Significance
Various strategies to tune hydrogel mechanics have been developed to control human mesenchymal stem cell (hMSC) behavior and regulate their immunomodulatory potential. However, these strategies typically couple mechanics to network connectivity, which in turn changes other hydrogel properties such as permeability that may have unintended effects on hMSC behavior. This work presents a strategy to tune hydrogel mechanics using crosslinkers with different secondary structure and molecular rigidity. This strategy successfully decouples hydrogel moduli from crosslinker stoichiometry and mimics the hierarchical nature of the native extracellular matrix. The moduli of the developed hydrogels led to significant impacts on hMSC morphology and proliferation, and increased immunomodulatory potential, indicating that molecular rigidity is a promising avenue to control engineered ECM mechanics for therapeutic applications.
Statement of significance
Various strategies to tune hydrogel mechanics have been developed to control human mesenchymal stem cell (hMSC) behavior and regulate their immunomodulatory potential. However, these strategies typically couple mechanics to network connectivity, which in turn changes other hydrogel properties such as permeability that may have unintended effects on hMSC behavior. This work presents a strategy to tune hydrogel mechanics using crosslinkers with different secondary structure and molecular rigidity. This strategy successfully decouples hydrogel moduli from crosslinker stoichiometry and mimics the hierarchical nature of the native extracellular matrix. The moduli of the developed hydrogels led to significant impacts on hMSC morphology and proliferation, and increased immunomodulatory potential, indicating that molecular rigidity is a promising avenue to control engineered ECM mechanics for therapeutic applications.