Stimuli-Responsive Hydrogels from Dynamic Network Interactions

Hydrogels are hydrated 3-dimensional networks of polymer chains. The polymer chains are connected by crosslinks, which may be covalent bonds or physical network junctions based on non-covalent intermolecular interactions. While covalent crosslinks give hydrogels advantageous mechanical properties such as high stiffness and strength, these bonds translate to static networks which are unable to respond to environmental stimuli. In contrast, dynamic or non-covalent crosslinks endow hydrogels with the ability to respond to environmental cues. Stimuli-responsive hydrogels are of interest for a large range of applications, many of which are bioinspired, with the goal of emulating the rapid and complex natural responses of living organisms to their environments. These include sensors based on mechanoresponsive strain-stiffening or mechanochromic hydrogels, shear-thinning and self- healing hydrogels for 3D printing, wound dressings, and injectable therapeutics, and chemoresponsive hydrogels for controlled release and delivery of therapeutics. Here, dynamic and non-covalent crosslinking motifs are utilized to develop hydrogel-based materials which exhibit tunable stimuli-responsive behaviors. First, the strain-responsive stiffening of 4-arm poly(ethylene glycol) hydrogels crosslinked with dynamic-covalent boronate esters is explored. This system allows the impact of dynamic-covalent crosslinking on strain-stiffening to be studied without additional polymer chain interactions. The magnitude of the strain-stiffening response increases with decreasing crosslink density and gel stiffness. A cellulose-based hydrogel system is characterized next, which incorporates both dynamic-covalent and hydrogen bonding motifs. The contributions of these interactions to various mechanoresponsive behaviors, including strain-stiffening and shear-thickening, are studied. To further explore the impact of dynamic interactions on hydrogel strain-stiffening, the behaviors of covalent and dynamic-covalent hydrogels in response to mechanical stimuli are compared. This work reveals that dynamic crosslinking is essential for strain-stiffening in synthetic hydrogel systems, and in fact, the magnitude of the strain-stiffening response is well- correlated with the reverse rate constant of the crosslinking reaction. Lastly, a chemoresponsive hydrogel capsule system is designed based on dynamic-covalent crosslinking and electrostatic interactions. Enzymatic activity enabled glucose-responsive dissolution. This work highlights the importance of dynamic crosslinking motifs in engineering stimuli- responsive hydrogel materials. These findings have provided design insight towards realizing biomimetic materials with tunable stimuli-responsive properties.