(651g) Tuning the Dependency Between Stiffness and Permeability of Cell-Encapsulating Hydrogel with Hydrophilic Pendant Chains

Hydrogels are widely used as a platform to study the effect of mechanical stiffness of extracellular matrix (ECM) on various cellular phenotypes.  However, using hydrogel to explore the role of ECM stiffness in three dimensions (3D) has been a great challenge, since conventional hydrogel systems rely on cross-linking density to control the stiffness, which inevitably affects permeability, thus masking the sole effect of mechanical stiffness in 3D.  This study therefore presents an advanced hydrogel design strategy to decrease the inverse dependency between permeability and stiffness of a cell-encapsulating hydrogel by introducing pendant polymer chains.  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.  The 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 control the mechanical environment in a refined manner to regulate various phenotypes of the encapsulated cells, and ultimately improve therapeutic efficacy of a wide array of cells used in biomedical applications.