Microrheological characterization of covalent adaptable hydrogel degradation in response to temporal pH changes that mimic the gastrointestinal tract

Abstract

Covalent adaptable hydrogels (CAHs) reversibly adapt their structure in response to external stimuli, emerging as a new platform for biological applications. Due to the unique and complex nature of these materials, a characterization technique is needed to measure the rheology of these CAHs in biological processes. μ²rheology, microrheology in a microfluidic device, is a technique that can fully characterize real-time CAH degradation in a changing environment, such as the pH environment of the GI tract. This characterization will enable design and tailoring of these materials for controlled and targeted oral drug delivery. Using μ²rheology, we can exchange the fluid environment without sample loss and measure the change in CAH rheological properties. We show degradation kinetics and material property evolution are independent of degradation history. However, the initial cross-link density at each pH exchange can be decreased by degradation history which decreases the time for the CAH to degrade to the gel–sol transition. These results indicate that CAH degradation can be tuned by changing the initial material properties by varying polymer concentration and ratio of functional groups. We also show that μ²rheology will enable the design of new dynamic materials for targeted drug delivery by enabling these materials to be characterized and tailored in vitro.