Investigating the stimuli responsiveness of reversible thia-conjugate addition crosslinked hydrogels

Dynamic hydrogels have recently demonstrated utility as versatile biomaterials. Characterized by the spontaneous rearrangement of crosslinks at ambient conditions, dynamic hydrogels more closely mimic the native extracellular matrix better than their static hydrogel counterparts, and the wide parameter space allows for a high degree of control for drug release applications. Despite the promising applicability that these hydrogels demonstrate, the structure-property relationships that govern the effects of the hydrogel composition on the mechanics remain poorly understood. An ideal system for investigating both the relationship of crosslinking on hydrogel mechanics in addition to biomaterial applications are hydrogels crosslinked through reversible covalent crosslinks. A number of reversible covalent bonds have well defined mechanisms that allow for facile determination of their rate constants via kinetic model fitting. Oscillatory rheometry also provides a robust mechanical method to characterize both the overall stiffness and dynamics of the dynamic hydrogels. In order to investigate the structure-property relationships in reversible covalently crosslinked hydrogels, this work first incorporated a reversible thia-conjugate addition reaction into a hydrogel. Previous small molecule research established this reaction as a reversible covalent reaction under standard biological conditions, and the first part of this project functionalized macromers and analyzed how chemical changes to the functional groups influenced the kinetics and mechanics of the resulting hydrogel. The accepted mechanism of this reaction reveals a deprotonation step in the forward and reverse direction which lead to the second area of research, wherein pH values from 3 to 7 were used to alter the kinetics and mechanics of a reversible thia-conjugate addition crosslinked hydrogels. Additionally, a gastrointestinal molecular release study was performed to demonstrate the drug delivery applications of this hydrogel. Finally, the temperature dependence of the crosslinking reaction was analyzed, and reaction parameters were determined from the mechanical analysis. In summary, three stimuli; chemistry, pH, and temperature, were used to investigate the structure-property relationships in reversible thia-conjugate addition crosslinked hydrogels with additional focus placed on the biomaterial applications of these materials.