(218a) Correlation of Dynamic Scaffold Rheology with Molecular Release during Material Degradation

Hydrogel scaffolds are designed to be delivery vehicles for drugs and nutrients, but measuring deliver during material degradation has been a challenge. The goal of this work is to establish a quantitative correlation between molecular release and material degradation. We characterize a radical-initiated photopolymerized hydrogel and a base-initiated Michael addition polymerized hydrogel. These gels are chosen because they form networks through distinct cross-linking reactions. Both scaffolds have the same poly(ethylene glycol) (PEG) backbone and are cross-linked with the same degradable peptide, which enables degradation through the same enzymatic degradation reaction. A fluorescently labeled PEG molecule is chemically conjugated to the scaffold and is released during enzymatic degradation. Real-time changes in scaffold rheological properties during degradation are measured using bulk rheology. Molecular release is measured by quantifying the fluorescence in the incubation liquid and the hydrogel scaffold. A complicating factor, described in the literature, is that shear may cause increased cross-linking after initiation of degradation resulting in an increase in storage modulus, which would change release profiles. We test the hypothesis that shear induces additional cross-linking in degrading hydrogel scaffolds. To do this, enzymatic degradation is characterized using bulk rheology as materials undergo continuous or minimal shear and molecular release is measured when the material is incubated with and without shaking. We determine that shear does not change scaffold degradation or release regardless of gelation reaction. Instead, the type of hydrogel cross-linking reaction greatly affects both material degradation and molecular release. Hydrogel cross-linked by base-initiated Michael addition undergo further cross-linking at the start of degradation, which results in minimal release. This is due to the swelling of the material enabling unreacted arms to form new chemical cross-links. We correlate release with enzymatic degradation for both scaffolds. We determine that material storage modulus is indirectly correlated with release during degradation. These results indicate that rheological characterization is a useful tool to characterize and predict the release of molecules from degrading hydrogels.