Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Biomaterials. 2010 Jun;31(18):4864-71. doi: 10.1016/j.biomaterials.2010.02.059. Epub 2010 Mar 26.
Hydrogels are increasingly used as a cell encapsulation and transplantation device. The successful use of a hydrogel greatly relies on an ability to control hydrogel stiffness which affects structural integrity and regulates cellular phenotypes. However, conventional strategies to increase the gel stiffness lead to decrease in the gel permeability and subsequently deteriorate the viability of cells encapsulated in a gel matrix. This study presents a strategy to decouple the inversed dependency of permeability on the stiffness of a hydrogel by chemically cross-linking methacrylic alginate with poly(ethylene glycol) dimethacrylate (PEGDA). As expected, gel stiffness represented by elastic modulus was tuned over one order of magnitude with the concentration of methacrylic alginate and the degree of substitution of methacrylic groups. In contrast, swelling ratio of the hydrogel indicative of gel permeability was minimally changed because of multiple hydrophilic groups of alginate, similar to function of proteoglycans in a natural extracellular matrix. Furthermore, viability of neural cells encapsulated in a hydrogel of PEGDA and methacrylic alginate rather increased with hydrogel stiffness. Overall, the results of this study demonstrate an advanced biomaterial design paradigm which allows one to culture cells in a 3D matrix of varying rigidity. This study will therefore greatly expedite the use of a hydrogel system in both fundamental studies and clinical settings of cell therapies.
水凝胶作为一种细胞包封和移植的装置，应用越来越广泛。水凝胶的成功应用在很大程度上依赖于控制水凝胶硬度的能力，而水凝胶硬度影响结构完整性并调节细胞表型。然而，提高凝胶硬度的传统策略会导致凝胶渗透性降低，从而损害凝胶基质中包封细胞的活力。本研究提出了一种通过化学交联甲基丙烯酰化藻酸盐与聚乙二醇二甲基丙烯酸酯（PEGDA）来解耦水凝胶渗透性与硬度之间的反比依赖性的策略。正如预期的那样，通过甲基丙烯酰化藻酸盐的浓度和甲基丙烯酰基团的取代度来调节凝胶的弹性模量，从而在一个数量级上调节凝胶的硬度。相比之下，由于藻酸盐的多个亲水基团，类似于天然细胞外基质中蛋白聚糖的功能，水凝胶的溶胀比（指示凝胶渗透性）的变化极小。此外，包封在聚乙二醇二甲基丙烯酸酯和甲基丙烯酰化藻酸盐水凝胶中的神经细胞的活力随着水凝胶硬度的增加而增加。总的来说，这项研究的结果展示了一种先进的生物材料设计范例，允许在不同刚性的 3D 基质中培养细胞。因此，这项研究将极大地促进水凝胶系统在细胞治疗的基础研究和临床应用中的使用。
