Tuning the dependency between stiffness and permeability of a cell encapsulating hydrogel with hydrophilic pendant chains

Abstract

The mechanical stiffness of a hydrogel plays a significant role in regulating the phenotype of cells that adhere to its surface. However, the effect of hydrogel stiffness on cells cultured within its matrix is not well understood, because of the intrinsic inverse dependency between the permeability and stiffness of hydrogels. This study therefore presents an advanced biomaterial design strategy to decrease the inverse dependency between permeability and stiffness of a cell encapsulating hydrogel. Hydrogels were made by cross-linking poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) monoacrylate (PEGMA), with PEGMA acting as a pendant polymer chain. Increasing the mass fraction of PEGMA while keeping the total polymer concentration constant led to a decrease in the elastic modulus (E) of the hydrogel, but caused a minimal increase in the swelling ratio (Q). The size and hydrophobicity of the end groups of pendant PEG chains further fine tuned the dependency between Q and E of the hydrogel. Pure PEGDA hydrogels with varying molecular weights, which show the same range of E but a much greater range of Q, were used as a control. Fibroblasts encapsulated in PEGDA-PEGMA hydrogels displayed more significant biphasic dependencies of cell viability and vascular endothelial growth factor (VEGF) expression on E than those encapsulated in pure PEGDA hydrogels, which were greatly influenced by Q. Overall, the hydrogel design strategy presented in this study will be highly useful to better regulate the phenotype and ultimately improve the therapeutic efficacy of a wide array of cells used in various biology studies and clinical settings.