Strain-stiffening Hydrogels with Dynamic, Secondary Crosslinking

Hydrogels are water-swollen, typically soft networks useful as biomaterials and in other fields of biotechnology. Hydrogel networks capable of sensing and responding to external perturbations, such as light, temperature, pH, or force, are useful across a wide range of applications requiring on-demand crosslinking or dynamic changes. Thus far, although mechanophores have been widely described as strain-sensitive reactive groups, embedding this type of force-responsiveness into hydrogels is unproven. Here, we synthesized multi-functional polymers that combine a hydrophilic zwitterion with strong, permanently crosslinking alkenes and dynamically crosslinking dithiols. From these polymers, we created hydrogels that contained irreversible and strong thiol-ene crosslinks and reversible dithiol crosslinks, and they stiffened in response to strain, increasing hundreds of kPa in modulus under compression. We examined variations in polymer composition and used a constitutive model to determine how to balance the number of thiol-ene vs. dithiol crosslinks to create maximally force-responsive networks. These strain-stiffening hydrogels represent potential biomaterials that benefit from the mechano-responsive behavior needed for emerging applications in areas such as tissue engineering