Post-Polymerization Programming of Polyurethane Thermogels with Tunable Gelation and Oxidation-Responsive Disassembly Behaviors

Abstract

Thermoresponsive injectable hydrogels based on amphiphilic block copolymers are widely explored as minimally invasive biomaterials, because they can be administered as sols and form gels in situ under physiological conditions. Among these systems, multiblock polyurethanes (PUs) are particularly versatile, owing to their step-growth synthetic flexibility, broad building block compatibility, and mechanically robust thermogelling networks. However, functional tuning in PU thermogels is commonly encoded during backbone construction, making the introduction of additional or orthogonal functionalities dependent on suitable building blocks and polymer redesign. Here, we report an atom transfer radical polymerization (ATRP)-enabled postpolymerization programming strategy in which responsive polymer segments are grown from an established PEG/PPG-based PU thermogel framework after backbone synthesis. The parent PU was converted into an ATRP macroinitiator and functionalized with poly(2-(methylthio)ethyl methacrylate) (PMTEMA) as a representative oxidation-responsive segment. Varying the PMTEMA content systematically regulated their assembly behaviors, gelation temperature, hydrogel stiffness, network morphology, and cargo release profile, while PMTEMA oxidation under H2O2 conditions promoted hydrogel destabilization and accelerated cargo release. Together with injectability and preliminary cytocompatibility, these results establish ATRP-mediated postpolymerization programming as a versatile route to expand the functionality of established PU thermogels without redesigning the parent thermogelling framework.