(274a) Radical-Mediated Degradation of Thiol-Maleimide Adducts in Hydrogels

Michael addition reactions have been ubiquitously used in the synthesis of polymer networks, largely due to their speed, high conversion, and selectivity that enable tunability of network properties under a broad range of reaction conditions. Hydrogels are a specific class of polymeric materials often synthesized via Michael-type addition reaction, commonly leveraging the reaction of a thiolate end-group with the electron-deficient alkene of a maleimide. This reaction occurs under mild conditions necessary for applications such as tissue engineering, where crosslinking must often occur at physiological pH and temperature. While the simplicity of this chemistry enables facile synthesis of hydrogels with generally stable network structures, network degradation is also desirable in many instances. In this work, we report on the susceptibility of thiol-maleimide bonds to radical-mediated degradation. We demonstrate reversible degradation in crosslinked materials using photoinitiated and chemically initiated radicals in hydrogels, with the extent of degradation shown to be dependent on initiator concentration. We used linear polymer systems to identify degradation products, finding that radical-mediated degradation occurs at the thioether bond between the sulfur and beta carbon of the Michael adduct. Leveraging the spatial control of light, we used this degradation mechanism to demonstrate selective patterning of poly(ethylene glycol) (PEG)-based thiol-Michael hydrogels. These results illustrate the potential for radical-mediated degradation of thiol-maleimide polymers to be extended in a broad range of future applications.