New in situ crosslinking chemistries for hydrogelation

Over the last half century, hydrogels have found immense value as biomaterials in a vast number of biomedical and pharmaceutical applications. One subset of hydrogels receiving increased attention is in situ forming gels. Gelling by either bioresponsive self-assembly or mixing of binary crosslinking systems, these technologies are useful in minimally invasive applications as well as drug delivery systems in which the sol-to-gel transition aids the formulation's performance. Thus far, the field of in situ crosslinking hydrogels has received limited attention in the development of new crosslinking chemistries. Moreover, not only does the chemical nature of the crosslinking moieties allow these systems to perform in situ, but they contribute dramatically to the mechanical properties of the hydrogel networks. For example, reversible crosslinks with finite lifetimes generate dynamic viscoelastic gels with time-dependent properties, whereas irreversible crosslinks form highly elastic networks.; The aim of this dissertation is to explore two new covalent chemistries for their ability to crosslink hydrogels in situ under physiological conditions. First, reversible phenylboronate-salicylhydroxamate crosslinking was implemented in a binary, multivalent polymeric system. These gels formed rapidly and generated hydrogel networks with frequency-dependent dynamic rheological properties. Analysis of the composition-structure-property relationships of these hydrogels---specifically considering the effects of pH, degree of polymer functionality, charge of the polymer backbone and polymer concentration on dynamic theological properties---was performed. These gels demonstrate diverse mechanical properties, due to adjustments in the binding equilibrium of the pH-sensitive crosslinks, and thus have the potential to perform in a range of dynamic or bioresponsive applications.; Second, irreversible catalyst-free "click" chemistry was employed in the hydrogelation of multivalent azide-functionalized polymers with divalent electron-deficient alkyne crosslinkers. Elastic hydrogels formed at physiological temperature; however the gelation kinetics was found to be too slow for effective performance in most in situ crosslinking hydrogel applications. Therefore, a small molecule kinetics study using model crosslinking moieties was performed to evaluate the ability to expedite gelation via compositional changes in the alkyne dipolarophile. With further synthetic development, this crosslinking chemistry is likely to be useful in a number of applications requiring the formation of permanent, elastic networks in situ.