Hydrogels are extensively studied and engineered for use in many commercial products including sensors, membranes, drug delivery devices and synthetic extracellular matrices. The further success of hydrogels in commercial applications relies on the ability to control several physical properties in an independent manner. However, current hydrogel designs often encounter difficulty in the independent control of mechanics and permeability. For example, efforts to make a softer hydrogel often encounter the significant increase of the swelling ratio of the hydrogel, thus leading to undesirable disruption of micro-scale patterns and porous architecture. This inverse dependency between hydrogel mechanics and transport can cause significant limitations to hydrogel functionality.
In this study, we hypothesized that the chain inflexibility of a polymeric cross-linker is an important factor to tune the dependency between stiffness and permeability of a hydrogel. This hypothesis was examined using polymeric cross-linkers, which had a sugar-based backbone (alginate) or an alkyl chain backbone (acrylic acid), to represent various degrees of chain flexibility. These polymers were modified with varying degrees of substitution of methacrylic groups to control the number of cross-links of the hydrogel. Interestingly, the poly(acrylamide) hydrogels cross-linked by the more inflexible alginate methacrylates exhibited the significantly less dependency between swelling ratio and elastic modulus than those cross-linked by the flexible poly(acrylic acid) methacrylates. The critical role of these cross-linkers in mediating the mechanical and permeation properties of the hydrogel were further related to the ability of the cross-linkers to self-organize, by using a pyrene assay. Finally, the hydrogel cross-linked by alginate methacrylates maintained its pre-defined micropatterns of cell adhesion proteins independent of the hydrogel stiffness, such that the cells could respond to solely the substrate mechanics and not to changes in swelling of the hydrogel. Overall, the results of this study serve to advance the controllability of hydrogel properties, in order to greatly enhance the function and performance of the hydrogels in various applications.