(33g) Covalent Adaptable Hydrogel Networks for Delivery during Digestion

Covalent adaptable hydrogels (CAHs) are attractive biomaterials due to their ability to break and reform bonds in response to external stimuli. Although there are many new CAHs described in the literature, these materials are often characterized using bulk rheology and a classic stress relaxation experiment. This experiment determines whether the scaffold returns to equilibrium properties after bond degradation due to an applied external stress. This information is extraordinarily useful, but does not describe how the material will react to subtle changes in the environment, like changes in pH during digestion. We characterize dynamic changes in a CAH in response to changes in pH in the incubation environment. The CAH we are characterizing is composed of 8-arm star poly(ethylene glycol)(PEG)-hydrazine that self-assembles with an 8-arm star PEG-aldehyde creating a covalent adaptable hydrazone bond. Previous work used multiple particle tracking microrheology (MPT) to characterize this scaffold when the incubation pH is changed. In MPT, fluorescently labeled probe particles are embedded in the material and their Brownian motion is captured using video microscopy. This particle movement is related to rheological properties, such as the creep compliance, using the Generalized Stokes-Einstein Relation. In our previous work, we determined that scaffold degradation at an acidic pH occurred rapidly and was followed by spontaneously gelation without any added stimuli. At physiological pH, we measured fast degradation to the gel-sol transition and then the scaffold oscillated between the gel and sol until complete degradation after 10 days. To mimic changes in pH that occur during digestion we know characterize CAH degradation using μ²rheology. μ²rheology is MPT in a microfluidic device. Our device enables changes in the fluid environment around the hydrogel sample. In these measurements we change between acidic and physiological conditions, a change in pH found in the digestive track. We determine that degradation at pH 7 is accelerated when the CAH is first degraded at pH 4. There is no change in degradation when the material is first degradation at pH 7 and then at pH 4. This new technique will mimic the temporal pH changes during digestion to determine the degradation of this CAH and, in future work, the ability to release molecules from the scaffold throughout the entire process.