Stretch activated molecule immobilization in disulfide linked double network hydrogels

Inspired by how forces facilitate molecule immobilization in biological tissues to provide localized functionalization, tough hydrogel networks with stretch activated mechanochemistry are developed by utilizing disulfide bonds as dynamic covalent crosslinks. Specifically, disulfide linked polyethylene glycol hydrogels are reinforced with a second ionically bonded sodium alginate network to simultaneously achieve stretchability and mechanochemical functionalization. To demonstrate and quantify the mechanochemical response, thiols produced by disulfide bond rupture are sensed during stretching using a reaction activated fluorophore dissolved in the hydrating solution. By monitoring the increase in fluorescence intensity upon stretching, it is determined that disulfide bond breakage in the double network hydrogels becomes more activated in hydrogels with high stretchability under low stress. Such results provide guidance regarding how the molecular weights and mass fractions of the monomers must be chosen to design double network hydrogels that balance favorable mechanical properties and mechanochemical responsiveness. Finally, for the most mechanochemically active hydrogel, we demonstrate how the stretch-activated immobilization of a maleimide containing peptide can functionalize the gels to promote the growth of human fibroblasts. Results of this work are anticipated to encourage further research into the development of stretchable and multifunctionalizable hydrogels for biotechnology and biomedical applications. STATEMENT OF SIGNIFICANCE: Inspired by the mechanochemical dynamics in biological tissues, this work demonstrates the development of hydrogel-based biomaterials that can achieve stretch activated functionalization by molecule immobilization in multiple distinct ways. Using disulfide linked polyethylene glycol hydrogels reinforced with a second alginate network, we have elucidated the structure-property relationships of our hydrogels by functionalizing them with fluorophore to ensure a robust combination of stretchability and mechanochemical responsiveness. We also have demonstrated the capability for using stretch activated immobilization of functional peptides to guide human fibroblasts activity. By demonstrating how hydrogel network properties impact both mechanical and functional performance, this work opens pathways for designing multifunctionalizable hydrogels that adapt to mechanical forces, potentially broadening the application of hydrogels in biotechnology and biomedical applications.