-isolation" between the host tissue and encapsulated cells. The semi-permeable gel protects the encapsulated cells from host immune cells and/or antibody recognition while allowing facile diffusion of nutrients. However, a previously un-addressed problem is that highly permissive hydrogels cannot exclude the infiltration of soluble immune-mediators, such as pro-inflammatory cytokines that are highly expressed in wounded environments in vivo. When encountered with pro-inflammatory cytokines, encapsulated cells fail to perform their desired functions. Here, we report the synthesis, characterization, and application of peptide-functionalized, cytokine-antagonizing poly(ethylene glycol) (PEG) hydrogels capable of sequestering the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFalpha). Results demonstrate that the survival, function, and differentiation of encapsulated cells (e.g., rat adrenal pheochromocytoma cells--PC12s, mouse pancreatic islets, and human mesenchymal stem cells or hMSCs) are significantly hindered in un-modified PEG hydrogels under in vitro TNFalpha treatments. In contrast, cells encapsulated in TNFalpha-antagonizing hydrogels are un-affected by the infiltrated TNFalpha. This study demonstrates the importance of controlling the availability of pro-inflammatory cytokines in highly permissive hydrogels.
水凝胶是用于细胞封装和递送的一类重要生物材料，可在宿主组织与封装细胞之间提供物理屏障或“免疫隔离”。这种半透性凝胶可保护封装细胞免受宿主免疫细胞和/或抗体识别，同时允许营养物质轻松扩散。然而，一个以前未解决的问题是，高渗透性水凝胶无法排除可溶性免疫介质的渗入，例如在体内伤口环境中高表达的促炎细胞因子。当遇到促炎细胞因子时，封装细胞无法发挥其预期功能。在此，我们报告了能够螯合促炎细胞因子肿瘤坏死因子α（TNFα）的肽功能化、细胞因子拮抗聚乙二醇（PEG）水凝胶的合成、表征及应用。结果表明，在体外TNFα处理下，未修饰的PEG水凝胶中封装细胞（如大鼠肾上腺嗜铬细胞瘤细胞——PC12、小鼠胰岛和人间充质干细胞或hMSC）的存活、功能及分化受到显著阻碍。相比之下，封装在TNFα拮抗水凝胶中的细胞不受渗入的TNFα影响。本研究证明了在高渗透性水凝胶中控制促炎细胞因子可用性的重要性。
