Development of biocompatible dextran-oxanorbornadiene hydrogels

Abstract

Hydrogels have garnered much attention over the past few decades for their ability to deliver therapeutics with spatial and temporal control. However, many of these systems can exhibit burst release and are not easily adjusted to realize different release kinetics. The research reported in this thesis aims to develop tunable degradable hydrogels from oxanorbornadiene linkers, which have been shown to have programmable fragmentation rates that can be tuned over an exceptionally wide range of time. OND hydrogels of different crosslinking compositions were all able to form robust gels in as little as seconds and release of entrained cargo was found to be tunable over 0.5 to 25 days by changing the OND substitution or crosslinking system. Oxanorbornadiene hydrogels were then applied to in vivo models seeking to improve healing in chronic wounds where it was found that OND hydrogels were able to deliver therapeutic cargo at the expected preprogrammed rates to improve wound healing. Degradable hydrogels comprised of OND cleavable linkages continue to show great promise as simple drug delivery systems that can be widely useful to applications requiring controlled release over hours or months.