Reloadable Hydrogels Based on Triggered Loss of Multivalent Binding

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Bradley Smith of the University of Notre Dame aims to develop a new way to repeatedly load and release valuable molecular payloads from a hydrogel, which is a soft biocompatible material that also holds a large amount of water within its structure. The fundamental chemistry knowledge to be gained from this research is expected to have broad impact in three different hydrogel technologies that benefit society: (i) controlled release of pharmaceuticals from hydrogels for chemotherapy; (ii) controlled release of cell growth factors for tissue engineering and regenerative medicine and (iii) Controlled release of nutrients to maintain healthy biofilm factories for industrial-scale, cell-based manufacturing of commodity chemicals and fuels. There is also a complementary project to update the free internet workbook Organic Structure Elucidation: A Workbook of Unknowns which is used around the world by many instructors and students, especially those located in under-resourced educational environments. All activities will be conducted by a diverse group of graduate and undergraduate students who will be trained in experimental research at the interface of nanoscience, supramolecular chemistry, and macromolecular chemistry. The research aims to gain a deeper understanding of the thermodynamic and kinetic aspects of multivalent binding versus monovalent binding. This fundamental knowledge will be used to develop a generalizable, controlled-release platform that is based on a trivalent loader molecule with high affinity for the hydrogel interior. After hydrogel loading, the loader molecule will undergo a fragmentation process that simultaneously releases molecular payload and produces waste molecules that have weak hydrogel affinity and are readily displaced upon reloading with fresh loader molecule. A versatile synthetic method will enable the structure of the molecular payload on the loader molecule to be varied by a late-stage chemical reaction. The broad project goal is to demonstrate three sets of conceptually important thermodynamic and kinetic performance features, and this will be done by conducting experiments that measure the rate and extent of payload loading and release from hydrogels. The work will assess the impact of multivalency on the efficiency of hydrogel loading and release over multiple cycles. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.