Dynamic Arrest and Tunable Gelation of Immunogenically Inert POEGMA Nanoparticles

Physically cross-linked hydrogels formed through noncovalent interactions offer reversible gelation, injectability, and shear-thinning behavior, making them ideal for biomedical applications. Temperature-responsive systems are particularly attractive, as they enable injection as a solution, and at physiological temperature for minimally invasive delivery. Poly-(oligo-(ethylene glycol) methacrylate) (POEGMA) is a promising nonimmunogenic polymer that combines PEG-like hydration and protein resistance with tunable thermal responsiveness that does not bind pre-existing anti-PEG antibodies that are ubiquitous and elicits a minimal antibody response against itself. Here, we show that diblock POEGMA copolymerscomposed solely of short ethylene glycol side chainsspontaneously self-assemble into nanoparticles and form physically cross-linked hydrogels above a controllable transition temperature, without chemical modification. Using fluorescence recovery after photobleaching and video particle tracking nanorheology, we identify a thermally induced transition from dynamically arrested viscoelastic hydrogels to dynamically arrested liquid coacervates. These results establish a new class of single-component, nonimmunogenic POEGMA hydrogels with tunable phase behavior and mechanical properties, offering a versatile platform for localized drug delivery, sustained release, and regenerative medicine.