Student: Nan Wu
Project: Microrheological characterization of covalent adaptable hydrogel degradation in response to temporal pH changes that mimic the gastrointestinal tract
View: Research Poster (PDF) | Presentation (YouTube)
Department: Chemical and Biomolecular Engineering
Advisor: Kelly Schultz
Abstract
Dynamic covalent chemistry is used in polymer scaffold design to create covalent adaptable hydrogel (CAHs). These materials enable dynamic rearrange of the material structure in response to various stimuli, including cues that the material could experience in the body such as pH changes in the gastrointestinal (GI) tract. Stimuli-induced structural evolution expands the use of CAHs for biological applications, including as an oral drug delivery vehicle. To design CAHs as vehicles for controlled and targeted oral delivery, scaffold degradation in response to changes in pH that mimic the both the pH and time in each organ in the GI tract must be characterized. We focus on characterization of the degradation of a CAH scaffold which is composed of 8-arm star poly(ethylene glycol) (PEG)-hydrazine that self-assembles with 8-arm star PEG-aldehyde, forming covalent adaptable hydrazone bonds. To precisely characterize material rheology and degradation mechanism of this CAH in response to pH changes, we use a unique experimental platform μ2rheology, microrheology in a microfluidic device. This technique enables the design of experiments that mimic the native pH environment in the GI tract. We use passive microrheology, specifically multiple particle tracking microrheology (MPT), to characterize CAH degradation. In MPT, fluorescently labeled probe particles are embedded in the material and their Brownian motion is measured to extract rheological properties. Our two-layer microfluidic device enables consecutive fluid exchange around a single sample with minimal sample loss. Using μ2rheology, we characterize degradation at a single pH (pH 4.3, 5.5 and 7.4), consecutive degradation with a single pH exchange (pH 4.3 to 7.4 and pH 7.4 to 4.3) and temporal pH changes that mimic the pH in the entire GI tract. We quantify the gel-point during degradation by calculating the critical relaxation exponent, which is independent of degradation pH. In addition, we report that degradation kinetics and material property evolution are not impacted by degradation history. However, the initial cross-link density of the scaffold at each pH exchange can be decreased by degradation history which reduces the time 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. This work also shows the utility of μ2rheology in characterization and, subsequently, design of new dynamic materials for targeted drug delivery.
About Nan Wu
Nan Wu is currently a final year graduate student in CHBE at Lehigh. Her work has focused on the rheology of emerging biomaterials includes covalent adaptable networks and enzymatically degradable scaffolds for design and engineering of controlled, targeted drug delivery vehicles.