Oxygen-mediated enzymatic polymerization of thiol–ene hydrogels

Abstract

Materials that solidify in response to an initiation stimulus are currently utilized in several biomedical and surgical applications; however, their clinical adoption would be more widespread with improved physical properties and biocompatibility. One chemistry that is particularly promising is based on the thiol–ene addition reaction, a radical-mediated step-growth polymerization that is resistant to oxygen inhibition and thus is an excellent candidate for materials that polymerize upon exposure to aerobic conditions. Here, thiol–ene-based hydrogels are polymerized by exposing aqueous solutions of multi-functional thiol and allyl ether PEG monomers, in combination with enzymatic radical initiating systems, to air. An initiating system based on glucose oxidase, glucose, and Fe²⁺ is initially investigated where, in the presence of glucose, the glucose oxidase reduces oxygen to hydrogen peroxide which is then further reduced by Fe²⁺ to yield hydroxyl radicals capable of initiating thiol–ene polymerization. While this system is shown to effectively initiate polymerization after exposure to oxygen, the polymerization rate does not monotonically increase with raised Fe²⁺ concentration owing to inhibitory reactions that retard polymerization at higher Fe²⁺ concentrations. Conversely, replacing the Fe²⁺ with horseradish peroxidase affords an initiating system is that is not subject to the iron-mediated inhibitory reactions and enables increased polymerization rates to be attained.